NCT05924425

Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 62 (estimated)
• Sponsor: University Hospital, Montpellier · Academic / Other
• Sex: All
• Age: 60 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

DARIDOR-ALZ is a phase IV clinical trial designed to evaluate both the efficacy and safety of daridorexant, a selective dual orexin receptor antagonist that blocks the actions of the orexin neuropeptides at both orexin-1 and orexin-2 receptors, in selected populations of MCI and mild-to-moderate AD patients with insomnia complaints.

Detailed description

This Phase IV clinical trial is a monocentric, randomized, double-blind, placebo-controlled, 2 way-crossover study (with two periods of one month separated by a washout period range from 5 to 12 days).The study population includes MCI and mild-to-moderate AD patients aged between 60 and 85 years old, with insomnia complaints. A single-night baseline polysomnography recording will be performed from 11 pm to 7 am at the Montpellier Sleep Unit. After a baseline PSG that assessed TST \< 6 hours and WASO \> 1 hour, treatment will be assigned using an interactive response technology system. A randomization list will be generated and will remain confidential until the database is locked. Participants, investigators, and site personnel will be unaware of treatment allocation during the two crossover periods. Patients will be randomized (1:1) to receive daridorexant 50 mg or placebo, without titration, every evening within 30 minutes of going to bed during both treatment periods (Treatment Period A and B) of one-month duration each. Each treatment period will be followed by a one-week (range 5-12 days) washout period at home. A ten-month open-label (OL) study with daridorexant 50 mg will be proposed to all participants after completing the second treatment period. Based on the experience with another DORA study in patients with mild-to-moderate probable Alzheimer's disease, the investigators would need to recruit 62 patients (including drop-outs).

Conditions

• Alzheimer Disease
• Insomnia Disorder
• Sleep

Interventions

Type	Name	Description
DRUG	Daridorexant 50 mg	Patients randomized in the experimental group will receive the treatment every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home.
DRUG	Placebo	Patients randomized in the control group will receive the placebo every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home.
PROCEDURE	Polysomnography	A full-night polysomnography recording with blood pressure and heart rate monitoring will be performed at night in the Sleep Laboratory from 11 p.m. to 7 a.m. at baseline (before the randomization) and at the end of each period (Period A/M1, Period B/M2). The recording procedure consists of an electroencephalogram, two electrooculograms, an electromyogram, an electrocardiogram, and a videographic recording. This examination is painless (the sensors are glued to the skin for the duration of the recording). The advantages of this video-polysomnography are based on the evaluation of sleep architecture, micro-arousals, respiratory events and nocturnal motor behavior.
BEHAVIORAL	Neuropsychological assessment	A full neuropsychological assessment will be performed at inclusion, M1, M2
BEHAVIORAL	Questionnaires on sleep and behavioural problems	Questionnaires on sleep and behavioural problems will be performed at inclusion, M1, M2
PROCEDURE	Actimetrics	Measurement of actimetrics for seven days in average (with a minimum of three nights required) prior to the inclusion visit, M1 visit and M2 visit.
PROCEDURE	24-hour Ambulatory Blood Pressure Monitoring (ABPM	Evaluation of the 24-hour hemodynamic profile of a patient by multiple and regular blood pressure and heart rate measurements. The ABP will be monitored at inclusion, M1 and M2
OTHER	Biomarker assay	Determination of AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) in serum and cerebrospinal fluid (CSF) and dosage of Orexin-A/hypocretin-1 in the CSF

Timeline

• Start date: 2024-03-13
• Primary completion: 2026-05-13
• Completion: 2027-03-13
• First posted: 2023-06-29
• Last updated: 2024-04-11

Locations

1 site across 1 country: France