94157188 true A multicEntre trial to AssesS the validitY of the Kardia six-lead hand-held ECG in psychiatry (Easy ECG V1) Easy ECG V1 1. Compare the diagnostic accuracy of the K6L to the 12L for QT interval in people taking antipsychotic medication. 2. Compare the time to obtain QTc readings between the K6L and 12L – efficiency. 3. Understand the patient acceptability of the K6L compared with the 12L. 4. Using the NICE EVA as reference, determine why and how frequently it is necessary to perform a 12L after a K6L. 5. Describe the prevalence of QT prolongation in patients taking antipsychotics. 6. Understand the clinician acceptability of the K6L. Background and study aims Some medications that are prescribed for patients with mental health problems have side effects that can affect the heart. Doctors use heart tracings called ECGs to understand how the heart is working and ensure it is safe for the person to take these medications. To have a standard ECG, electrode stickers are stuck on the person's chest, wrists and ankles, who then needs to lie still whilst the ECG is recorded. Sometimes, people who need an ECG cannot have it. For example, people who are in distress may not be able to undress or lie still. Sometimes people feel uncomfortable undressing in front of others. Often, NHS clinics do not have the facilities to do ECGs, and the person's GP is asked to do it. Our work has shown that this causes delays in treatment and extra appointments. A new credit-card-sized ECG device (the Kardia 6L [K6L]) has recently been developed. To use it, the person rests two fingers on top of the device and places it so that the back touches the skin of their knee or ankle. The recordings are sent to a phone via Bluetooth. We think the K6L will help more people with mental illness get the ECGs they need. This would help improve safety for people taking medication, reduce the number of appointments and improve the experience for people. We have already shown that the K6L works well in patients seen in a cardiology service. We want to find out how well it works in people seen in mental health services. Who can participate? Patients aged 18 years and over who have been prescribed an antipsychotic medication in any setting What does the study involve? Once consented into the study, participants will first have their demographic information and relevant history recorded. This will be done by reviewing the patient records (notes) and speaking to the participant. Every participant will have their height and weight recorded. Participants will have a 12L ECG followed by a 6L ECG. The 6L should be started as soon as possible after the 12L ECG has been recorded. This time should be no longer than 2 minutes after the 12L has been recorded. The operator will be either a research assistant or a research nurse. At selected sites, a healthcare worker from the participant’s regular clinical team who has been trained to conduct ECGs will carry out the ECGs. The operator of the machines will record the time taken to conduct the 12L from the point that the participant starts to undress or the operator starts to prepare the equipment (whichever comes first). The operator will record the time taken to conduct a 6L starting from the time the operator starts to prepare the equipment. After the ECGs have been take the operator will ask the participant a two-question survey: If you were to have this procedure again with either machine, which test would you choose? What are the reasons you chose [answer from question 1]? What are the possible benefits and risks of participating? We do not anticipate any adverse events in this study. No intervention is being delivered, and data is being collected at one timepoint. Where is the study run from? Leeds Yorkshire Partnership Foundation Trust (UK) When is the study starting and how long is it expected to run for? April 2026 to April 2027 Who is funding the study? Alivecor, Inc. (USA) Who is the main contact? 1. Nazya Azam, nazya.azam@nhs.net 2. Dr George Crowther, georgecrowther@nhs.net QT interval Kardia 6L and standard 12-lead ECG baseline Old ethics approval format Approved 27/10/2025, HRA and Health and Care Research Wales (HCRW) (2 Redman Place, Stratford, London, E20 1JQ, UK; Tel: not available; approvals@hra.nhs.uk), ref: 25/YH/0173 10.1186/ISRCTN94157188 356658 CPMS: 61500 356658 61500 Non-randomized study Interventional Non randomised study Treatment 2027-04-01T00:00:00.000Z United Kingdom England Leeds and York Partnership NHS Foundation Trust

St. Marys House St. Marys Road

Leeds England LS7 3JX RGD@2.16.840.1.113883.2.1.3.2.4.18.48 Tees, Esk and Wear Valleys NHS Foundation Trust

Trust Headquarters West Park Hospital Edward Pease Way

Darlington England DL2 2TS RX3@2.16.840.1.113883.2.1.3.2.4.18.48 Kent and Medway Mental Health NHS Trust

Farm Villa Hermitage Lane

Maidstone England ME16 9PH RXY@2.16.840.1.113883.2.1.3.2.4.18.48 Essex Partnership University NHS Foundation Trust

The Lodge Lodge Approach Runwell

Wickford England SS11 7XX R1L@2.16.840.1.113883.2.1.3.2.4.18.48 Humber Teaching NHS Foundation Trust

Trust Hq Block a Willerby Hill Beverley Road Willerby

Hull England HU10 6ED RV9@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care NHS Foundation Trust

New Mill Victoria Road Saltaire

Shipley England BD18 3LD TAD@2.16.840.1.113883.2.1.3.2.4.18.48 Cambridgeshire and Peterborough NHS Foundation Trust

