Clinical trial NCT04570085: Effect of CAFfeine on Cognition in Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
caffeine
cognitive impairment
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Groupement Interrégional de Recherche Clinique et d'Innovation
name: Laboratory of excellence DISTALZ
name: Région Nord-Pas de Calais, France
name: Meo coffee
First posted: 2020-09-30
Enrollment: 248
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Changes in NTB scores
timeFrame: 30 weeks after randomization
Secondary outcomes:
measure: Caffeine treatment effect on MMSE score
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on NTB subscores
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on TAP scores
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on Epworth score
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on DAD-6 score
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on QoL-AD score
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on CGIC score
timeFrame: 30 weeks after randomization
measure: Caffeine treatment effect on Zarit score
timeFrame: 30 weeks after randomization
measure: persistent effect of caffeine treatment on MMSE score after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period
timeFrame: 36 weeks after randomization
measure: Caffeine effect heterogeneity: impact of AD treatment
timeFrame: 30 weeks after randomization
measure: Caffeine effect heterogeneity: impact of ApoE4 status
timeFrame: 30 weeks after randomization
measure: Caffeine effect heterogeneity: impact of caffeine metabolism speed
timeFrame: 30 weeks after randomization
measure: Caffeine effect heterogeneity: impact of gender
timeFrame: 30 weeks after randomization
measure: Caffeine safety profile: NPI scores
timeFrame: 30 weeks after randomization
measure: Caffeine safety profile: heart beat
timeFrame: 30 weeks after randomization
measure: Caffeine safety profile: blood pressure
timeFrame: 30 weeks after randomization
measure: Caffeine and its derivatives concentrations in blood samples
timeFrame: 30 weeks after randomization
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Arras
country: France
facility: CH Arras
city: Beauvais
country: France
facility: CH Beauvais
city: Béthune
country: France
facility: CH Béthune
city: Caen
country: France
facility: CHU Caen
city: Calais
country: France
facility: CH Calais
city: Dunkerque
country: France
facility: CH Dunkerque
city: Le Quesnoy
country: France
facility: CH Le Quesnoy
city: Lens
country: France
facility: CH Lens
city: Lille
country: France
facility: Hôpital Roger Salengro
city: Lille
country: France
facility: CHU Lille consultation mémoire Les Bâteliers
city: Roubaix
country: France
facility: CH Roubaix
city: Rouen
country: France
facility: CHU Rouen
city: Saint-Quentin
country: France
facility: CH Saint Quentin
city: Seclin
country: France
facility: CH Seclin
city: Tourcoing
country: France
facility: CH Tourcoing
city: Valenciennes
country: France
facility: CH Valenciennes
Study officials:
affiliation: University Hospital, Lille
name: thibaud LEBOUVIER, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: