CAFFEINE for Alzheimer's disease

Inclusion criteria

• {"criterion_text":"- Men and / or women"}
• {"criterion_text":"- Age> 50 at inclusion"}
• {"criterion_text":"- Dementia related to probable Alzheimer's disease according to the criteria of the National Institute on Aging-Alzheimer's Association; the diagnosis must be supported by brain imaging (CT or MRI) and a blood test (including ionogram, renal and hepatic function, calcemia, CRP, TSH, B12 vitamins and folate) performed in routine care"}
• {"criterion_text":"- MMSE score between 16 and 26 (terminals included)"}
• {"criterion_text":"- Presence of a partner informing and helping> 10h / week"}
• {"criterion_text":"- If the participant is being treated with acetylcholine esterase inhibitors (AChEIs) and/or memantine, the treatment must be at an effective and stable dose for 2 months prior to the screening visit and must remain stable for the duration of the study"}
• {"criterion_text":"- Patient giving written consent"}
• {"criterion_text":"- Social insured patient"}
• {"criterion_text":"- Patient willing to comply with all procedures of the study and its duration"}

Exclusion criteria

• {"criterion_text":"- Patients refusing to adopt a diet low in caffeine (eviction of tea, caffeinated sodas, chocolate in large quantities)"}
• {"criterion_text":"- CAFCA-MRI and CAFCA-TEP ancillary studies: Patients with a contraindication for MRI and / or PET scans"}
• {"criterion_text":"- Participation in an interventional therapeutic trial"}
• {"criterion_text":"- Non native French-speaking patient or illiterate."}
• {"criterion_text":"- For women of childbearing age: pregnancy in progress or planned (A pregnancy test will be performed)"}
• {"criterion_text":"- Patients taking prohibited treatment: -\tPsychotropic treatments (antidepressants, euroleptics, anxiolytics, hypnotics and mood regulators) introduced or modified <2 months before inclusion -\tChronic intake of drugs inducing or inhibiting CYP1A2 -\tInhibitory drugs: Artemisinin, Atazanavir, Cimetidine, Ciprofloxacin, Enoxacin, Ethinyl Estradiol, Fluvoxamine, Mexiletine, Thiabendazole, Norfloxacine, Stiripentol -\tInducing drugs: Barbiturates, Carbamazepine, Primidone, Rifampicin -\tAll specialties containing caffeine: ACTRON®, ALEPSAL®, ALGODOL CAFEINE®, ANTIGRIPPINE A®, ASPRO CAFEINE®, CEFALINE HAUTH®, COOPER® COFFEE CITRATE, CLARADOL CAFEINE®, GCFORM®, GURONSAN®, GYNERGENE CAFEINE® , LAMALINE®, MERCALM®, METASPIRINE®, PARACETAMOL / CAFEIN / CODEINE MYLAN®, PERCUTAFEINE®, PRONTALGINE® -\tDrugs that influence the metabolism of caffeine (after 2): quinolones, antiarrhythmics (Mexiletine, Diltiazem, Verapamil), fluvoxamine (antidepressant), omeprazole (proton pump inhibitor), Furafylline and Theophylline (bronchodilators) -\tDrugs likely to interact with caffeine: in the class of anti-epileptics: Carbamazepine, Diazepam, Phenytoin, Ethosuximide, Valproate, Gabapentin, Topiramate, Lithium"}
• {"criterion_text":"- CAFCA-MRI and CAFCA-TEP ancillary studies: Patients with a contraindication for MRI and / or PET scans"}
• {"criterion_text":"- Current major depressive episode according to DSM-5 criteria"}
• {"criterion_text":"- Other chronic pathology of the central nervous system"}
• {"criterion_text":"- Major anxiety according to the clinician (in coherence with the corresponding NPI-R items which must indicate a gravity> 2 and a repercussion> 3)"}
• {"criterion_text":"- Sleep disorders defined by gravity> 2 and a repercussion> 3 on the NPI-R; a patient paired for OSAS may be included if the equipment has been in use for> 3 months and is well tolerated (stable)"}
• {"criterion_text":"- Decompensated heart disease or severe rhythm disorder (excluding slow, treated and stable chronic atrial fibrillation)"}
• {"criterion_text":"- Any significant comorbidity that may be confounding by the clinician"}
• {"criterion_text":"- Active smoking"}
• {"criterion_text":"- Excessive alcohol consumption (> 3 units per day on average)"}

