MedPath

Effect of CAFfeine on Cognition in Alzheimer's Disease

Phase 3
Recruiting
Conditions
Alzheimer Disease
Interventions
Drug: Placebo
Registration Number
NCT04570085
Lead Sponsor
University Hospital, Lille
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
248
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CaffeineCaffeineafter a 3 weeks up titration period, 1 capsule of 200 mg twice a day during 27 weeks (ie 400mg/day)
placeboPlaceboafter a 3 weeks up titration period, 2 capsules per day during 27 weeks
Primary Outcome Measures
NameTimeMethod
Changes in NTB scores30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment

Secondary Outcome Measures
NameTimeMethod
Caffeine treatment effect on TAP scores30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on TAP scores

persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period36 weeks after randomization

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

Caffeine effect heterogeneity: impact of caffeine metabolism speed30 weeks after randomization

impact of caffeine metabolism on caffeine effect

persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period36 weeks after randomization

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

Caffeine treatment effect on Epworth score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on Epworth score

Caffeine treatment effect on QoL-AD score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on QoL-AD score

Caffeine treatment effect on DAD-6 score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on DAD-6 score

persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period36 weeks after randomization

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

Caffeine treatment effect on MMSE score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on MMSE score

Caffeine treatment effect on CGIC score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on CGIC score

Caffeine treatment effect on Zarit score30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on Zarit score

persistent effect of caffeine treatment on MMSE score after a 6 weeks wash out period36 weeks after randomization

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

persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period36 weeks after randomization

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

Caffeine effect heterogeneity: impact of gender30 weeks after randomization

impact of gender on caffeine effect

Caffeine treatment effect on NTB subscores30 weeks after randomization

difference between randomized value and value after 30 weeks of treatment on NTB subscores

persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period36 weeks after randomization

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

Caffeine safety profile: NPI scores30 weeks after randomization

changes in NPI scores and subscores between caffeine and placebo arms

Caffeine safety profile: heart beat30 weeks after randomization

changes in heart beat between caffeine and placebo arms

persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period36 weeks after randomization

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

Caffeine effect heterogeneity: impact of AD treatment30 weeks after randomization

impact of AD treatment on caffeine effect

Caffeine effect heterogeneity: impact of ApoE4 status30 weeks after randomization

impact of ApoE4 status on caffeine effect

Caffeine safety profile: blood pressure30 weeks after randomization

changes in blood pressure between caffeine and placebo arms

Caffeine and its derivatives concentrations in blood samples30 weeks after randomization

increase in caffeinemia and its derivatives in the morning (fasting samples)

Trial Locations

Locations (17)

CH Béthune

🇫🇷

Béthune, France

CHU Caen

🇫🇷

Caen, France

CHU Amiens

🇫🇷

Amiens, France

CH Arras

🇫🇷

Arras, France

CH Beauvais

🇫🇷

Beauvais, France

CH Calais

🇫🇷

Calais, France

CH Dunkerque

🇫🇷

Dunkerque, France

CH Le Quesnoy

🇫🇷

Le Quesnoy, France

Hôpital Roger Salengro

🇫🇷

Lille, France

CH Lens

🇫🇷

Lens, France

CHU Lille consultation mémoire Les Bâteliers

🇫🇷

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, France

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