Feasibility study: Can reducing periodontal infection (gum disease) slow the progression of cognitive impairment associated with Alzheimer's disease?
| ISRCTN | ISRCTN11832395 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11832395 |
| IRAS number | 315223 |
| Secondary identifying numbers | CPMS 53909, NIHR 203048, IRAS 315223 |
- Submission date
- 20/10/2022
- Registration date
- 31/10/2022
- Last edited
- 15/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Oral Health
Plain English summary of protocol
Background and study aims
Alzheimer’s disease has recently been linked to oral health and certain bacteria that are found in the mouth (oral bacteria). We want to see whether, with appropriate dental treatment we can improve Oral health (oral hygiene, how well we clean our teeth and gums) and reduce the number of oral bacteria in people living with memory loss. If the study is successful, we want to complete a bigger study to see if keeping teeth and gums clean can slow the progression of Alzheimer’s disease
Who can participate?
Adults aged 60+ years with Mild Cognitive Impairment (MCI) or early-stage Alzheimer's Disease (AD) and capacity to consent will be recruited to the study. As well as a diagnosis of AD or MCI, participants must have gum disease, which will be assessed at screening by a study dentist. As gum disease is very prevalent as we get older it is likely that most participants who are screened will have sufficient gum disease to qualify for study inclusion. Participants will be asked to have a study partner who can attend at least the first appointment when the capacity to consent is determined.
What does the study involve?
Eligible participants who give informed consent will be allocated at random to either the control or the treatment group. Control group participants will be told they have gum disease, provided with a gum health care leaflet and an electric toothbrush, and advised to attend their dentist, but will not receive study treatment. Treatment group participants will be given the same gum health leaflet and an electric toothbrush, and allocated to a dental practice for gum disease treatment delivered by specially trained dentists in a way that is personal to the participant.
Both study groups will assessed for cognition and gum health at screening, 6 and 12 months and samples of blood and saliva will be taken at these visits so that the bacterial load and levels of some inflammatory proteins can be monitored over the course of the study. At the 12-month appointment participants will be asked to take part in a short interview to gather their thoughts about the study. For participants who join the study at the start of recruitment there will be a final 18-month assessment of cognition. Participants in the control group will be offered study treatment after they have completed the study.
What are the possible benefits and risks of participating?
The dental treatment the participant will be given will be routine. Every effort will be made to alleviate any pain or discomfort with a dental cause. Risks of treatment will be no greater than those encountered when they attend an appointment with their own dentist.
When necessary, an injection to numb the mouth before treatment will be given to minimise any discomfort. A gel will be applied prior to the injection to minimise any discomfort from the injection itself.
The participant will be asked to have an X-ray to determine what treatment is needed. This is a normal requirement prior to dental treatment, and the dose of radiation that they receive from the X-ray is low. The X-rays will enable the dentist to spot problems and signs of disease that may not be visible on the surface of your teeth and gums when the dentist examines them. The X-rays are necessary to reach a diagnosis and formulate the best treatment plan.
If it is thought to be necessary, the participant will be asked to take a short course of antibiotics, and it is possible that they could be allergic to the antibiotic prescribed. The dentist will take a full medical history to make sure they are not prescribing something that they are known to be allergic to. They will also provide advice to the participant and project partner regarding what to do and who to contact if they feel unwell after taking the antibiotics. As with all antibiotics, there is a risk of gut problems which can cause symptoms whilst taking a course of antibiotics or up to 2 months afterwards. Noticeable symptoms may be changed bowel movements, diarrhoea, fever, loss of appetite, nausea, abdominal pain or tenderness. This can be caused by the bacteria Clostridium difficile and associated disease and if they notice any of these changes, they should arrange a consultation with their general medical practitioner (doctor).
When blood is taken there will be a sharp scratch from the needle, but this should not last long and is no different to giving blood for a blood test.
Where is the study run from?
University Hospitals Bristol and Weston NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
July 2022 to December 2025
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).
Who is the main contact?
