Cognitive DeclinePhase 2MET-FINGERNCT05109169
METformin and FINGER Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia
A Phase 2 study testing FINGER 2.0 multidomain lifestyle-based intervention and Self-guided multidomain lifestyle intervention in people with Cognitive Decline and Cognitive Impairment, run by Imperial College London at 3 sites in 3 countries.
Trial summary
Dementia is the main cause of disability in older adults, currently affecting about 50 million people world-wide with this number estimated to triple in the next 30 years. In MET-FINGER, we aim to understand whether the FINGER 2.0 multidomain intervention, combining healthy lifestyle changes and a drug for diabetes… Read more about this study
- Who is it for?
- Ages 60 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Decline, Cognitive Impairment, Dementia
- What is being tested?
- FINGER 2.0 multidomain lifestyle-based intervention and Self-guided multidomain lifestyle intervention
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 25 Jan 2023to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Main inclusion criteria (all participants)
- Age 60-79 years.
- Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Risk Score ≥6 points.
- Cognitive performance at the mean level or slightly lower than expected for age according to local population norms based on the Montreal Cognitive Assessment (MoCA) test and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal learning test.
- Proficiency in the local language (English, Finnish or Swedish)
- Inclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention arm)
- No diagnosed diabetes or known contraindications to metformin treatment.
- Elevated adiposity (BMI≥25 kg/m2 OR waist circumference > 102 cm in men and > 88 cm in women) OR mildly impaired fasting glucose (6.1-6.9 mmol/l).
Who cannot join
- Main exclusion criteria (all participants)
- Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician).
- Current or past use of medications for Alzheimer's Disease or related diseases (e.g., cholinesterase inhibitors, memantine, aducanumab).
- Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement.
- Other known significant neurologic disease (including e.g., Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumour, progressive, supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities).
- Any other condition affecting safe engagement in the intervention (e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within the previous year).
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- Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation.
- Coincident participation in the active phase of another intervention trial.
- A member of the household already enrolled in the MET-FINGER trial
- Exclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention group)
- Use of metformin for any indication.
- History of intolerance to metformin used for any indication.
- Diabetes diagnosed or suspected at baseline (e.g., HbA1c≥6.5%, fasting glucose ≥7 mmol/l, or 2HPG≥11.1 mmol/l).
- Metformin contraindications, e.g., history/presence of known renal or liver disease, congestive heart failure, alcohol abuse, calculated Glomerular Filtration Rate<60 ml/min.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Finland1 site
Finnish Institute of Health and Welfare - THL
Helsinki, FI-00271
United Kingdom1 site
Ageing Epidemiology Research Unit, Imperial College London
London, W6 8RP
About this study
Official title: Multimodal METformin and FINGER Lifestyle Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia: a Phase IIb Multi-national Randomised, Controlled Trial
Dementia is the main cause of disability in older adults, currently affecting about 50 million people world-wide with this number estimated to triple in the next 30 years. In MET-FINGER, we aim to understand whether the FINGER 2.0 multidomain intervention, combining healthy lifestyle changes and a drug for diabetes (metformin), may help reduce the risk of dementia and improve health and independence among older adults.
The study primary objective is to test the effect of the intervention, compared to healthy lifestyle advice, on the change in cognition, measured as a composite score including 14 of neuropsychological/cognitive tests. The secondary objective is to test the intervention effect on change in individual cognitive domains, functioning level, and risk factors for dementia (e.g., lifestyle, medical, and psychosocial). To this aim, a range of personal/health-related data and blood samples, will be collected. Potential interactions between metformin and lifestyle changes; potential disease-modifying effects; and feasibility of the metformin + lifestyle combination will be explored.
Read more
600 older people with risk factors for dementia, but without dementia/substantial cognitive impairment, will be recruited in the United Kingdom, Finland, and Sweden (at least 50% with higher genetic risk of Alzheimer's Disease/dementia based on the Apolipoprotein E (APOE) gene). Participants will be randomly assigned 1:1 to either a self-guided multidomain lifestyle intervention or to the FINGER 2.0 multidomain lifestyle-based intervention. Outcome assessors will be blinded to group allocation. Within the FINGER 2.0 intervention group, participants at increased risk of diabetes, will be randomly assigned 1:1:1 to either the metformin 2000mg/day, metformin 1000mg/day, or placebo group (double blinded). The intervention duration is 24 months.
