Understanding Brain Inflammation in Cognitive Problems (BRIC)
| ISRCTN | ISRCTN11195489 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11195489 |
| IRAS number | 305370 |
| Secondary identifying numbers | CPMS 54263 |
- Submission date
- 28/03/2024
- Registration date
- 09/07/2024
- Last edited
- 19/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Dementia with Lewy bodies (DLB) affects one hundred thousand people in the UK. The causes of DLB are not completely understood but it is expected that the immune system plays an important role, as it does with Alzheimer’s disease (AD). In AD, activation of the immune system is thought to happen years before the symptoms of dementia occur. This immune activation increases the risk of developing AD in later life. Also, events that activate the immune system in the blood, such as urine infections, are known to cause worsening of memory symptoms in people who already have AD. We do not yet know if the same is true in DLB.
We will measure inflammation in the body using blood tests to answer important questions such as:
1. Are cognitive problems associated with inflammation?
2. Is inflammation associated with the progression of cognitive problems?
Who can participate?
People aged 60 years and over with specific cognitive problems, along with people aged 60 years and over without cognitive problems.
What does the study involve?
All participants will have a clinical assessment and blood samples. The clinical assessment will help the researchers to understand the problems people are experiencing, and if their problems are progressing over time. Blood samples will show how inflammation in the body affects the brain. Participants will have a further clinical assessment and blood samples annually for 2 years. The findings of this study could identify inflammation as a new treatment target for people with cognitive problems.
What are the possible benefits and risks of participating?
There is no direct benefit from taking part in this study. However, the information from this study may help improve the future treatment of people with cognitive problems.
Where is the study run from?
University of Southampton (UK)
When is the study starting and how long is it expected to run for?
February 2020 to September 2029
Who is funding the study?
Lewy Body Society (UK)
Who is the main contact?
Dr Jay Amin, jay.amin@soton.ac.uk
Contact information
Public, Scientific, Principal Investigator
Memory Assessment and Research Centre (MARC), Tom Rudd Unit, Moorgreen Hospital, Botley Road
Southampton
SO30 3JB
United Kingdom
 ORCID ID |
0000-0003-3792-0428 |
|---|---|
| Phone | +44 (0)2380475206 |
| jay.amin@soton.ac.uk |
Study information
| Study design | Longitudinal observational case-control study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Understanding Brain Inflammation in Cognitive Problems (BRIC) |
| Study acronym | BRIC |
| Study objectives | Current Study hypothesis as of 16/05/2025: 1. MCI-LB/mild DLB will show an increased peripheral pro-inflammatory profile and increased immunosenescent profile at baseline compared to controls. 2. Increased immunosenescent markers at baseline will be associated with more rapid disease progression in MCI-LB/mild DLB. 3. More frequent occurrence of peripheral pro-inflammatory events (e.g. infections, surgery) will be associated with increased pro-inflammatory cytokines and more rapid disease progression in MCI-LB/mild DLB. _____ Previous Study hypothesis: 1. Mild cognitive impairment with Lewy bodies (MCI-LB)/mild dementia with Lewy bodies (DLB) will be associated with increased 18F-DPA714 binding, which will be associated with more rapid disease progression. 2. 18F-DPA714 binding will decline over time in MCI-LB/mild DLB. 3. MCI-LB/mild DLB will show an altered peripheral inflammatory profile at baseline compared to controls. 4. Alterations in immunosenescent markers at baseline will be associated with more rapid disease progression in MCI-LB/mild DLB. 5. More frequent occurrence of peripheral pro-inflammatory events (e.g. infections, surgery) will be associated with increased pro-inflammatory cytokines and more rapid disease progression in MCI-LB/mild DLB. |
| Ethics approval(s) |
Approved 15/11/2022, Wales REC 7 (St David's Park, Carmarthen, SA31 3HB, United Kingdom; +44 (0)2922 941107; Wales.REC7@wales.nhs.uk), ref: 22/WA/0312 |
| Health condition(s) or problem(s) studied | Dementia with Lewy bodies |