Elizabeth House Fulbourn Hospital Fulbourn

Cambridge England CB21 5EF RT1@2.16.840.1.113883.2.1.3.2.4.18.48 Surrey and Borders Partnership NHS Foundation Trust

18 Mole Business Park Randalls Road

Leatherhead England KT22 7AD RXX@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire and Isle of Wight Healthcare NHS Foundation Trust

Tatchbury Mount Hospital Calmore

Southampton England SO40 2RZ RW1@2.16.840.1.113883.2.1.3.2.4.18.48 false Any patient prescribed or due to be prescribed an antipsychotic medication in any setting (ward or outpatient) Mixed 18 Years 100 Years All 800 0 1. Aged under 18 years old 2. Patients who lack capacity and do not have a personal consultee to give advice or where the personal consultee does not think they would want to take part 2025-12-04T00:00:00.000Z 2027-04-01T00:00:00.000Z Cardiovascular and mental health Circulatory System We will conduct a multi-centre study comparing K6L vs 12L ECGs in people receiving antipsychotic therapy. There will be ten NHS sites in total. Our sites span England and Wales and serve a range of rural, urban and semi-rural communities. This will allow us to ensure participants are from a wide range of socioeconomic and ethnic backgrounds. Duration is eighteen months in total (3 months set up, 12 months data collection, 3 months analysis and write up). Recruitment will take place in any clinical area where antipsychotic treatments are prescribed (outpatient or inpatient) in eligible people. Study procedures consist of one 12L ECG and one KardiaMobile 6L ECG per participant, recorded sequentially by the same individual. The 6L should be started as soon as possible after the 12L ECG has been recorded. This time should be no longer than 2 minutes after the 12L has been recorded. Once consented into the study, participants will first have their demographic information and relevant history recorded. This will be done by reviewing the patient records (notes) and speaking to the participant. Demographic information: 1. Age 2. Gender at birth 3. Ethnicity 4. Height 5. Weight History: 1. Primary psychiatric diagnosis for which the antipsychotic is prescribed for 2. Other psychiatric diagnoses 3. Current antipsychotic treatment – type/types of antipsychotic, dose and administration route 4. Other prescribed medications that can impact QT interval 5. Cardiovascular history The 12L will be collected using a MAC 550 (GE Healthcare, WI, USA) or equivalent recorder (calibrated as per machine standards). The 6L will be collected using an Alivecor Kardiamobile 6-lead ECG machine. The operator will be either a research assistant or research nurse. At selected sites (Leeds, Hull, Tees Esk and Wear Valleys (TEWV) and Kent), a healthcare worker from the participant's regular clinical team who has been trained to conduct ECGs will carry out the ECGs. The operator of the machines will record the time taken to conduct the 12L from the point that the participant starts to undress or the operator starts to prepare the equipment (whichever comes first). The operator will also record the time taken to conduct a 6L starting from the time the operator starts to prepare the equipment. After the ECGs have been take the operator will ask the participant a two-question survey: 1. If you were to have this procedure again with either machine, which test would you choose? 2. What are the reasons you chose the [answer from question 1]? Participant survey data will be analysed to understand patient acceptability. A simple count will be used to demonstrate preference between the devices (survey question 1). Content analysis will be used to illustrate the reasons behind this decision and a list of the top 5 reasons for the preference will be created for each type of machine. Healthcare worker time to treatment and ECG quality analysis: At selected sites (Leeds, Kent, Hull and TEWV), 80 ECGs will be collected by a member of the participant's usual treating team who has been trained to use K6L and 12L ECGs. This is to test whether there is a difference in time taken to complete the ECGs and the K6L ECG quality when ECGs are completed by a researcher compared to the usual treating team (real world setting). The data recorded will be identical to the data collection set out above, except that the person conducting the ECG will be asked to indicate which ECG they prefer and why (objective 6). The ECGs will be graded by independent observers who are blinded to the patient and patient details. Noise on ECG will be described according to a noise score (NS) where NS 1 is a completely clear ECG, NS 2 is an ECG with noise but where a good interpretation was possible, NS 3 borderline ECG for noise (analysis based on RR regularity), and NS 4 is not interpretable. K6L validation: The automated QT and QTc analysis will be recorded. This data will be available to the clinical team to aid patient management. Additionally, all other automated intervals will be recorded, e.g. PR interval. Statistical analysis will be performed (Bland Altman and regression analysis) to compare the differences in these results between the 12L versus the K6L for QT, QTc and PR intervals in leads I, II, and AvL. Equivalence of the measurements using the two methods will be carried out using standard equivalence testing methods at a 5% level of significance, with 95% limits of agreement reported. Time to obtain ECG reading: Statistical analysis will be performed to compare the time taken to complete the 6- and 12-lead ECGs. Two separate analyses will be reported: 1. The difference in time when the ECGs are performed by a research assistant. 2. The difference in time when the ECGs are performed by a member of the clinical team (who has been trained to conduct ECGs). Frequency of the need to repeat ECG following K6L: From the 6L data only, using the NICE early valuation assessment criteria for when a repeat QT interval measurement using a 12-lead electrocardiogram (ECG) device is offered following a 6-lead ECG*, we will report the number and proportion of times it would be necessary to complete a 12 Lead ECG following a 6-lead ECG. *When QTc interval is > 440 in men or >470 in women. Prevalence of QT prolongation: The whole cohort will be used to demonstrate the prevalence of QT prolongation in (>440 in men, >470 in women) in people taking antipsychotics. We will also use the data to demonstrate any dose-related effects of antipsychotics on QT (total daily antipsychotic dose as an equivalent to haloperidol vs QTc), and any differences in QTc dependant on antipsychotic type or administration route. All prevalence data will be displayed as a percentage. Recruitment: Potential participants will be identified by their clinical care team, in conjunction with local site research assistants or research nurse (depending on site preference). A research assistant or research nurse (depending on site preference) at each site will recruit 80 participants from both wards and outpatient clinics. The research assistant/nurse will provide the participant information sheet and explain the study. We will work with our PPI group to ensure these materials are understandable and provide easy read versions. Furthermore, we have budgeted for services to translate patient information where necessary. It is hoped that participants will be recruited on the same day, but where necessary they will be given time to consider participation or discuss it with family and friends. Where potential participants lack capacity to consent, personal consultees will be approached on their behalf. Patients who do not wish to participate will receive treatment as usual. ECG registry: Every recruited patient will have the opportunity to opt into a long-term registry. Consent will be obtained to enable the study team to collect adverse cardiac event data and details of the psychotropic prescriptions from hospital or GP records for 10 years. Other Data sharing statement to be made available at a later date 77a68d28-9476-4e3d-9bd5-7e3e6d15a7ec 8b50210b-6e32-4731-9612-ee1882789b29 81826f35-0404-45cc-9d0b-18bac5540999 74e2c6f7-2959-4fd6-86be-20464f387187 No Nazya Azam Scientific

