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NCT Number: NCT04570085

Effect of CAFfeine on Cognition in Alzheimer's Disease

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).

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Key information

Conditions

Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU Amiens, Amiens, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Caffeine

Drug

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

Drug

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.

Primary outcomes

  1. Changes in NTB scores

    Time frame: 30 weeks after randomization

    difference between randomized value and value after 30 weeks of treatment

Secondary outcomes

  1. Caffeine treatment effect on MMSE score

    Time frame: 30 weeks after randomization

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

  2. Caffeine treatment effect on NTB subscores

    Time frame: 30 weeks after randomization

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

  3. Caffeine treatment effect on TAP scores

    Time frame: 30 weeks after randomization

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

  4. Caffeine treatment effect on Epworth score

    Time frame: 30 weeks after randomization

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

  5. Caffeine treatment effect on DAD-6 score

    Time frame: 30 weeks after randomization

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

  6. Caffeine treatment effect on QoL-AD score

    Time frame: 30 weeks after randomization

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

  7. Caffeine treatment effect on CGIC score

    Time frame: 30 weeks after randomization

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

  8. Caffeine treatment effect on Zarit score

    Time frame: 30 weeks after randomization

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

  9. persistent effect of caffeine treatment on MMSE score after a 6 weeks wash out period

    Time frame: 36 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

  10. persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period

    Time frame: 36 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

  11. persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period

    Time frame: 36 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

  12. persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period

    Time frame: 36 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

  13. persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period

    Time frame: 36 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

  14. persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period

    Time frame: 36 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

  15. persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period

    Time frame: 36 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

  16. Caffeine effect heterogeneity: impact of AD treatment

    Time frame: 30 weeks after randomization

    impact of AD treatment on caffeine effect

  17. Caffeine effect heterogeneity: impact of ApoE4 status

    Time frame: 30 weeks after randomization

    impact of ApoE4 status on caffeine effect

  18. Caffeine effect heterogeneity: impact of caffeine metabolism speed

    Time frame: 30 weeks after randomization

    impact of caffeine metabolism on caffeine effect

  19. Caffeine effect heterogeneity: impact of gender

    Time frame: 30 weeks after randomization

    impact of gender on caffeine effect

  20. Caffeine safety profile: NPI scores

    Time frame: 30 weeks after randomization

    changes in NPI scores and subscores between caffeine and placebo arms

  21. Caffeine safety profile: heart beat

    Time frame: 30 weeks after randomization

    changes in heart beat between caffeine and placebo arms

  22. Caffeine safety profile: blood pressure

    Time frame: 30 weeks after randomization

    changes in blood pressure between caffeine and placebo arms

  23. Caffeine and its derivatives concentrations in blood samples

    Time frame: 30 weeks after randomization

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

Study contacts

Contact information is provided by the study sponsor or research team.

Thibaud LEBOUVIER, MD,PhD

CONTACT

[email protected]

03 20 44 60 21 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Lille

Other

Collaborators

  • Groupement Interrégional de Recherche Clinique et d'Innovation
  • Laboratory of excellence DISTALZ
  • Meo coffee
  • Région Nord-Pas de Calais, France

Registry information

Official study 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

Acronym: CAFCA

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Sep 30, 2020
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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