Effect of CAFfeine on Cognition in Alzheimer's Disease

Alzheimer Disease Clinical Trial

— CAFCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04570085
• Other study ID #: 2018_95
• Secondary ID: 2019-002360-27
• Status: Recruiting
• Phase: Phase 3
• Start date: March 1, 2021
• Est. completion date: November 2024

Study information

• Verified date: February 2022
• Source: University Hospital, Lille
• Contact: Thibaud LEBOUVIER, MD,PhD
• Phone: 03 20 44 60 21
• Email: thibaud.lebouvier[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

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
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.

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CH Arras	Arras
France	CH Beauvais	Beauvais
France	CH Béthune	Béthune
France	CHU Caen	Caen
France	CH Calais	Calais
France	CH Dunkerque	Dunkerque
France	CH Le Quesnoy	Le Quesnoy
France	CH Lens	Lens
France	CHU Lille consultation mémoire Les Bâteliers	Lille
France	Hôpital Roger Salengro	Lille
France	CH Roubaix	Roubaix
France	CHU Rouen	Rouen
France	CH Saint Quentin	Saint-Quentin
France	CH Seclin	Seclin
France	CH Tourcoing	Tourcoing
France	CH Valenciennes	Valenciennes

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Lille	Groupement Interrégional de Recherche Clinique et d'Innovation, Laboratory of excellence DISTALZ, Meo coffee, Région Nord-Pas de Calais, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in NTB scores	difference between randomized value and value after 30 weeks of treatment	30 weeks after randomization
Secondary	Caffeine treatment effect on MMSE score	difference between randomized value and value after 30 weeks of treatment on MMSE score	30 weeks after randomization
Secondary	Caffeine treatment effect on NTB subscores	difference between randomized value and value after 30 weeks of treatment on NTB subscores	30 weeks after randomization
Secondary	Caffeine treatment effect on TAP scores	difference between randomized value and value after 30 weeks of treatment on TAP scores	30 weeks after randomization
Secondary	Caffeine treatment effect on Epworth score	difference between randomized value and value after 30 weeks of treatment on Epworth score	30 weeks after randomization
Secondary	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
Secondary	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
Secondary	Caffeine treatment effect on CGIC score	difference between randomized value and value after 30 weeks of treatment on CGIC score	30 weeks after randomization
Secondary	Caffeine treatment effect on Zarit score	difference between randomized value and value after 30 weeks of treatment on Zarit score	30 weeks after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Caffeine effect heterogeneity: impact of AD treatment	impact of AD treatment on caffeine effect	30 weeks after randomization
Secondary	Caffeine effect heterogeneity: impact of ApoE4 status	impact of ApoE4 status on caffeine effect	30 weeks after randomization
Secondary	Caffeine effect heterogeneity: impact of caffeine metabolism speed	impact of caffeine metabolism on caffeine effect	30 weeks after randomization
Secondary	Caffeine effect heterogeneity: impact of gender	impact of gender on caffeine effect	30 weeks after randomization
Secondary	Caffeine safety profile: NPI scores	changes in NPI scores and subscores between caffeine and placebo arms	30 weeks after randomization
Secondary	Caffeine safety profile: heart beat	changes in heart beat between caffeine and placebo arms	30 weeks after randomization
Secondary	Caffeine safety profile: blood pressure	changes in blood pressure between caffeine and placebo arms	30 weeks after randomization
Secondary	Caffeine and its derivatives concentrations in blood samples	increase in caffeinemia and its derivatives in the morning (fasting samples)	30 weeks after randomization