The lifestyle intervention includes four main components: physical exercise, diet, brain training and health checks. In the self-guided group, participants will create their own program, based on health advice and recommendations which will be provided during the study. In the FINGER 2.0 intervention group, participants will receive intensive lifestyle guidance, and participate in structured activities, which will be as tailored as possible on each person's daily habits and needs.
Over the 2-year study period, all participants will attend four assessment visits: baseline, 6-, 12-, and 24-months.
Read the detailed description
After being identified and pre-screened in relevant registers, potential participants will undergo a screening assessment (after providing informed consent for the screening procedures) where inclusion criteria related to both cognition and cardiovascular/lifestyle risk factors will be checked. Participants meeting the inclusion criteria will undergo the exclusion criteria assessment with the study physician.
Eligible participants will be invited to the baseline visit where informed consent for the full study will be signed, baseline assessment will be conducted, and participants will be randomized to either the FINGER 2.0 multidomain lifestyle-based intervention or self-guided multidomain lifestyle intervention group. Based on the results of the baseline assessment, the eligibility to the metformin/placebo treatment will be assessed in all participants randomized to the FINGER 2.0 intervention group. Eligible participants will be further randomized to one of the three metformin treatment groups (metformin 2000mg/day, metformin 1000mg/day, or placebo). Non eligible participants will continue the study by following the structured lifestyle intervention alone.
In the self-guided intervention group, participants will build their own healthy lifestyle program based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the visits.
Within the FINGER 2.0 intervention group, participants will be invited to attend individual consultations and group meeting sessions in relation to the four intervention components (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring). As part of the physical activity component, group training sessions with a physiotherapist/professional trainer will be organized both at a gym as well as online. Within the cognitive training component, participants will have access to an online cognitive training program for independent training sessions. Individually tailored recommendations and plans will be provided to each participant.
Metformin and placebo will be dispensed every 3 months, both administered orally. The active drug is Glucophage® XR 500. All participants randomized to the metformin/placebo groups will receive 4 identical tablets per day as follows:
- 2000mg/day: 4x500mg metformin
- 1000mg/day: 2x500mg metformin + 2x500mg placebo
- Placebo: 4x500mg placebo.
Metformin will be titrated weekly from 500mg/day up to 2000mg/day over 4 weeks. Participants who do not tolerate the treatment will be allowed to remain in the study either in a lower dose treatment group, or receiving the structured lifestyle intervention only.
Participants will not be actively told to what lifestyle intervention group they have been assigned and assessors for primary and secondary outcomes will be blinded to the lifestyle group allocation. The metformin/placebo treatment will be conducted in double blind.
- Conditions
- Cognitive Decline, Cognitive Impairment, Dementia
- Being tested
- FINGER 2.0 multidomain lifestyle-based intervention, Self-guided multidomain lifestyle intervention
- Keywords
- Dementia prevention, FINGER multidomain lifestyle intervention, Metformin, World-Wide FINGERs, Drug repurposing
- Medical subject headings
- Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FINGER 2.0 multidomain lifestyle-based interventionCombination product
Multimodal lifestyle-based precision prevention intervention, including:
- Optimized FINGER multidomain lifestyle intervention (diet, physical activity, cognitive training and cardiovascular/metabolic risk monitoring and social interaction)
- Metformin (Glucophage® XR)
Self-guided multidomain lifestyle interventionOther
Participants build their own healthy lifestyle program based on standard healthy lifestyle advice on diet, physical activity, cognitive training and cardiovascular/metabolic risk
| Study group | Role | What they receive |
|---|---|---|
| Self-guided multidomain lifestyle intervention | Sham comparator | In this group, participants will build their own healthy lifestyle program based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the study visits, covering four main components (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring). The intervention duration is 2 years. Receives: Other: Self-guided multidomain lifestyle intervention |
| FINGER 2.0 multidomain lifestyle-based intervention | Active comparator | Within this group, participants will receive a structured intensive lifestyle intervention through individual consultations and group meeting sessions. Four main lifestyle components will be included (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring) as well as social interaction through the group meetings/sessions.