Primary endpoints

• {"endpoint_text":"- Variation in total NTB score (z-score) at 30 weeks post-randomization (difference between randomized value and value after 30 weeks of treatment)","definition_or_measurement_approach":"Total NTB z-score measured at randomization and at 30 weeks post-randomization; primary outcome is the difference (variation) between baseline and 30-week value."}

Secondary endpoints

• {"endpoint_text":"- For evaluation of the effect of caffeine compared to placebo 30 weeks after randomization 1.1)\tOn cognitive functions, variation between baseline (randomization) and V5 (30 weeks after randomization) of the following parameters: -\tMMSE score -\tNTB executive functions sub-score -\tNTB memory sub-score o Simple reaction time to TAP test -\tComplex reaction time in the TAP test o Epworth score 1.2) Functional autonomy, variation between the baseline and V4 (30 weeks after randomisation) of the DAD","definition_or_measurement_approach":"Variation between baseline and V5 (30 weeks) for cognitive measures (MMSE, NTB sub-scores, TAP reaction times, Epworth); functional autonomy variation between baseline and V4 (30 weeks) measured by DAD."}
• {"endpoint_text":"- To evaluate the persistent effect of caffeine treatment 6 weeks after its interruption (visit V5, 36 weeks after randomisation): variation of the previous parameters (except the CGIC score) between the baseline and V5 ; CGIC score at V5","definition_or_measurement_approach":"Assessment at 36 weeks (6 weeks after treatment stop) comparing baseline to V5 for prior parameters; includes CGIC score measured at V5."}
• {"endpoint_text":"- Heterogeneity of the effect of caffeine treatment On the following pre-defined subgroups: iAChE treatment (yes / no), APOE4 genotype (homo / hetero / null), caffeine metabolism (slow / fast) and gender (male / female); the variation of the NTB score (main criterion) between the baseline and the V4 visit.","definition_or_measurement_approach":"Pre-specified subgroup analyses: compare NTB score variation between baseline and V4 across subgroups defined by iAChE treatment status, APOE4 genotype, caffeine metabolism phenotype, and gender."}
• {"endpoint_text":"- Evaluate the effect of caffeine compared to placebo on the occurrence of adverse events during follow-up (from randomization to visit V5) Evolution during follow-up of NPI scores, NPI-R sleep, NPI-R anxiety, heart rate, blood pressure.","definition_or_measurement_approach":"Safety assessment from randomization to V5: record adverse events and monitor evolution of NPI scores, NPI-R sleep/anxiety subscales, heart rate and blood pressure."}
• {"endpoint_text":"- Evaluate the effect of caffeine compared to placebo on the increase of caffeine and its three dimethylated metabolites (paraxanthine, theophylline, theobromine) in the morning on an empty stomach Evolution during the monitoring of the value of caffeine and the concentration of its three dimethylated metabolites (paraxanthine, theophylline, theobromine) in the morning on an empty stomach.","definition_or_measurement_approach":"Pharmacokinetic/biomarker monitoring: morning fasting blood concentrations of caffeine and metabolites (paraxanthine, theophylline, theobromine) over follow-up."}

France

Latest Decision Or Authorization Date

12-08-2025

Number Of Sites

20

Number Of Participants

248

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Lille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Meo Fichaux","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"GIRCI Nord-Ouest","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Laboratoire d'excellence DISTALZ","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Conseil régional Hauts-de-France","duties_or_roles":"Monetary support","organisation_type":""}