Nikki Hellin, nikki.hellin@bristol.ac.uk
Contact information
Scientific
Dental Clinical Trials Unit
Bristol Dental School
Lower Maudlin Street
Bristol
BS1 2LY
United Kingdom
 ORCID ID |
0000-0002-9127-5530 |
|---|---|
| Phone | +44 7825831352 |
| n.x.west@bristol.ac.uk |
Public
Dental Clinical Trials Unit
Bristol Dental School
Lower Maudlin Street
Bristol
BS1 2LY
United Kingdom
| Phone | +44 7773579130 |
|---|---|
| nikki.hellin@bristol.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | See study outputs table |
| Scientific title | The Oral Health for Brain Health (Mysmile) Study |
| Study acronym | Mysmile |
| Study objectives | Most gum diseases are preventable and patients with active disease can be treated and returned to oral health. Therefore, stabilising gum health manages an important risk-factor for inflammatory diseases, including Alzheimer’s Disease (AD). This clinical study will test the feasibility of a large-scale trial aiming to demonstrate whether our intervention with intensive dental care for periodontitis, facilitating a lessening of bacteria-induced inflammation, can achieve oral health in AD patients and slow their AD-disease progression. |
| Ethics approval(s) | Approved 02/11/2022, West of Scotland Research Ethics Committee 5 (West of Scotland Research Ethics Service, Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE, UK; +44 (0)141 3140213; WoSREC5@ggc.scot.nhs.uk), ref: 22/WS/0137 |
| Health condition(s) or problem(s) studied | Oral and dental health, Alzheimer's disease |
| Intervention | At screening, consent will be taken by a researcher trained in taking informed consent from those suffering from memory loss, a project partner will be present at the screening appointment before capacity to consent has been confirmed. This researcher will then assess cognition and confirm cognitive eligibility scores and then the study dentist will conduct the dental assessment and confirm dental eligibility. This will take place at one site and in one appointment to minimise study visits. The study dentist or a member of the dental team qualified in venepuncture will take as sample of blood and ask participants to swish a mouthful of mouthrinse and expectorate into a pot. The dental team will then provide eligible participants with an electric toothbrush, interdental brushes and toothpaste and gum health leaflet, and details of how the participant would like to be contacted about the study will be collected. As confirmation of cognitive and dental scores is required for stratification eligible participants will not be told which group they have been randomised to on the day of screening as this would add too much time to the visit, instead they will be contacted by the means agreed the following day or after the weekend. Eligible participants will be randomised to control or treatment groups, and stratified so that each group has roughly equivalent numbers of individuals with MCI and mild periodontitis. When contacted regarding the group they have been randomised to, those in the control group will be encouraged to seek dental treatment, and reminded that they can get study treatment at the end if they would like it. Those randomised to the treatment group will be told which dental practice this will be in, and we will endeavour to identify a practice near to the participant. The practices who have agreed to deliver the dental treatment are those who provide training for newly qualified dental practitioners and are located in and around Bristol, a small number of participants will also be treated by clinicians on dental training pathways at Bristol Dental Hospital. The dentists in these practices/at the dental hospital will be trained by the Chief Investigator and senior study dentist, both periodontologists. They will also be on had to support the foundation dentists/specialty training pathway dentists as needed to ensure that the study treatment is carried out as planned. The dental intervention is based on standard treatment for periodontitis, but with a focus on the participant and comprises (1) Behaviour motivation and support for participants to attain and maintain effective plaque removal and reduce gum inflammation by a personalised, tailored oral hygiene regimen and motivational advice to maximise home-compliance (2) the reduction/elimination of plaque and calculus below the gum line with standard mechanical therapies and antibiotics if indicated clinically, (3) further treatment of any oral sites that respond poorly to initial treatment, (4) provision of supportive periodontal care per 2021 UK-guidelines to maintain oral health. This treatment will take on average 3 appointments within the first 3-4 months, but could require more visits as it is dependent on how well the participant responds to the treatment and is able to undertake oral hygiene at home. Participants in the treatment group will be made aware of the potential number of visits. Participants in the treatment group will also be sent motivational communications about aspects of oral hygiene to help remind them about taking care of their gums. All participants will be asked to return to the Brain Centre at Southmead Hospital 6 and 12 months after their screening appointment for further memory and dental assessments and give further samples of blood and saliva. At the 12-month appointment participants will be approached to take part in a short interview to gain their feedback about their experience of taking part in the study. This will be audio recorded. After 18 months those who are recruited at the start of the study will be invited to have one final cognitive assessment. It is anticipated that this might be via a zoom link or similar as the cognitive assessors used remote assessments successfully during the pandemic, and this will avoid the need to travel, but can be in person if the participant prefers. This additional 18 month time point was requested by the funder, but they acknowledged that due to the funding timeframe those recruited at the end of the recruitment period would not have time to complete this assessment. This 18 month assessment will just provide a slightly longer follow up period. |