In this group, participants eligible for metformin treatment will be further randomised to either:
* 2000mg/day
* 1000mg/day
* placebo.
Metformin and placebo will be dispensed every 3 months, both administered orally. The intervention duration is 2 years Receives: Combination Product: FINGER 2.0 multidomain lifestyle-based intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cognition, unit on a scale.
Composite z-score of an extended Neuropsychological Test Battery (NTB) adapted from the FINGER trial and including:
- Wechsler Memory Scale Revised (WMS-III, WMS-R) logical memory, immediate
- WMS-R logical memory, delayed
- WMS-R visual paired associates, immediate
- WMS-R visual paired associates, delayed
- WMS-R Digit Span, total
- Hopkins Verbal Learning Test (HVLT), learning
- HVLT, recall
- CERAD category fluency
- Category fluency (fruits and vegetables)
- Trail Making Test (TMT) A
- TMT B, shifting score B-A
- Stroop Test, shortened 40-stimulus version, condition 2
- Stroop Test, condition 3, interference score 3 - 2
- Wechsler Adult Intelligence Scale (WAIS) Digit Symbol Substitution Test (DSST).
The z-score values range from -3 standard deviations to +3 standard deviations of the result distribution with higher score indicating better outcome.
Measured: Baseline, 12- and 24-months
Secondary outcomes (31)
Change in individual cognitive domains, unit on a scale.
Composite z-scores for the:
- memory
- executive function
- processing speed domains that are included in the NTB used as measure for the primary outcome. The z-score values range from -3 standard deviations to +3 standard deviations of the result distribution with higher score indicating better outcome.
Measured: Baseline, 12- and 24-months
Change in functioning level - Clinical Dementia Rating (CDR), unit on a scale
CDR Sum of Boxes (0-18), with lower score indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in functioning level - Katz index, unit on a scale
Activity of Daily Living, Katz Index. Self-reported questionnaire ranking the independence in six basic daily functions. For each activity, the participant is rated either dependent (0 points) or independent (1 point). The total score ranges 0-6 with a higher score indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in functioning level - Lawton-Brody scale, unit on a scale
Activity of Daily Living, Lawton-Brody Scale. Self-reported questionnaire assessing the level of functioning in eight daily activities necessary for living in the community. For each activity, the participant is rated either dependent (0 points) or independent (1 point). Score ranges 0-8, with a higher score indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in healthy lifestyle, unit on a scale.
Healthy Lifestyle Index, a composite score (range 0-24, with higher score indicating a better outcome) including self-reported data on diet, physical activity, smoking and alcohol, and cognitive/social activities.
Measured: Baseline, 12- and 24-months
Change in systolic blood pressure, mmHg.
Lower systolic blood pressure indicates a better outcome.
Measured: Baseline, 12- and 24-months
Change in diastolic blood pressure, mmHg.
Lower diastolic blood pressure indicates a better outcome.
Measured: Baseline, 12- and 24-months
Change in Body Mass Index (BMI), kg/m2.
Calculated using baseline height, with lower BMI value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in waist circumference, cm.
Lower value indicates a better outcome, with lower waist circumference value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in waist-hip ratio, unit on a scale.
Values ranging up to 1 with lower waist/hip ratio value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in blood lipids - Total Cholesterol, mmol/L.
Measured from serum with lower cholesterol value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in blood lipids - HDL Cholesterol, mmol/L.
Measured from serum with cholesterol higher value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in blood lipids - LDL Cholesterol, mmol/L.
Measured from serum with lower cholesterol value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change blood triglycerides, mmol/L.
Measured from serum with lower triglycerides value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in plasma glucose, mmol/L
Measured from fasting blood sample, with lower glucose value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in glycated haemoglobin (HbA1c), %
Measured from fasting blood sample, with lower HbA1c value indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), unit on a scale.
Calculated using fasting plasma glucose and fasting serum insulin, with lower values indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in 2-hour plasma glucose, mmol/L.