Leeds and York Partnership NHS Foundation Trust, 1st Floor, Main House, St Mary's House

Leeds United Kingdom LS7 3JX +44 (0)7980 958984 nazya.azam@nhs.net Public George Crowther Scientific

Liaison Psychiatry for Older People, Beckett Wing, St James's Hospital

Leeds United Kingdom LS9 7TF +44 (0)7703288239 georgecrowther@nhs.net Public Leeds and York Partnership NHS Foundation Trust Hospital/treatment centre https://ror.org/00n635c12 Non-commercial Alivecor, Inc. 79794378 true COmBining memantine And cholinesterase inhibitors in Lewy body dementia Treatment trial COBALT What is the clinical and cost effectiveness of memantine compared to placebo in patients with DLB (COBALT-DLB) and PDD (COBALT-PDD) who are being treated with an acetylcholinesterase inhibitor (donepezil, rivastigmine or galantamine)? Clinical effectiveness is determined using a global outcome scale - the Clinical Global Impression of Change (CGIC), 6 months after recruitment. Cost effectiveness will be measured using health economic indicators, in particular the Client Services Receipt Inventory which has been adapted for use specifically for the COBALT trial and looks at the participant's use of health and social care services. The secondary and exploratory objectives include determining whether active treatment with memantine vs. placebo leads to changes in: 1. Carer-based impression of global changes (using an adapted CGIC) 2. Cognitive function 3. Neuropsychiatric symptom frequency and severity 4. Quality of life and function for the patient 5. Quality of life for the care-giver 6. Long-term changes in global outcomes Background and study aims Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are related complex illnesses with a wide range of distressing symptoms. People with DLB/PDD have worse quality of life, more complex symptoms, higher care costs, and are more sensitive to medications than people with Alzheimer’s disease (AD). Acetylcholinesterase Inhibitors (AChEI) are commonly used medicines that can help people with DLB/PDD by improving day to day functioning and thinking abilities. Another drug which might help is memantine, used to treat moderate to severe confusion in AD. It may help to improve memory, awareness and the ability to perform daily functions; however, it is not clear if adding memantine to AChEI is beneficial for people with DLB/PDD. The aim of this trial is to find out if adding memantine to AChEI improves overall health and functioning for people with DLB or PDD. COBALT is a double-blind, placebo-controlled, randomised trial to assess the clinical and cost-effectiveness of memantine compared to placebo in patients on an AChEI with DLB (COBALT-DLB) and PDD (COBALT-PDD). There are two separate COBALT trials being carried out using the same protocol, one in the UK and one in Australia. We plan to recruit a total of 372 patients and their caregivers/informants. The UK trial will recruit 300 participants from 30 sites and the Australian trial will recruit 72 participants from up to 5 sites. UK and Australian data will be combined for analysis. Who can participate? Patients aged 55 years or older with DLB or PDD, and their caregivers/informants. What does the study involve? DLB/PDD patients aged ≥55 years with a Mini Mental State Examination score of ≥8, on a stable dose of AChEI will be randomised 1:1 to memantine or placebo for either 26 or 52 weeks. Both trials are identical in procedure and conduct, with the only variation being the disease group. Participants and their caregiver/informant will complete assessments at baseline, 26 weeks (primary, secondary and exploratory outcomes) and 52 weeks (secondary and exploratory outcomes). During these visits assessments will be completed by the patient and their caregiver /informant. What are the possible benefits and risks of participating? Benefits: The COBALT trial may help to improve treatment for people with DLB and PDD. The patients who participate in the trial may gain