| Intervention type | Behavioural |
| Primary outcome measure | Feasibility outcomes measured using patient records at the end of the study: 1. Recruitment rates 2. Compliance rates-intervention 3. Completion rates-data collection |
| Secondary outcome measures | 1. Periodontal scores. Periodontal assessment: Bleeding on Probing (BOP) (yes/no); periodontal pocket depths (mm)-four gingival sites/tooth; dental plaque- O’Leary plaque index (yes/no)-four surfaces/tooth at screening, 6 months, 12 months 2. Cognitive scores. Cognitive assessment: Clinical Dementia Rating Sum of Boxes (CDR-SB): an appropriate and widely used primary outcome measures for early and late dementia. Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-Cog11), and Bristol Activities of Daily Living Scale (BADLS), measuring functional ability at screening, 6 months, 12 months, 18 months 3. Blood levels of markers that are indicative of inflammation. Blood/saliva (laboratory research): Assessed for inflammatory response and bacterial load to confirm that bacteraemia and that pathogens have been reduced by the treatment at screening, 6 months, 12 months 4. Qualitative data (mini interview) regarding the perceived acceptability and success of the intervention at the end of the study |
| Overall study start date | 01/07/2022 |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 60 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 80; UK Sample Size: 80 (80 participants were planned to be screened in order to reach the recruitment target of 50 participants randomised onto the study) |
| Total final enrolment | 53 |
| Key inclusion criteria | 1. Diagnosis of either amnesic or multidomain mild cognitive Impairment with memory loss or early-stage Alzheimer's disease 2. Capacity to consent 3. Periodontitis (periodontal pockets of >4 mm with bleeding on probing) 4. Aged 60 years or over 5. A project partner to attend at least the first study appointment 6. A minimum of 6 teeth |
| Key exclusion criteria | 1. Lack of one or more of the inclusion criteria 2. Uncontrolled diabetes 3. Uncontrolled dental disease that is not periodontitis 4. Scores of >=3 on the American Society of Anaesthesiologists Physical-Status-Classification-System |
| Date of first enrolment | 09/01/2023 |
| Date of final enrolment | 01/08/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Bristol
BS1 2LX
United Kingdom
Cirencester
GL7 1QX
United Kingdom
Horfield
Bristol
BS7 8TR
United Kingdom
Gloucester
GL1 5JN
United Kingdom
Dursley
GL11 4AE
United Kingdom
Bristol
BS7 0NQ
United Kingdom
Portishead
Bristol
BS20 6JY
United Kingdom
Bristol
BS6 6SA
United Kingdom
Cheltenham
GL50 1HX
United Kingdom
Yate
Bristol
BS37 4AP
United Kingdom
Horfield
Bristol
BS7 0PD
United Kingdom
Stroud
GL5 2HN
United Kingdom
Cardiff
CF14 6HB
United Kingdom
Sponsor information
Hospital/treatment centre
Trust Headquarters
Marlborough Street
Bristol
BS1 3NU
England
United Kingdom
| Phone | +44 0117 34 20233 |
|---|---|
| researchapprovals@uhbw.nhs.uk |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The anonymised participant data (clinical scores and questionnaire data) generated during the current study will be shared once the data has been published and will be stored in the publicly available University of Bristol Research Data Repository/https://data.bris.ac.uk/data/ with a DOI maintained for a minimum of 20 years. Data will be made available as restricted access to bonafide researchers who provide a methodologically sound proposal and evidence of ethical approval (if required), subject to the agreement of the University of Bristol Data Access Committee for analysis to achieve aims in the approved proposal. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 3.0 | 15/12/2022 | 12/05/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
15/08/2024: Contact details updated. The target number of participants was updated to add "80 participants were planned to be screened in order to reach the recruitment target of 50 participants randomised onto the study".
13/08/2024: Total final enrolment added.
11/01/2024: The following changes have been made:
1. The recruitment end date was changed from 01/02/2024 to 01/08/2024.
2. The overall study end date was changed from 30/06/2025 to 31/12/2025.
3. The intention to publish date was changed from 30/06/2026 to 31/12/2026.
12/05/2023: Protocol and study website added.
04/01/2023: The recruitment start date was changed from 04/01/2023 to 09/01/2023.
19/12/2022: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/12/2022 to 04/01/2023.
20/10/2022: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