Measured with Oral Glucose Tolerance Test, only in participants included in the metformin/placebo treatment, and with lower glucose values indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in dietary intake, unit on a scale.
FINGER Diet Index, with values ranging 0-9, and higher score indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in physical activity - weekly frequency, unit on a scale.
Self-reported number of sessions moderate-to-vigorous intensity exercise per week. Higher number of sessions indicate a better outcome.
Measured: Baseline, 12- and 24-months
Change in physical activity - Minnesota questionnaire, unit on a scale.
Self-reported physical exercise in the previous two weeks, using a modified version of the Minnesota Leisure Time Physical Activity Questionnaire, as number of sessions and average duration for each of the activities listed in the questionnaire.
Higher levels of physical activity indicate a better outcome.
Measured: Baseline, 12- and 24-months
Change in physical activity - Actigraph, unit on a scale.
Objective measure of time spent carrying out physical activity using a hip accelerometer (ActiGraph model wGT3X-BT) that the participants will wear for 7 consecutive days.
Higher levels of physical activity indicate better outcome.
Measured: Baseline, 12- and 24-months
Change in physical functioning - Short Physical Performance Battery (SPPB), unit on a scale.
The SPPB is assessed in three domains: balance standing (score range: 0-4), chair standing (score range: 0-4), and gait speed (score range: 0-4). The total score (range: 0-12) is the sum of the three scores. Higher scores indicate a better outcome.
Measured: Baseline, 24-months
Change in physical functioning - Hand-grip strength, kg
Measured using a hand-grip dynamometer, with higher measures indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in physical functioning -Timed 10-metre dual task, seconds.
The test measure the time needed to walk 10 metres while carrying out a cognitive task (e.g. naming letters of the alphabet), with shorter times indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in depressive symptoms, unit on a scale.
Center for Epidemiological Studies Depression scale. Values ranging 0-60, with lower scores indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in stress-related symptoms, unit on a scale
Perceived Stress Scale. Values ranging 0-40, with lower scores indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in sleep problems, unit on a scale
Insomnia Severity Index. Values ranging 0-28, with lower scores indicating a better outcome.
Measured: 2 years
Change in health-related quality of life - "Research And Development-36" (RAND-36), unit on a scale
The scale values are ranging 0-100, with higher scores indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in health-related quality of life - "15D-questionnaire", unit on a scale
The scale values range 0-1, with higher scores indicating a better outcome.
Measured: Baseline, 12- and 24-months
Change in utilisation of health resources, unit on a scale
Number of e.g., hospitalization and doctors appointments, either self-reported and/or, if possible, from General Practitioners, and/or electronic health records of national healthcare registries. Lower use of healthcare resources indicates a better outcome.
Measured: Baseline, 12- and 24-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start25 Jan 2023
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are initially randomized 1:1 to two parallel arms: * self-guided multidomain lifestyle intervention * FINGER 2.0 multidomain lifestyle-based intervention Participants in the FINGER 2.0 intervention who are eligible for metformin treatment will be further randomized 1:1:1 to either: * metformin 2000mg/day * metformin 1000mg/day * placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Drug Discovery Foundation, Alzheimerfonden, Region Stockholm, Merck KGaA, Darmstadt, Germany, Finnish Institute for Health and Welfare, Fingers Brain Health Institute, Karolinska University Hospital, Karolinska Institutet, Alzheimer's Association
- Responsible party
- Sponsor
- Investigators
- Tiia Ngandu, MD, PhD, Principal investigator, Finnish Institute of Health and Welfare, FinlandFrancesca Mangialasche, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05109169
- Sponsor's protocol ID
- 21CX6667
- Other IDs
- 2021-005213-14, 2022-500438-27-01
- Acronym
- MET-FINGER
- Status last verified
- Jul 2026
- First submitted
- 26 Oct 2021
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The MET-FINGER Steering Committee and Management Group are open to requests from external researchers for data collected in this study. Applicants will be asked to submit a study protocol, including the research question, planned analysis, and data required. Committee will evaluate this plan (i.e., relevance of the research question, suitability of data, quality of proposed analyses, planned/ongoing MET-FINGER analyses, and other matters) on a case-by-case basis and provide the data or reject the request. Shared data will encompass the data dictionary and de-identified data only. Any analysis will be conducted in collaboration with the MET-FINGER Management Group. Access is subject to the MET-FINGER legal framework. An access agreement will be prepared and signed by both parties.