| Intervention | Current interventions as of 16/05/2025: At the initial baseline assessment, consent and clinical assessment will be carried out over two visits, each taking 1-2 hours. This will include a blood test. Follow-up will take place annually for 2 years. After 1 year, the researchers will contact study volunteers to see if they are happy to have an appointment to repeat some of the assessments, have a blood sample and repeat the questionnaires with a relative/friend, taking 1-2 hours. After 2 years, the researchers will contact study volunteers to see if they are happy to have clinical assessment, questionnaires and a repeat blood sample, taking 1-2 hours. _____ Previous interventions: At the initial baseline assessment, consent and clinical assessment will be carried out over two visits, each taking 1-2 hours. This will include a blood test. Most participants will have brain scans (a combined PET and MRI scan, or separate PET and MRI scans on different days, each taking 1-1.5 hours). Follow-up will take place annually for 2 years. After 1 year, the researchers will contact study volunteers to see if they are happy to have an appointment to repeat some of the assessments, have a blood sample and repeat the questionnaires with a relative/friend, taking 1-2 hours. After 2 years, the researchers will contact study volunteers to see if they are happy to have repeat brain imaging, clinical assessment, questionnaires and a repeat blood sample, taking 1-2 hours. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 16/05/2025: Peripheral blood inflammatory profile is measured by flow cytometry of cells and analysis of inflammatory markers at baseline, 1 year and 2 years. _____ Previous primary outcome measure: Brain Mitochondrial Translocator Protein (TSPO) is measured by 18F-DPA714 binding (mean cortical and regional) at baseline and 2 years |
| Secondary outcome measures | Current secondary outcome measures as of 16/05/2025: 1. Cognition is measured using the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at baseline, 1 year and 2 years. 2. Global functional impairment is measured using the Clinical Dementia Rating Scale Sum of Boxes at baseline, 1 year and 2 years. _____ Previous secondary outcome measures: 1. Peripheral blood inflammatory profile is measured by flow cytometry of cells and analysis of inflammatory markers at baseline, 1 year and 2 years 2. Cognition is measured using the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at baseline, 1 year and 2 years 3. Global functional impairment is measured using the Clinical Dementia Rating Scale Sum of Boxes at baseline, 1 year and 2 years |
| Overall study start date | 01/02/2020 |
| Completion date | 01/09/2029 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 60 Years |
| Upper age limit | 120 Years |
| Sex | Both |
| Target number of participants | 70 |
| Key inclusion criteria | MCI-LB/DLB group: 1. Age ≥60 years 2. Fulfil criteria for probable MCI-LB (McKeith et al., 2020) or DLB (McKeith et al., 2017) 3. Capacity to consent to participation in the study 4. MMSE ≥20 5. If on cholinesterase inhibitors and/or memantine, stable dose for 3 months Control group: 1. Age ≥60 years 2. MMSE ≥27 3. No evidence of mild cognitive impairment or dementia |
| Key exclusion criteria | 1. Active systemic inflammatory disease 2. Active autoimmune disease 3. Taking immune system modifying medications (e.g., oral steroids or tumour necrosis factor inhibitors) 4. Taking incretin analogues (e.g., liraglutide), minocycline or other microglial suppressing agents 5. History of clinical stroke 6. Current major depression 7. History of bipolar disorder, non-organic psychosis (e.g., longstanding schizophrenia) or recurrent severe depression 8. Chronic migraine |
| Date of first enrolment | 14/02/2024 |
| Date of final enrolment | 14/08/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Calmore
Southampton
SO40 2RZ
United Kingdom
Sponsor information
Hospital/treatment centre
University Road
Southampton
SO17 1BJ
England
United Kingdom
| Phone | +44 2380 595058 |
|---|---|
| rgoinfo@soton.ac.uk | |
| Website | http://www.southampton.ac.uk/ |
"ROR" |
https://ror.org/01ryk1543 |
Funders
Funder type
Charity
Government organisation / Associations and societies (private and public)
- Alternative name(s)
- The Lewy body Society, LBS
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | The results from this research will be shared with the wider research community through publication in high-impact journals in the fields of clinical medicine and medical imaging, and presentation at international conferences. The researchers will seek to disseminate their findings to the public through local, regional and/or international meetings. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository (https://www.dementiasplatform.uk/) |
Editorial Notes
19/05/2025: The following changes were made to the trial record:
1. Contact details updated.
2. The sponsor was changed from Newcastle upon Tyne Hospitals NHS Foundation Trust to University of Southampton.
3. The funder UK Research and Innovation Medical Research Council was removed.
16/05/2025: The following changes were made to the trial record:
1. The study hypothesis was changed.
2. The interventions were changed.
3. The primary outcome measure was changed.
4. The secondary outcome measures were changed.
5. The target number of participants was changed from 110 to 70 .
6. The study participating centres Newcastle upon Tyne Hospitals NHS Foundation Trust, Southern Health NHS Foundation Trust were removed and Hampshire and Isle of Wight Healthcare NHS Foundation Trust was added.
7. The plain English summary was updated to reflect these changes.
02/04/2024: Study's existence confirmed by Wales REC 7.
