METformin and FINGER Intervention to Prevent Cognitive Impairment and Disability in Older Adults at Risk for Dementia

NCT ID: NCT05109169

Last Updated: 2024-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-25

Study Completion Date

2027-06-28

Brief Summary

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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

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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

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Cognitive Decline Cognitive Impairment Dementia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Lifestyle intervention: participants will not be told to what intervention group they have been assigned and outcome assessors will be blinded to the lifestyle intervention group allocation.

Metformin/placebo treatment within the FINGER 2.0 intervention group: double blind.

Study Groups

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Self-guided multidomain lifestyle intervention

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.

Group Type SHAM_COMPARATOR

Self-guided multidomain lifestyle intervention

Intervention Type OTHER

Participants build their own healthy lifestyle program based on standard healthy lifestyle advice on diet, physical activity, cognitive training and cardiovascular/metabolic risk

FINGER 2.0 multidomain lifestyle-based intervention

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

Group Type ACTIVE_COMPARATOR

FINGER 2.0 multidomain lifestyle-based intervention

Intervention Type COMBINATION_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)

Interventions

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FINGER 2.0 multidomain lifestyle-based intervention

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)

Intervention Type COMBINATION_PRODUCT

Self-guided multidomain lifestyle intervention

Participants build their own healthy lifestyle program based on standard healthy lifestyle advice on diet, physical activity, cognitive training and cardiovascular/metabolic risk

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Age 60-79 years.
2. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Risk Score ≥6 points.
3. 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.
4. Proficiency in the local language (English, Finnish or Swedish)

1. No diagnosed diabetes or known contraindications to metformin treatment.
2. 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).

Exclusion Criteria

1. Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician).
2. Current or past use of medications for Alzheimer's Disease or related diseases (e.g., cholinesterase inhibitors, memantine, aducanumab).
3. Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement.
4. 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).
5. Any other condition affecting safe engagement in the intervention (e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within the previous year).
6. Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation.
7. Coincident participation in the active phase of another intervention trial.
8. A member of the household already enrolled in the MET-FINGER trial

1. Use of metformin for any indication.
2. History of intolerance to metformin used for any indication.
3. Diabetes diagnosed or suspected at baseline (e.g., HbA1c≥6.5%, fasting glucose ≥7 mmol/l, or 2HPG≥11.1 mmol/l).
4. Metformin contraindications, e.g., history/presence of known renal or liver disease, congestive heart failure, alcohol abuse, calculated Glomerular Filtration Rate\<60 ml/min.
Minimum Eligible Age

60 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Alzheimer's Association

OTHER

Sponsor Role collaborator

Alzheimer's Drug Discovery Foundation

OTHER

Sponsor Role collaborator

Alzheimerfonden

UNKNOWN

Sponsor Role collaborator

Region Stockholm

OTHER_GOV

Sponsor Role collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

Finnish Institute for Health and Welfare

OTHER_GOV

Sponsor Role collaborator

Fingers Brain Health Institute

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tiia Ngandu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Finnish Institute of Health and Welfare, Finland

Francesca Mangialasche, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Finnish Institute of Health and Welfare - THL

Helsinki, , Finland

Site Status RECRUITING

Karolinska Institutet

Solna, , Sweden

Site Status RECRUITING

Ageing Epidemiology Research Unit, Imperial College London

London, , United Kingdom

Site Status RECRUITING

Countries

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Finland Sweden United Kingdom

Central Contacts

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Miia Kivipelto, MD, PhD

Role: CONTACT

+46(0)739940922

Alina Solomon, MD, PhD

Role: CONTACT

+358(0)403552015

Facility Contacts

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Tiia Ngandu

Role: primary

+358(0)405241759

Francesca Mangialasche

Role: primary

+46(0)703019466

Miia Kivipelto

Role: primary

+46739940922

Naia Headland-Vanni

Role: backup

+442033117290

References

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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.

Reference Type BACKGROUND
PMID: 27473681 (View on PubMed)

Ngandu 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.

Reference Type BACKGROUND
PMID: 25771249 (View on PubMed)

Kivipelto 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.

Reference Type BACKGROUND
PMID: 32627328 (View on PubMed)

Barbera 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.

Reference Type DERIVED
PMID: 38297399 (View on PubMed)

Other Identifiers

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2021-005213-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2022-500438-27-01

Identifier Type: OTHER

Identifier Source: secondary_id

21CX6667

Identifier Type: -

Identifier Source: org_study_id

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