Publications
Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016 Jul 30;8(1):23. doi: 10.1186/s13195-016-0188-8.
PubMed 27473681Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.
PubMed 25771249Kivipelto M, Mangialasche F, Snyder HM, Allegri R, Andrieu S, Arai H, Baker L, Belleville S, Brodaty H, Brucki SM, Calandri I, Caramelli P, Chen C, Chertkow H, Chew E, Choi SH, Chowdhary N, Crivelli L, Torre R, Du Y, Dua T, Espeland M, Feldman HH, Hartmanis M, Hartmann T, Heffernan M, Henry CJ, Hong CH, Hakansson K, Iwatsubo T, Jeong JH, Jimenez-Maggiora G, Koo EH, Launer LJ, Lehtisalo J, Lopera F, Martinez-Lage P, Martins R, Middleton L, Molinuevo JL, Montero-Odasso M, Moon SY, Morales-Perez K, Nitrini R, Nygaard HB, Park YK, Peltonen M, Qiu C, Quiroz YT, Raman R, Rao N, Ravindranath V, Rosenberg A, Sakurai T, Salinas RM, Scheltens P, Sevlever G, Soininen H, Sosa AL, Suemoto CK, Tainta-Cuezva M, Velilla L, Wang Y, Whitmer R, Xu X, Bain LJ, Solomon A, Ngandu T, Carrillo MC. World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia. Alzheimers Dement. 2020 Jul;16(7):1078-1094. doi: 10.1002/alz.12123. Epub 2020 Jul 5.
PubMed 32627328Barbera M, Lehtisalo J, Perera D, Aspo M, Cross M, De Jager Loots CA, Falaschetti E, Friel N, Luchsinger JA, Gavelin HM, Peltonen M, Price G, Neely AS, Thunborg C, Tuomilehto J, Mangialasche F, Middleton L, Ngandu T, Solomon A, Kivipelto M; MET-FINGER study team. A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol. Alzheimers Res Ther. 2024 Jan 31;16(1):23. doi: 10.1186/s13195-023-01355-x.
PubMed 38297399
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal METformin and FINGER Lifestyle Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia: a Phase IIb Multi-national Randomised, Controlled Trial
- ClinicalTrials.gov ID
- NCT05109169
- Acronym / sponsor ID
- MET-FINGER / 21CX6667
- Conditions
- Cognitive Decline, Cognitive Impairment, Dementia
- Keywords
- Dementia prevention, FINGER multidomain lifestyle intervention, Metformin, World-Wide FINGERs, Drug repurposing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Alzheimer's Drug Discovery Foundation, Alzheimerfonden, Region Stockholm, Merck KGaA, Darmstadt, Germany, Finnish Institute for Health and Welfare, Fingers Brain Health Institute, Karolinska University Hospital, Karolinska Institutet, Alzheimer's Association
- Study start
- 25 Jan 2023 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 5 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dementia is the main cause of disability in older adults, currently affecting about 50 million people world-wide with this number estimated to triple in the next 30 years. In MET-FINGER, we aim to understand whether the FINGER 2.0 multidomain intervention, combining healthy lifestyle changes and a drug for diabetes (metformin), may help reduce the risk of dementia and improve health and independence among older adults.
The study primary objective is to test the effect of the intervention, compared to healthy lifestyle advice, on the change in cognition, measured as a composite score including 14 of neuropsychological/cognitive tests. The secondary objective is to test the intervention effect on change in individual cognitive domains, functioning level, and risk factors for dementia (e.g., lifestyle, medical, and psychosocial). To this aim, a range of personal/health-related data and blood samples, will be collected. Potential interactions between metformin and lifestyle changes; potential disease-modifying effects; and feasibility of the metformin + lifestyle combination will be explored.
