A clinical trial to test a combination of lifestyle-based intervention with metformin in preventing dementia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Imperial College London

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Jun 2023 → ongoing

Decision date (initial)

2022-07-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Alzheimer’s Drug Discovery Foundation (ADDF) · Region Stockholm (ALF grant) · Alzheimer’s Association - Part the Cloud Gates Partnership 2020 (PTC) · Alzheimerfonden (AF)

External identifiers

EU CT number

2022-500438-27-01

ClinicalTrials.gov

NCT05109169

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy, Dose response

To test the effect of the 24-month FINGER 2.0 multimodal lifestyle-based intervention (structured multimodal intervention, active arm) versus a self-guided multimodal intervention (control / comparator arm) on change in cognition in an APOE ε4-enriched older population with increased dementia risk

Secondary objectives 13

1. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in cognitive domains (memory, executive function, processing speed),
2. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in functioning level
3. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in healthy lifestyle
4. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in cardiovascular and metabolic risk factors and markers
5. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on cardiovascular morbidity and mortality
6. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in dietary intake
7. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in physical activity
8. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in physical functioning
9. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in depressive symptoms,
10. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in stress-related symptoms
11. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in sleep problems
12. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in health-related quality of life,
13. To test the effect o f the 24-month FINGER 2.0 multimodal lifestyle-based intervention versus the self-guided multimodal intervention on change in utilisation of health resources

Conditions and MedDRA coding

Older adults with risk factors for dementia but dementia free and without substantial cognitive impairment. The intervention is aimed at preventing cognitive decline/dementia.

Study design 2 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

No trial data can be published without previous approval of the Trial Management Group (TMG). Data arisen from and samples collected during the trial (including Individual Participants Data) will not be made publicly available but will be available for collaborative sharing, after the main results of the trial have been published, and upon submission of an application to the TMG of the related research project for which the data/samples are requested. The TMG will assess and review the application and data/samples will be released upon approval.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. For all: Age 60-79 years
2. For all: CAIDE Dementia Risk Score ≥6 points
3. For all: Cognitive performance at the mean level or slightly lower than expected for age according to local population norms based on the MoCA test and the CERAD verbal learning test.
4. For all: Proficiency in the local language (English, Finnish or Swedish)
5. For metformin/placebo group: No diagnosed diabetes or known contraindications to metformin treatment.
6. For metformin/placebo group: 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 17

1. For all: Dementia or substantial cognitive impairment (e.g., memory clinic referral needed as judged by the study physician).
2. For all: Current or past use of medications for AD or related diseases (e.g., cholinesterase inhibitors, memantine, aducanumab).
3. For all: Diminished decision-making capacity, not capable of consenting or completing study assessments, based on clinical judgement.
4. For all: 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. For all: Any other condition affecting safe engagement in the intervention (e.g., malignant disease, major depression, symptomatic cardiovascular disease, revascularisation within the previous year)
6. For all: Severe loss of vision, hearing, or communicative ability; conditions preventing cooperation
7. For all: Coincident participation in the active phase of another intervention trial.
8. For all: A member of the household already enrolled in the MET-FINGER trial
9. For metformin/placebo group: Use of metformin for any indication.
10. For metformin/placebo group: History of intolerance to metformin used for any indication.
11. For metformin/placebo group: Diabetes diagnosed or suspected at baseline (e.g., HbA1c≥6.5%, fasting glucose ≥7 mmol/l, or 2HPG≥11.1 mmol/l).
12. For metformin/placebo group: Hypersensitivity to metformin or to any of the excipients or placebo compounds.
13. For metformin/placebo group: Metformin contraindications, e.g., history/presence of known renal or liver disease, congestive heart failure, alcohol abuse, calculated GFR<60 ml/min.
14. For metformin/placebo group: Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
15. For metformin/placebo group: Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock.
16. For metformin/placebo group: Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
17. For metformin/placebo group: Women of childbearing potential (WOCBP)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite z- score of an extended Neuropsychological Test Battery (NTB) adapted from the FINGER trial

Secondary endpoints 13

1. Composite z-scores for NTB memory, executive function, and processing speed domains (based on FINGER)
2. Clinical Dementia Rating Sum of Boxes, Instrumental Activities of Daily Living
3. Healthy Lifestyle Index, a composite score based on exercise, diet, lifestyle cardiovascular risk factors, and social and cognitive activity
4. BMI, waist, waist/hip ratio, blood pressure, lipid profile and glucose metabolism
5. Incident cardiovascular disease (e.g., myocardial infarction, angina pectoris, transient ischaemic attack, stroke, peripheral artery disease)
6. FINGER healthy diet index, nutrients and food intake
7. Self-reported and objectively measured levels of physical activity
8. Short Physical Performance Battery, hand grip strength, and timed 10-meter dual-task test
9. Center for Epidemiological Studies-Depression Scale
10. Perceived Stress Scale
11. Insomnia Severity Index
12. RAND36 and 15D scales for health-related quality of life
13. Self-reported and register data for utilisation of healthcare resources

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Imperial College London

Sponsor organisation

Imperial College London

Address

Praed Street

City

London

Postcode

W2 1NY

Country

United Kingdom

Scientific contact point

Organisation

Imperial College London

Contact name

MET-FINGER information desk

Public contact point

Organisation

Imperial College London

Contact name

MET-FINGER information desk

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications