Effect of CAFfeine on Cognition in Alzheimer's Disease (CAFCA)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Caffeine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 248
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thibaud LEBOUVIER, MD,PhD; Phone Number: +33 03 20 44 60 21; Email: thibaud.lebouvier@chru-lille.fr

Study Locations

• France
  • Amiens, France
    • Not yet recruiting
    • CHU Amiens
    • Contact: Olivier GODEFROY, MD
  • Arras, France
    • Not yet recruiting
    • CH ARRAS
    • Contact: Patrick LE COZ, MD
  • Beauvais, France
    • Not yet recruiting
    • CH Beauvais
    • Contact: Xavier CNOCKAERT, MD
  • Béthune, France
    • Not yet recruiting
    • CH Bethune
    • Contact: Isabelle LAVENU, MD
  • Caen, France
    • Not yet recruiting
    • CHU Caen
    • Contact: Olivier MARTINAUD, MD
  • Calais, France
    • Not yet recruiting
    • CH Calais
    • Contact: Olivier DEREEPER, MD
  • Dunkirk, France
    • Not yet recruiting
    • Ch Dunkerque
    • Contact: Abdelghani EL AZOUZI, MD
  • Le Quesnoy, France
    • Not yet recruiting
    • CH Le Quesnoy
    • Contact: Denis LEFEBVRE, MD
  • Lens, France
    • Not yet recruiting
    • CH LENS
    • Contact: Olivier SENECHAL, MD
  • Lille, France, 59037
    • Recruiting
    • Hopital Roger Salengro
    • Principal Investigator: Thibaut Lebouvier, MD
  • Lille, France
    • Not yet recruiting
    • CHU Lille consultation mémoire Les Bâteliers
    • Contact: Dominique HUVENT, MD
  • Roubaix, France
    • Not yet recruiting
    • CH Roubaix
    • Contact: Pierre FORZY, MD
  • Rouen, France
    • Not yet recruiting
    • CHU Rouen
    • Contact: David WALLON, MD
  • Saint-Quentin, France
    • Not yet recruiting
    • CH Saint Quentin
    • Contact: Jadwiga ATTIER-ZMUDKA, MD
  • Seclin, France
    • Not yet recruiting
    • CH Seclin
    • Contact: Véronique BERRIOT, MD
  • Tourcoing, France
    • Not yet recruiting
    • Ch Tourcoing
    • Contact: Karim GALLOUJ, MD
  • Valenciennes, France
    • Not yet recruiting
    • Ch Valenciennes
    • Contact: Anne DESPREZ, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
  • Chronic use of CYP1A2 inducing or inhibiting drugs
  • All caffeine-containing specialties
  • Drugs that influence caffeine metabolism
  • Drugs that may interact with caffeine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caffeine; after a 3 weeks up titration period, 1 capsule of 200 mg twice a day during 27 weeks (ie 400mg/day)	Drug: Caffeine; 100mg caffeine capsule treatment, beginning after caffeine diet during 6 weeks, titrate in 3 weeks (by 100mg stages) until 400mg aim dose per day in 2 doses during 27 weeks, and finally interrupt according to the same negative titration.
Placebo Comparator: placebo; after a 3 weeks up titration period, 2 capsules per day during 27 weeks	Drug: Placebo; Placebo capsule treatment, beginning after caffeine diet during 6 weeks, titrate in 3 weeks until 2 doses aim dose per day during 27 weeks, and finally interrupt according to the same negative titration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in NTB scores	difference between randomized value and value after 30 weeks of treatment	30 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Caffeine treatment effect on MMSE score	difference between randomized value and value after 30 weeks of treatment on MMSE score	30 weeks after randomization
Caffeine treatment effect on NTB subscores	difference between randomized value and value after 30 weeks of treatment on NTB subscores	30 weeks after randomization
Caffeine treatment effect on TAP scores	difference between randomized value and value after 30 weeks of treatment on TAP scores	30 weeks after randomization
Caffeine treatment effect on Epworth score	difference between randomized value and value after 30 weeks of treatment on Epworth score	30 weeks after randomization
Caffeine treatment effect on DAD-6 score	difference between randomized value and value after 30 weeks of treatment on DAD-6 score	30 weeks after randomization
Caffeine treatment effect on QoL-AD score	difference between randomized value and value after 30 weeks of treatment on QoL-AD score	30 weeks after randomization
Caffeine treatment effect on CGIC score	difference between randomized value and value after 30 weeks of treatment on CGIC score	30 weeks after randomization
Caffeine treatment effect on Zarit score	difference between randomized value and value after 30 weeks of treatment on Zarit score	30 weeks after randomization
persistent effect of caffeine treatment on MMSE score after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on MMSE score	36 weeks after randomization
persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on NTB subscores	36 weeks after randomization
persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on TAP scores	36 weeks after randomization
persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on Epworth score	36 weeks after randomization
persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on DAD-6 score	36 weeks after randomization
persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on QoL-AD score	36 weeks after randomization
persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period	difference between value after 30 weeks of treatment and value after a 6 weeks wash out period (from Week 30 to Week 36) on Zarit score	36 weeks after randomization
Caffeine effect heterogeneity: impact of AD treatment	impact of AD treatment on caffeine effect	30 weeks after randomization
Caffeine effect heterogeneity: impact of ApoE4 status	impact of ApoE4 status on caffeine effect	30 weeks after randomization
Caffeine effect heterogeneity: impact of caffeine metabolism speed	impact of caffeine metabolism on caffeine effect	30 weeks after randomization
Caffeine effect heterogeneity: impact of gender	impact of gender on caffeine effect	30 weeks after randomization
Caffeine safety profile: NPI scores	changes in NPI scores and subscores between caffeine and placebo arms	30 weeks after randomization
Caffeine safety profile: heart beat	changes in heart beat between caffeine and placebo arms	30 weeks after randomization
Caffeine safety profile: blood pressure	changes in blood pressure between caffeine and placebo arms	30 weeks after randomization
Caffeine and its derivatives concentrations in blood samples	increase in caffeinemia and its derivatives in the morning (fasting samples)	30 weeks after randomization

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Groupement Interrégional de Recherche Clinique et d'Innovation; Région Nord-Pas de Calais, France; Laboratory of excellence DISTALZ; Meo coffee
• Investigators: Principal Investigator: Thibaud LEBOUVIER, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's disease; caffeine; cognitive impairment
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• Other Study ID Numbers: 2018_95; 2019-002360-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No