significant satisfaction from contributing and the regular contact from the local trial team. Risks: Memantine is well tolerated in patients with moderate to severe dementia in Alzheimer's Disease, with adverse events (AEs) reported in 10% of patients (comparable to placebo). The most frequently occurring adverse reactions are dizziness, headache, constipation, somnolence, and hypertension. Patients will undergo a titration phase in the first 4 weeks of their participation to assess how well they tolerate the IMP. At some visits the questionnaires and memory testing may take 1-2 hours. Participants may find the questions tiring, tedious or embarrassing. Participants may choose not to answer any specific questions or do any test at any time. We will ensure there are adequate rest breaks, however participants or their caregiver /informant can also request a break at any time. If the patient/caregiver requests an extended break, the assessments can be paused but must be resumed within 7 days of the initial visit. Where is the study run from? UK Trial - Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust (UK) Australian Trial - The University of Melbourne (UoM) When is the study starting and how long is it expected to run for? March 2022 to June 2027 Who is funding the study? NIHR Health Technology Assessment programme in the UK and National Health Medical Research Council in Australia. Who is the main contact? Sarah Dunn (UK), cobalt.study@ncl.ac.uk Cassandra Yankoff (Australia), dementiacentretrials@mh.org.au Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) scale at 26 and 52 weeks post baseline COBALT-DLB and COBALT-PDD at baseline, 26 and 52 weeks: 1. Caregiver/Informant Impression of Change (C/I-CGIC) 2. Montreal Cognitive Assessment (MoCA) 3. Neuropsychiatric Inventory Plus (NPI+) 4. Quality of life: EuroQol EQ-5D 5 Level (EQ-5D-5L) - patient 5. Quality of life: EQ-5D-5L – proxy 6. Hospital and Anxiety Depression Scale (HADS) 7. Disability Assessment for Dementia (DAD) 8. Impact of memantine on motor function: The Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III (MDS UPDRS-III 9. Epworth Sleepiness Scale (ESS) 10. Client Service Receipt Inventory (CSRI) 11. Zarit Burden Interview (ZBI) - Caregiver/informant 12. WHO Quality of Life - BREF Ethics approval required East of England - Essex Research Ethics Committee

The Old Chapel, Royal Standard Place

Nottingham United Kingdom NG1 6FS 22/EE/0075 Royal Melbourne Hospital

Grattan Street

Parkville Australia 3050 2023.031 10.1186/ISRCTN79794378 2021-003232-88 1004660 CPMS: 51602, RES-20-041, ERM ID 79783 2021-003232-88 1004660 51602 RES-20-041, ERM ID 79783 Interventional double-blind randomized parallel group placebo-controlled trial Interventional Randomised parallel trial Treatment 2027-06-30T00:00:00.000Z United Kingdom England Northern Ireland Scotland Australia The Newcastle upon Tyne Hospitals NHS Foundation Trust

Freeman Hospital Freeman Road High Heaton

Newcastle upon Tyne England NE7 7DN RTD@2.16.840.1.113883.2.1.3.2.4.18.48 South London and Maudsley NHS Foundation Trust

Bethlem Royal Hospital Monks Orchard Road

Beckenham England BR3 3BX RV5@2.16.840.1.113883.2.1.3.2.4.18.48 Cambridgeshire and Peterborough NHS Foundation Trust

Elizabeth House, Fulbourn Hospital Fulbourn

Cambridge England CB21 5EF RT1@2.16.840.1.113883.2.1.3.2.4.18.48 Essex Partnership University NHS Foundation Trust

The Lodge Lodge Approach Runwell

Wickford England SS11 7XX R1L@2.16.840.1.113883.2.1.3.2.4.18.48 Norfolk and Suffolk NHS Foundation Trust

Hellesdon Hospital Drayton High Road

Norwich England NR6 5BE RMY@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire and Isle of Wight Healthcare NHS Foundation Trust

Tatchbury Mount Hospital Calmore

Southampton England SO40 2RZ RW1@2.16.840.1.113883.2.1.3.2.4.18.48 Queen Elizabeth University Hospital

1345 Govan Road

Glasgow Scotland G51 4TF G405H@2.16.840.1.113883.2.1.3.8.2.16.2 Sussex Partnership NHS Foundation Trust