600 older people with risk factors for dementia, but without dementia/substantial cognitive impairment, will be recruited in the United Kingdom, Finland, and Sweden (at least 50% with higher genetic risk of Alzheimer's Disease/dementia based on the Apolipoprotein E (APOE) gene). Participants will be randomly assigned 1:1 to either a self-guided multidomain lifestyle intervention or to the FINGER 2.0 multidomain lifestyle-based intervention. Outcome assessors will be blinded to group allocation. Within the FINGER 2.0 intervention group, participants at increased risk of diabetes, will be randomly assigned 1:1:1 to either the metformin 2000mg/day, metformin 1000mg/day, or placebo group (double blinded). The intervention duration is 24 months.
The lifestyle intervention includes four main components: physical exercise, diet, brain training and health checks. In the self-guided group, participants will create their own program, based on health advice and recommendations which will be provided during the study. In the FINGER 2.0 intervention group, participants will receive intensive lifestyle guidance, and participate in structured activities, which will be as tailored as possible on each person's daily habits and needs.
Over the 2-year study period, all participants will attend four assessment visits: baseline, 6-, 12-, and 24-months.
Detailed description
After being identified and pre-screened in relevant registers, potential participants will undergo a screening assessment (after providing informed consent for the screening procedures) where inclusion criteria related to both cognition and cardiovascular/lifestyle risk factors will be checked. Participants meeting the inclusion criteria will undergo the exclusion criteria assessment with the study physician.
Eligible participants will be invited to the baseline visit where informed consent for the full study will be signed, baseline assessment will be conducted, and participants will be randomized to either the FINGER 2.0 multidomain lifestyle-based intervention or self-guided multidomain lifestyle intervention group. Based on the results of the baseline assessment, the eligibility to the metformin/placebo treatment will be assessed in all participants randomized to the FINGER 2.0 intervention group. Eligible participants will be further randomized to one of the three metformin treatment groups (metformin 2000mg/day, metformin 1000mg/day, or placebo). Non eligible participants will continue the study by following the structured lifestyle intervention alone.
In the self-guided intervention group, participants will build their own healthy lifestyle program based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the visits.
Within the FINGER 2.0 intervention group, participants will be invited to attend individual consultations and group meeting sessions in relation to the four intervention components (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring). As part of the physical activity component, group training sessions with a physiotherapist/professional trainer will be organized both at a gym as well as online. Within the cognitive training component, participants will have access to an online cognitive training program for independent training sessions. Individually tailored recommendations and plans will be provided to each participant.
Metformin and placebo will be dispensed every 3 months, both administered orally. The active drug is Glucophage® XR 500. All participants randomized to the metformin/placebo groups will receive 4 identical tablets per day as follows:
- 2000mg/day: 4x500mg metformin
- 1000mg/day: 2x500mg metformin + 2x500mg placebo
- Placebo: 4x500mg placebo.
Metformin will be titrated weekly from 500mg/day up to 2000mg/day over 4 weeks. Participants who do not tolerate the treatment will be allowed to remain in the study either in a lower dose treatment group, or receiving the structured lifestyle intervention only.
