Alzheimer Disease
Conditions
Keywords
Alzheimer's disease, caffeine, cognitive impairment
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).
Interventions
DRUGCaffeine
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.
DRUGPlacebo
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.
Sponsors
University Hospital, Lille
Groupement Interrégional de Recherche Clinique et d'Innovation
Laboratory of excellence DISTALZ
Région Nord-Pas de Calais, France
Meo coffee
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in NTB scores | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Caffeine treatment effect on MMSE score | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on MMSE score |
| Caffeine treatment effect on NTB subscores | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on NTB subscores |
| Caffeine treatment effect on TAP scores | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on TAP scores |
| Caffeine treatment effect on Epworth score | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on Epworth score |
| Caffeine treatment effect on DAD-6 score | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on DAD-6 score |
| Caffeine treatment effect on QoL-AD score | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on QoL-AD score |
| Caffeine treatment effect on CGIC score | 30 weeks after randomization | difference between randomized value and value after 30 weeks of treatment on CGIC score |
| Caffeine treatment effect on Zarit score | 30 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 period | 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 |
| persistent effect of caffeine treatment on NTB subscores after a 6 weeks wash out period | 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 |
| persistent effect of caffeine treatment on TAP scores after a 6 weeks wash out period | 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 |
| persistent effect of caffeine treatment on Epworth score after a 6 weeks wash out period | 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 |
| persistent effect of caffeine treatment on DAD-6 score after a 6 weeks wash out period | 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 |
| persistent effect of caffeine treatment on QoL-AD score after a 6 weeks wash out period | 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 |
| persistent effect of caffeine treatment on Zarit score after a 6 weeks wash out period | 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 |
| Caffeine effect heterogeneity: impact of AD treatment | 30 weeks after randomization | impact of AD treatment on caffeine effect |
| Caffeine effect heterogeneity: impact of ApoE4 status | 30 weeks after randomization | impact of ApoE4 status on caffeine effect |
| Caffeine effect heterogeneity: impact of caffeine metabolism speed | 30 weeks after randomization | impact of caffeine metabolism on caffeine effect |
| Caffeine effect heterogeneity: impact of gender | 30 weeks after randomization | impact of gender on caffeine effect |
| Caffeine safety profile: NPI scores | 30 weeks after randomization | changes in NPI scores and subscores between caffeine and placebo arms |
| Caffeine safety profile: heart beat | 30 weeks after randomization | changes in heart beat between caffeine and placebo arms |
| Caffeine safety profile: blood pressure | 30 weeks after randomization | changes in blood pressure between caffeine and placebo arms |
| Caffeine and its derivatives concentrations in blood samples | 30 weeks after randomization | increase in caffeinemia and its derivatives in the morning (fasting samples) |
Countries
France
Contacts
CONTACTThibaud LEBOUVIER, MD,PhD
PRINCIPAL_INVESTIGATORthibaud LEBOUVIER, MD,PhD
University Hospital, Lille
Outcome results
None listed