Trust Hq Swandean Arundel Road

Worthing England BN13 3EP RX2@2.16.840.1.113883.2.1.3.2.4.18.48 Devon Partnership NHS Trust

Wonford House Hospital Dryden Road

Exeter England EX2 5AF RWV@2.16.840.1.113883.2.1.3.2.4.18.48 North Bristol NHS Trust

Southmead Hospital Southmead Road Westbury-on-trym

Bristol England BS10 5NB RVJ@2.16.840.1.113883.2.1.3.2.4.18.48 Sheffield Health & Social Care NHS Foundation Trust

Fulwood House Old Fulwood Road

Sheffield England S10 3TH TAH@2.16.840.1.113883.2.1.3.2.4.18.48 Tees, Esk and Wear Valleys NHS Foundation Trust

Trust Headquarters West Park Hospital Edward Pease Way

Darlington England DL2 2TS RX3@2.16.840.1.113883.2.1.3.2.4.18.48 Cornwall Partnership NHS Foundation Trust

Carew House Beacon Technology Park Dunmere Road

Bodmin England PL31 2QN RJ8@2.16.840.1.113883.2.1.3.2.4.18.48 NHS Fife

Hayfield House Hayfield Road

Kirkcaldy Scotland KY2 5AH SF999@2.16.840.1.113883.2.1.3.8.2.16.1 Nottinghamshire Healthcare NHS Foundation Trust

The Resource, Trust Hq Duncan Macmillan House Porchester Road

Nottingham England NG3 6AA RHA@2.16.840.1.113883.2.1.3.2.4.18.48 NHS Lothian

Waverley Gate 2-4 Waterloo Place

Edinburgh Scotland EH1 3EG SS999@2.16.840.1.113883.2.1.3.8.2.16.1 Surrey and Borders Partnership NHS Foundation Trust

18 Mole Business Park Randalls Road

Leatherhead England KT22 7AD RXX@2.16.840.1.113883.2.1.3.2.4.18.48 South West London and St George's Mental Health Trust

Livingston House, 2-6 Queens Road, Teddington

London England TW11 0LX University College London Hospitals NHS Foundation Trust

250 Euston Road

London England NW1 2PG RRV00@2.16.840.1.113883.2.1.3.2.4.18.48 Kent and Medway Mental Health NHS Trust

Farm Villa Hermitage Lane

Maidstone England ME16 9PH RXY@2.16.840.1.113883.2.1.3.2.4.18.48 Oxford Health NHS Foundation Trust

Warneford Hospital Warneford Lane Headington

Oxford England OX3 7JX RNU@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care Trust

New Mill Victoria Road

Shipley England BD18 3LD Y04099@2.16.840.1.113883.2.1.3.2.4.18.48 Belfast Health and Social Care Trust

Trust Headquarters A Floor - Belfast City Hospital Lisburn Road

Belfast Northern Ireland BT9 7AB A3X4A@2.16.840.1.113883.2.1.3.2.4.18.48 Sherwood Forest Hospitals NHS Foundation Trust

Kings Mill Hospital Mansfield Road

Sutton-in-ashfield England NG17 4JL RK5@2.16.840.1.113883.2.1.3.2.4.18.48 Northern Care Alliance NHS Foundation Trust

Fairfield General Hospital Northern Care Alliance NHS Foundation Trust Rochdale Old Road Bury

Manchester England BL9 7TD The Walton Centre NHS Foundation Trust

Lower Lane Fazakerley

Liverpool England L9 7LJ RET20@2.16.840.1.113883.2.1.3.2.4.18.48 Lancashire and South Cumbria NHS Foundation Trust

Research and Development, Lantern Centre, Vicarage Lane, Fulwood

Preston England PR2 8DW Derbyshire Healthcare NHS Foundation Trust

Trust Headquarters Kingsway Hospital Kingsway

Derby England DE22 3LZ RXM@2.16.840.1.113883.2.1.3.2.4.18.48 Walter and Eliza Hall Institute (WEHI)