Participants will not be actively told to what lifestyle intervention group they have been assigned and assessors for primary and secondary outcomes will be blinded to the lifestyle group allocation. The metformin/placebo treatment will be conducted in double blind.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are initially randomized 1:1 to two parallel arms: * self-guided multidomain lifestyle intervention * FINGER 2.0 multidomain lifestyle-based intervention Participants in the FINGER 2.0 intervention who are eligible for metformin treatment will be further randomized 1:1:1 to either: * metformin 2000mg/day * metformin 1000mg/day * placebo
| Arm | Type | Receives |
|---|---|---|
| Self-guided multidomain lifestyle intervention | Sham comparator | Other: Self-guided multidomain lifestyle interventionIn this group, participants will build their own healthy lifestyle program based on standard healthy lifestyle advice that they will receive at individual consultations with the study physician/nurse as part of the study visits, covering four main components (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring). The intervention duration is 2 years. |
| FINGER 2.0 multidomain lifestyle-based intervention | Active comparator | Combination Product: FINGER 2.0 multidomain lifestyle-based interventionWithin this group, participants will receive a structured intensive lifestyle intervention through individual consultations and group meeting sessions. Four main lifestyle components will be included (diet, physical activity, cognitive training, and cardiovascular/metabolic risk monitoring) as well as social interaction through the group meetings/sessions. In this group, participants eligible for metformin treatment will be further randomised to either: * 2000mg/day * 1000mg/day * placebo. Metformin and placebo will be dispensed every 3 months, both administered orally. The intervention duration is 2 years |
Who may qualify
- Ages
- 60 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Main inclusion criteria (all participants)
- Inclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention arm)
Key exclusion criteria (14 listed)
- Main exclusion criteria (all participants)
- Exclusion criteria for metformin/placebo treatment (only for participants in the FINGER 2.0 multimodal lifestyle-based intervention group)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FINGER 2.0 multidomain lifestyle-based interventionMultimodal lifestyle-based precision prevention intervention, including: * Optimized FINGER multidomain lifestyle intervention (diet, physical activity, cognitive training and cardiovascular/metabolic risk monitoring and social interaction) * Metformin (Glucophage® XR) | Combination product | FINGER 2.0 multidomain lifestyle-based intervention |
| Self-guided multidomain lifestyle interventionParticipants build their own healthy lifestyle program based on standard healthy lifestyle advice on diet, physical activity, cognitive training and cardiovascular/metabolic risk | Other | Self-guided multidomain lifestyle intervention |
Primary outcome
Change in cognition, unit on a scale.
Time frame: Baseline, 12- and 24-months
Composite z-score of an extended Neuropsychological Test Battery (NTB) adapted from the FINGER trial and including: 1. Wechsler Memory Scale Revised (WMS-III, WMS-R) logical memory, immediate 2. WMS-R logical memory, delayed 3. WMS-R visual paired associates, immediate 4. WMS-R visual paired associates, delayed 5. WMS-R Digit Span, total 6. Hopkins Verbal Learning Test (HVLT), learning 7. HVLT, recall 8. CERAD category fluency 9. Category fluency (fruits and vegetables) 10. Trail Making Test (TMT) A 11. TMT B, shifting score B-A 12. Stroop Test, shortened 40-stimulus version, condition 2 13. Stroop Test, condition 3, interference score 3 - 2 14. Wechsler Adult Intelligence Scale (WAIS) Digit Symbol Substitution Test (DSST). The z-score values range from -3 standard deviations to +3 standard deviations of the result distribution with higher score indicating better outcome.
31 secondary outcomes
Change in individual cognitive domains, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in functioning level - Clinical Dementia Rating (CDR), unit on a scale
Time frame: Baseline, 12- and 24-months
Change in functioning level - Katz index, unit on a scale
Time frame: Baseline, 12- and 24-months
Change in functioning level - Lawton-Brody scale, unit on a scale
Time frame: Baseline, 12- and 24-months
Change in healthy lifestyle, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in systolic blood pressure, mmHg.
Time frame: Baseline, 12- and 24-months
Change in diastolic blood pressure, mmHg.
Time frame: Baseline, 12- and 24-months
Change in Body Mass Index (BMI), kg/m2.
Time frame: Baseline, 12- and 24-months
Change in waist circumference, cm.
Time frame: Baseline, 12- and 24-months
Change in waist-hip ratio, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in blood lipids - Total Cholesterol, mmol/L.
Time frame: Baseline, 12- and 24-months
Change in blood lipids - HDL Cholesterol, mmol/L.
Time frame: Baseline, 12- and 24-months
Change in blood lipids - LDL Cholesterol, mmol/L.
Time frame: Baseline, 12- and 24-months
Change blood triglycerides, mmol/L.
Time frame: Baseline, 12- and 24-months
Change in plasma glucose, mmol/L
Time frame: Baseline, 12- and 24-months
Change in glycated haemoglobin (HbA1c), %
Time frame: Baseline, 12- and 24-months
Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in 2-hour plasma glucose, mmol/L.
Time frame: Baseline, 12- and 24-months
Change in dietary intake, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in physical activity - weekly frequency, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in physical activity - Minnesota questionnaire, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in physical activity - Actigraph, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in physical functioning - Short Physical Performance Battery (SPPB), unit on a scale.
