NCT05109169

Brief 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 (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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for phase_2

Timeline
14mo left

Started Jan 2023

Typical duration for phase_2

Geographic Reach
3 countries

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress74%
Jan 2023Jun 2027

First Submitted

Initial submission to the registry

October 26, 2021

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 5, 2021

Completed
1.2 years until next milestone

Study Start

First participant enrolled

January 25, 2023

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2027

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 28, 2027

Last Updated

February 6, 2024

Status Verified

February 1, 2024

Enrollment Period

4.1 years

First QC Date

October 26, 2021

Last Update Submit

February 5, 2024

Conditions

Cognitive DeclineCognitive ImpairmentDementia

Keywords

Dementia preventionFINGER multidomain lifestyle interventionMetforminWorld-Wide FINGERsDrug repurposing

Outcome Measures

Primary Outcomes (1)

  • Change in cognition, unit on a scale.

    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.

    Baseline, 12- and 24-months

Secondary Outcomes (31)

  • Change in individual cognitive domains, unit on a scale.

    Baseline, 12- and 24-months

  • Change in functioning level - Clinical Dementia Rating (CDR), unit on a scale

    Baseline, 12- and 24-months

  • Change in functioning level - Katz index, unit on a scale

    Baseline, 12- and 24-months

  • Change in functioning level - Lawton-Brody scale, unit on a scale

    Baseline, 12- and 24-months

  • Change in healthy lifestyle, unit on a scale.

    Baseline, 12- and 24-months

  • +26 more secondary outcomes

Other Outcomes (8)

  • Exploratory - potential interactions between metformin and lifestyle changes

    Baseline, 12- and 24-months

  • Exploratory - potential disease-modifying effects - Amyloid β42/40 ratio, unit on a scale

    Baseline and 24-months

  • Exploratory - potential disease-modifying effects - Neurofilament light chain protein, pg/ml

    Baseline and 24-months

  • +5 more other outcomes

Study Arms (2)

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.

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

Combination Product: FINGER 2.0 multidomain lifestyle-based intervention

Interventions

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)

FINGER 2.0 multidomain lifestyle-based intervention
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

Self-guided multidomain lifestyle intervention

Eligibility Criteria

Age60 Years - 79 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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).

You may not qualify if:

  • 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).
  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Finnish Institute of Health and Welfare - THL

Helsinki, FI-00271, Finland

RECRUITING

Karolinska Institutet

Solna, 171 64, Sweden

RECRUITING

Ageing Epidemiology Research Unit, Imperial College London

London, W6 8RP, United Kingdom

RECRUITING

Related Publications (4)

  • 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.

    PMID: 27473681BACKGROUND

  • 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.

    PMID: 25771249BACKGROUND

  • 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.

    PMID: 32627328BACKGROUND

  • 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.

    PMID: 38297399DERIVED

MeSH Terms

Conditions

Cognitive DysfunctionDementia

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Tiia Ngandu, MD, PhD

    Finnish Institute of Health and Welfare, Finland

    PRINCIPAL INVESTIGATOR

  • Francesca Mangialasche, MD, PhD

    Karolinska Institutet

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Miia Kivipelto, MD, PhD

CONTACT

+46(0)739940922miia.kivipelto@ki.se

Alina Solomon, MD, PhD

CONTACT

+358(0)403552015alina.solomon@uef.fi

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: 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
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 26, 2021

First Posted

November 5, 2021

Study Start

January 25, 2023

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

June 28, 2027

Last Updated

February 6, 2024

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will share

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.

Time Frame
The trial Steering Committee and Management Group will consider applications for data after the trials results have been published and data will be made available according to the terms of the access agreement.
Access Criteria
As described above in the Plan Description.

Locations

SE(1)FI(1)GB(1)