1G, Royal Parade

Parkville Australia VIC 3052 Patient Current inclusion criteria as of 21/12/2023: 1. Patients with a diagnosis or clinical features consistent with established consensus criteria for probable DLB or probable PDD 2. Aged ≥55 years 3. MMSE score ≥8. Evidence of mild, moderate, or moderate to severe cognitive impairment on similar global cognitive scales previously completed by their clinical care team (e.g., Addenbrooke’s Cognitive Examination, Mini-Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment) can be used to pre-screen the patient, prior to approach. 4. Receiving a stable dose of AChEI for ≥12 weeks prior to baseline, with no expected plans for dose adjustment during the trial period; dose adjustment will be allowed during the trial, if clinically indicated, following discussion with PI and, if required, the central trial team 5. If receiving any antiparkinsonian treatment, antidepressants, anxiolytics, antipsychotics, or other drugs with significant psychotropic effects then dose must be stable for a minimum of 4 weeks prior to enrolment with no expected plans for dose adjustment during the trial period. Dose adjustment will be allowed during the trial if clinically indicated and will be documented. If a change in medication with psychotropic effects is required, this decision can be made by the treating clinician (e.g., starting an antidepressant in clinic) without consultation with the CI. In some instances, the clinician may feel it is appropriate/relevant to discuss this with the PI prior to prescribing, for example, if the clinician feels that the medication change may have an impact on the trial and/or trial medication. Any changes should however be documented in the patient’s concomitant medications electronic Case Report Form (eCRF). 6. Patients who lack capacity will be required to have a personal/professional nominated representative who is able to give informed consent on the patient’s behalf 7. Females must be postmenopausal and not receiving IVF treatment or must have undergone permanent sterilisation. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 8. Patients with sufficient knowledge of the English language or support to understand the Patient Information Sheet and complete the trial assessments _____ Previous inclusion criteria: 1. Patients with a diagnosis or clinical features consistent with established consensus criteria for probable DLB or probable PDD. 2. Aged ≥50. 3. MMSE score ≥ 8.* 4. Receiving a stable dose of AChEI for ≥12 weeks prior to baseline, with no expected plans for dose adjustment during the trial period; dose adjustment will be allowed during the trial, if clinically indicated, following discussion with PI and, if required, the central trial team. 5. If receiving any antiparkinsonian treatment, antidepressants, anxiolytics, antipsychotics, or other drugs with significant psychotropic effects then dose must be stable for a minimum of 4 weeks prior to enrolment with no expected plans for dose adjustment during the trial period. † 6. Patients who lack capacity will be required to have a personal/professional nominated representative who is able to give informed consent on the patient’s behalf. 7. 7. Females must be postmenopausal and not receiving IVF treatment or must have undergone permanent sterilisation†† 8. Patients with sufficient knowledge of the English language or support to understand the Patient Information Sheet and complete the trial assessments *Evidence of mild, moderate, or moderate to severe cognitive impairment on similar global cognitive scales previously completed by their clinical care team (e.g., Addenbrooke’s Cognitive Examination, Mini-Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment) can be used to pre-screen the patient, prior to approach. †If a change in medication with psychotropic effects is required, this decision can be made by the treating clinician (e.g., starting an antidepressant in clinic) without consultation with the CI. In some instances, the clinician may feel it is appropriate/relevant to discuss this with the PI prior to prescribing, for example, if the clinician feels that the medication change may have an impact on the trial and/or trial medication. Any changes should however be documented in the patient’s concomitant medications electronic Case Report Form (eCRF). ††Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Mixed 55 Years 99 Years All 300 0 1. Atypical clinical features or course suggestive of an alternative dementia diagnosis. 2. Any clinically relevant concomitant disease that will affect ability to participate in the trial including, but not limited to, chronic renal disease stage 5, history of acute or chronic pancreatitis, epilepsy or former history of convulsions, patients with recent myocardial infarction (within last 6 months), uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension. 3. Patients with severe hepatic impairment based on known history and/or significant abnormalities identified in blood liver function tests (for example, levels in liver function tests that are 2-3 times higher than the upper limit of normal), which in the judgement of the local PI would exclude the patient from the trial.* 4. Patients taking memantine, amantadine, ketamine, or dextromethorphan. 5. Any neurological or major psychiatric diagnosis that may be contributing to cognitive impairment above and beyond that caused by the patients DLB or PDD. 6. Renally impaired patients with eGFR <35 mL/min/1.73m².† 7. Currently taking part in another clinical trial that would interfere with the outcomes of the COBALT trial. 8. If in the opinion of the investigator, the patient would be unable to comply with the trial procedures or has difficulty taking oral medications. 