Multicentre, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Effect of a 30-week Caffeine Treatment on Cognition in Alzheimer's Disease at Beginning to Moderate Stages

University Hospital, Lille19 sites in 1 country248 target enrollmentMarch 1, 2021

ConditionsAlzheimer Disease

InterventionsPlacebo Caffeine

DrugsCaffeine Placebo

Overview

Phase: Phase 3
Intervention: Placebo
Conditions: Alzheimer Disease
Sponsor: University Hospital, Lille
Enrollment: 248
Locations: 19
Primary Endpoint: Changes in NTB scores
Status: Recruiting
Last Updated: 12 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Sporadic Alzheimer's disease is a multifactorial illness arising a major medico-economic stakes for our aging societies. There is currently no curative treatment available.

Coffee is a complex beverage with psychostimulant properties whose main effective element, caffeine, has a pleiotropic effect on the central nervous system. Caffeine pharmacological properties enable its use like an Alzheimer's disease symptomatic treatment. Its supposed benefits mustn't obscure anxiety and insomnia caffeine effect at large dose, which Alzheimer's patients might be more vulnerable.

The main study objective is to evaluate placebo-controlled caffeine efficacy (30 treatments weeks) on cognitive decline in Alzheimer's disease dementia at beginning to moderate stage (MMSE 16-24).

Registry

clinicaltrials.gov

Start Date

March 1, 2021

End Date

December 1, 2027

Last Updated

12 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University Hospital, Lille

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 50 at screening
•Probable Alzheimer dementia according to the criteria of the National Institute on Aging-Alzheimer's Association; diagnosis must be supported by brain imaging (CT or MRI) and blood test (including ionogram, kidney and liver function, calcemia, CRP, TSH, B12 vitamins and folates) performed in routine care
•MMSE score ≥16
•Presence of an informant and caregiver, living with the patient
•IAChE and/or Memantine treatment non-compulsory ; If implemented it must be effective and stable for 2 months before the selection visit and must remain stable for the duration of the study

Exclusion Criteria

•Patients who refuse to adopt a low caffeine diet (eviction of tea, caffeinated sodas, chocolate in large quantities)
•Current major depressive episode according to DSM-5 criteria
•Another chronic pathology of the central nervous system
•Major anxiety according to the clinician (consistent with the corresponding nPI-R items that must indicate a severity \>2 and an impact \>3)
•Sleep disorders defined by severity and an impact on NPI-R; a patient fitted for OSA may be included if the device has been in use for 3 months and well tolerated (stable)
•Decompensated heart disease or severe rhythm disorder (excluding slow, treated and stable chronic atrial fibrillation)
•Active smoking
•For childbearing women : pregnancy in progress or planned (A pregnancy test will be performed)
•Patients who take forbidden treatment :
•Psychotropic treatments introduced or modified \< 2 months before inclusion

Arms & Interventions

placebo

after a 3 weeks up titration period, 2 capsules per day during 27 weeks

Intervention: Placebo

Caffeine

after a 3 weeks up titration period, 1 capsule of 200 mg twice a day during 27 weeks (ie 400mg/day)

Intervention: Caffeine

Outcomes

Primary Outcomes

Changes in NTB scores

Time Frame: 30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment

Secondary Outcomes

Caffeine treatment effect on TAP scores(30 weeks after randomization)
persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period(36 weeks after randomization)
Caffeine effect heterogeneity: impact of caffeine metabolism speed(30 weeks after randomization)
Caffeine treatment effect on Epworth score(30 weeks after randomization)
Caffeine treatment effect on QoL-AD score(30 weeks after randomization)
Caffeine treatment effect on DAD-6 score(30 weeks after randomization)
persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period(36 weeks after randomization)
persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period(36 weeks after randomization)
Caffeine treatment effect on MMSE score(30 weeks after randomization)
Caffeine treatment effect on CGIC score(30 weeks after randomization)
Caffeine treatment effect on Zarit score(30 weeks after randomization)
persistent effect of caffeine treatment on MMSE score after a 6 weeks wash out period(36 weeks after randomization)
persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period(36 weeks after randomization)
Caffeine effect heterogeneity: impact of gender(30 weeks after randomization)
Caffeine treatment effect on NTB subscores(30 weeks after randomization)
persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period(36 weeks after randomization)
Caffeine safety profile: NPI scores(30 weeks after randomization)
Caffeine safety profile: heart beat(30 weeks after randomization)
persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period(36 weeks after randomization)
Caffeine effect heterogeneity: impact of AD treatment(30 weeks after randomization)
Caffeine effect heterogeneity: impact of ApoE4 status(30 weeks after randomization)
Caffeine safety profile: blood pressure(30 weeks after randomization)
Caffeine and its derivatives concentrations in blood samples(30 weeks after randomization)