Time frame: Baseline, 24-months
Change in physical functioning - Hand-grip strength, kg
Time frame: Baseline, 12- and 24-months
Change in physical functioning -Timed 10-metre dual task, seconds.
Time frame: Baseline, 12- and 24-months
Change in depressive symptoms, unit on a scale.
Time frame: Baseline, 12- and 24-months
Change in stress-related symptoms, unit on a scale
Time frame: Baseline, 12- and 24-months
Change in sleep problems, unit on a scale
Time frame: 2 years
Change in health-related quality of life - "Research And Development-36" (RAND-36), unit on a scale
Time frame: Baseline, 12- and 24-months
Change in health-related quality of life - "15D-questionnaire", unit on a scale
Time frame: Baseline, 12- and 24-months
Change in utilisation of health resources, unit on a scale
Time frame: Baseline, 12- and 24-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Background: PubMed 27473681Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016 Jul 30;8(1):23. doi: 10.1186/s13195-016-0188-8.
- Background: PubMed 25771249Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.
- Background: PubMed 32627328Kivipelto M, Mangialasche F, Snyder HM, Allegri R, Andrieu S, Arai H, Baker L, Belleville S, Brodaty H, Brucki SM, Calandri I, Caramelli P, Chen C, Chertkow H, Chew E, Choi SH, Chowdhary N, Crivelli L, Torre R, Du Y, Dua T, Espeland M, Feldman HH, Hartmanis M, Hartmann T, Heffernan M, Henry CJ, Hong CH, Hakansson K, Iwatsubo T, Jeong JH, Jimenez-Maggiora G, Koo EH, Launer LJ, Lehtisalo J, Lopera F, Martinez-Lage P, Martins R, Middleton L, Molinuevo JL, Montero-Odasso M, Moon SY, Morales-Perez K, Nitrini R, Nygaard HB, Park YK, Peltonen M, Qiu C, Quiroz YT, Raman R, Rao N, Ravindranath V, Rosenberg A, Sakurai T, Salinas RM, Scheltens P, Sevlever G, Soininen H, Sosa AL, Suemoto CK, Tainta-Cuezva M, Velilla L, Wang Y, Whitmer R, Xu X, Bain LJ, Solomon A, Ngandu T, Carrillo MC. World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia. Alzheimers Dement. 2020 Jul;16(7):1078-1094. doi: 10.1002/alz.12123. Epub 2020 Jul 5.
- Derived from this study: PubMed 38297399Barbera M, Lehtisalo J, Perera D, Aspo M, Cross M, De Jager Loots CA, Falaschetti E, Friel N, Luchsinger JA, Gavelin HM, Peltonen M, Price G, Neely AS, Thunborg C, Tuomilehto J, Mangialasche F, Middleton L, Ngandu T, Solomon A, Kivipelto M; MET-FINGER study team. A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol. Alzheimers Res Ther. 2024 Jan 31;16(1):23. doi: 10.1186/s13195-023-01355-x.
- Individual participant dataSharing planned: Yes. The MET-FINGER Steering Committee and Management Group are open to requests from external researchers for data collected in this study. Applicants will be asked to submit a study protocol, including the research question, planned analysis, and data required. Committee will evaluate this plan (i.e., relevance of the research question, suitability of data, quality of proposed analyses, planned/ongoing MET-FINGER analyses, and other matters) on a case-by-case basis and provide the data or reject the request. Shared data will encompass the data dictionary and de-identified data only. Any analysis will be conducted in collaboration with the MET-FINGER Management Group. Access is subject to the MET-FINGER legal framework. An access agreement will be prepared and signed by both parties.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tiia Ngandu, MD, PhD principal investigator
Finnish Institute of Health and Welfare, Finland
Francesca Mangialasche, MD, PhD principal investigator
Karolinska Institutet
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FINGER 2.0 multidomain lifestyle-based intervention and Self-guided multidomain lifestyle intervention in people with Cognitive Decline and Cognitive Impairment, run by Imperial College London at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Finland, Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cognition, unit on a scale. (time frame: Baseline, 12- and 24-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05109169, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.