9. Patients without a reliable caregiver/informant. *LFTs should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. †U&Es should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. For example, a borderline eGRF <45 mL/min/1.73m². 2022-11-24T00:00:00.000Z 2026-10-31T00:00:00.000Z Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) Nervous System Diseases Current interventions as of 21/04/2026: Memantine will be the Investigational Medicinal Product (IMP) for the COBALT trials. Memantine is currently licensed for the treatment of moderate to severe dementia in Alzheimer’s disease and is used off-licence in the UK for treatment of other dementias including DLB and PDD. IMP: Memantine 10mg tablets and Memantine 5mg tablets (Oral capsules). Placebo: Matched placebo tablets for memantine 5mg and 10 mg tablets will be manufactured and classed as an IMP for this trial (Oral capsules). All participants will receive an initial 4-week titration pack with clear instructions stated in the participant diary (part 1) dose instructions table. This table must be completed by the local trial team and the participant must be in receipt of the diary prior to starting the IMP. The 4-week titration schedule will start at 5mg daily in a single dose, taken in the morning. Thereafter, the dose will be increased by 5mg every week. The target dose will be 20mg/day, taken in the morning but titration will be based on tolerability and response. Potentially eligible patients will attend a screening visit during which consent will be obtained prior to any eligibility checks and the trial eligibility confirmation will be performed. This will include review of Liver and kidney function tests within the preceding 6 months. If no test results are available within this timeframe, a blood sample will be required to carry out these tests. A Mini Mental State Examination (MMSE) will be completed with the patient and a clinical diagnostic worksheet will be completed to confirm the patient’s diagnosis (Dementia with Lewy Bodies or Parkinson’s Disease Dementia). The patients will also be required to have a caregiver/informant in order to be eligible for the trial. The patient’s caregiver/informant should be a person that is in regular contact with the patient, who knows the patient well and is able to attend the trial follow-up visits as required. The caregiver/informant will complete assessments relating to the patient and themselves during the scheduled trial visits. The caregiver/informant should be identified during the screening process and is required to consent to take part in the COBALT trial. Once the patient has been consented and confirmed eligible, they will be randomised as a participant in either the COBALT – DLB or COBALT – PDD module of the trial, depending on their diagnosis confirmed at screening. For each trial module, a central, secure, web-based randomisation system with concealed allocation (Sealed Envelope – UK; REDCap – Aus)) will assign participants to active or placebo treatment in a 1:1 ratio. All participants, their caregiver/informants and site staff will be blinded to the participants treatment allocation, meaning that they will not know if the participant is receiving active or placebo treatment. The baseline assessments can be carried out once the participant has been consented, screened and randomised. This can occur at the same visit or can be scheduled for another day, within 14 days of the consent and screening visit. At baseline the primary, secondary, and exploratory outcome assessments will be conducted. IMP will be dispensed, along with the participant diary to record any adverse events, missed trial medication, visits to health care professionals and changes to concomitant medications. The participants and their caregiver/informant will also be given a participant safety card that includes information relating to their participation and emergency contact numbers for the trial team. Participants will be instructed to carry the card at all times and present it to any healthcare professional that they see during their COBALT trial participation. Following the participants initial baseline visit a number of follow up visits are required. Visit 5 (week 26) - These visits may occur at the local trial site, in the participant’s home. The primary, secondary and exploratory outcome assessments will be conducted per protocol section 7.4.2. IMP will be dispensed, IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. For participants receiving 26 weeks of IMP, this will be their final in-person visit. Visit 7 (week 52)/Early Withdrawal - These visits may occur at the local trial site, in the participant’s home. Secondary and exploratory outcomes will be conducted per protocol section 7.4.3. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. Only participants receiving 52 weeks of IMP will have this visit at 52 weeks. Visit 2 (week 3), Visit 3 (week 8), Visit 4 (week 14) and Visit 6 (week 38) - These visits may occur at the local trial site, in the participant’s home or by telephone/video call. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications per protocol section 7.4.4. At visit 4 and visit 6 IMP will be dispensed to ensure a continued supply for the participant. Only participants receiving 52 weeks of IMP will have visit 6 at week 38. A Resolution Call will be made to participants 4 weeks after discontinuation of IMP. This will normally be at week 56 (Visit 8) or at week 30 for those receiving 26 weeks of IMP. This call is to document any adverse events they have experienced following discontinuation of IMP Participants are given the option to consent to a long-term follow up 12 months after the end of their participation in the trial. This can either be by review of the medical records or by speaking to someone from the local or central trial team, depending on what the participant agrees to. The purpose of this additional follow-up is to understand the long-term outcomes for patients with DLB and PDD following treatment with memantine. At selected UK trial sites, participant consent will be obtained to collect and store approximately 30mL of blood for future research. This will be collected at a single timepoint and can be done at any point during the trial. Participants who have already completed the trial may also be approached about donating a sample. At selected Australian trial sites, participant consent will be obtained to collect and store approximately 60mL of blood for future research including for example biomarker development, genomics, transciptomics. Blood may be collected at up to 3 timepoints throughout the trial i.e. baseline, week 26 and week 52. _____ Previous interventions: Memantine will be the Investigational Medicinal Product (IMP) for the COBALT trials. Memantine is currently licensed for the treatment of moderate to severe dementia in Alzheimer’s disease and is used off-licence in the UK for treatment of other dementias including DLB and PDD. IMP: Memantine 10mg tablets and Memantine 5mg tablets (Oral capsules). Placebo: Matched placebo tablets for memantine 5mg and 10 mg tablets will be manufactured and classed as an IMP for this trial (Oral capsules). All participants will receive an initial 4-week titration pack with clear instructions stated in the participant diary (part 1) dose instructions table. This table must be completed by the local trial team and the participant must be in receipt of the diary prior to starting the IMP. The 4-week titration schedule will start at 5mg daily in a single dose, taken in the morning. Thereafter, the dose will be increased by 5mg every week. The target dose will be 20mg/day, taken in the morning but titration will be based on tolerability and response. Potentially eligible patients will attend a screening visit during which consent will be obtained prior to any eligibility checks and the trial eligibility confirmation will be performed. This will include review of Liver and kidney function tests within the preceding 6 months. If no test results are available within this timeframe, a blood sample will be required to carry out these tests. A Mini Mental State Examination (MMSE) will be completed with the patient and a clinical diagnostic worksheet will be completed to confirm the patient’s diagnosis (Dementia with Lewy Bodies or Parkinson’s Disease Dementia). The patients will also be required to have a caregiver/informant in order to be eligible for the trial. The patient’s caregiver/informant should be a person that is in regular contact with the patient, who knows the patient well and is able to attend the trial follow-up visits as required. The caregiver/informant will complete assessments relating to the patient and themselves during the scheduled trial visits. The caregiver/informant should be identified during the screening process and is required to consent to take part in the COBALT trial. Once the patient has been consented and confirmed eligible, they will be randomised as a participant in either the COBALT – DLB or COBALT – PDD module of the trial, depending on their diagnosis confirmed at screening. For each trial module, a central, secure, web-based randomisation system with concealed allocation (Sealed Envelope – UK; REDCap – Aus)) will assign participants to active or placebo treatment in a 1:1 ratio. All participants, their caregiver/informants and site staff will be blinded to the participants treatment allocation, meaning that they will not know if the participant is receiving active or placebo treatment. The baseline assessments can be carried out once the participant has been consented, screened and randomised. This can occur at the same visit or can be scheduled for another day, within 14 days of the consent and screening visit. At baseline the primary, secondary, and exploratory outcome assessments will be conducted. IMP will be dispensed, along with the participant diary to record any adverse events, missed trial medication, visits to health care professionals and changes to concomitant medications. The participants and their caregiver/informant will also be given a participant safety card that includes information relating to their participation and emergency contact numbers for the trial team. Participants will be instructed to carry the card at all times and present it to any healthcare professional that they see during their COBALT trial participation. Following the participants initial baseline visit a number of follow up visits are required. Visit 5 (week 26) - These visits may occur at the local trial site, in the participant’s home. The primary, secondary and exploratory outcome assessments will be conducted per protocol section 7.4.2. IMP will be dispensed, IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. Visit 7 (week 52)/Early Withdrawal - These visits may occur at the local trial site, in the participant’s home. Secondary and exploratory outcomes will be conducted per protocol section 7.4.3. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. Visit 2 (week 3), Visit 3 (week 8), Visit 4 (week 14) and Visit 6 (week 38) - These visits may occur at the local trial site, in the participant’s home or by telephone/video call. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications per protocol section 7.4.4. At visit 4 and visit 6 IMP will be dispensed to ensure a continued supply for the participant. A Resolution Call will be made to participants at week 56 (Visit 8) to document any adverse events they have experienced following the Visit 7 (week 52)/Early Withdrawal visit per protocol section 7.4.5. Participants are given the option to consent to a long-term follow up 12 months after the end of their participation in the trial. This can either be by review of the medical records or by speaking to someone from the local or central trial team, depending on what the participant agrees to. The purpose of this additional follow-up is to understand the long-term outcomes for patients with DLB and PDD following treatment with memantine. At selected Australian trial sites, participant consent will be obtained to collect and store approximately 60mL of blood for future research including for example biomarker development, genomics, transciptomics. Blood may be collected at up to 3 timepoints throughout the trial i.e. baseline, week 26 and week 52. Drug Phase III Memantine hydrochloride neuraxpharm 5 mg film-coated tablets, memantine Torrent 10 mg film-coated tablets The datasets generated during and/or analysed during the current study are/will be available upon request. We will provide a contact in due course but this is likely to be the Chief Investigator, Professor John – Paul Taylor. Available on request Protocol

Added from spreadsheet

Study website Migrated from study website field

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1-4 Claremont Terrace Newcastle Clinical Trial Unit Newcastle University

Newcastle Upon Tyne United Kingdom NE2 4AE +44 191 208 0423 cobalt.study@ncl.ac.uk Public Cassandra Yankoff Public

Watson/Yassi Laboratory Department of Population Health and Immunity Walter and Eliza Hall Institute of Medical Research (WEHI)

Parkville Australia - - dementiacentretrials@mh.org.au Public John-Paul Taylor Principal investigator

Campus for Ageing and Vitality

Newcastle upon Tyne United Kingdom NE4 5PL +44 191 2081311 john-paul.taylor@newcastle.ac.uk Public Rosie Watson Principal investigator

Walter and Eliza Hall Institute (WEHI)

Parkville Australia 3052 - watson.r@wehi.edu.au Public Cumbria Northumberland Tyne and Wear NHS Foundation Trust Hospital/treatment centre https://ror.org/01ajv0n48 Non-commercial University of Melbourne University/education Non-commercial Health Technology Assessment Programme http://dx.doi.org/10.13039/501100000664 National Health and Medical Research Council http://dx.doi.org/10.13039/501100000925