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

NCT05924425 | Recruiting Phase 4

• 1 other identifier: RECHMPL22_0529
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer Disease; Insomnia Disorder; Sleep

Keywords

Orexin; Daridorexant; Cognition; Alzheimer; Sleep; Insomnia

Outcome Measures

Primary Outcomes (1)

• Change in Total Sleep Time (TST).

  TST is defined as the total sleep time in minutes. The total sleep time is the total amount of sleep time scored during the total recording time. The TST is measured during polysomnography.

  from baseline to the end of each period A/B (Month1/Month2)

Secondary Outcomes (42)

• Change in the wake time after sleep onset (WASO)

  from baseline to the end of each period A/B (Month1/Month2)

• Change in Latency to Persistent Sleep (LPS)

  from baseline to the end of each period A/B (Month1/Month2)

• Measure of sleep time at stage 1-2 during polysomnography

  from baseline to the end of each period A/B (Month1/Month2)

• Measure of sleep time at stage 3 during polysomnography

  from baseline to the end of each period A/B (Month1/Month2)

• Measure of number of wake bouts on the whole night

  from baseline to the end of each period A/B (Month1/Month2)

Study Arms (2)

Daridorexant 50 mg

EXPERIMENTAL

Patients will receive daridorexant 50 mg during one month (Period A or Period B). Daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia.

Drug: Daridorexant 50 mg; Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetrics; Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM; Other: Biomarker assay

Placebo-controlled arm

PLACEBO COMPARATOR

Patients will receive a placebo matching to daridorexant 50 mg during one month (Period A or Period B).

Drug: Placebo; Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetrics; Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM; Other: Biomarker assay

Interventions

Daridorexant 50 mg DRUG

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.

Daridorexant 50 mg

Placebo DRUG

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.

Placebo-controlled arm

Polysomnography PROCEDURE

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.

Daridorexant 50 mg; Placebo-controlled arm

Neuropsychological assessment BEHAVIORAL

A full neuropsychological assessment will be performed at inclusion, M1, M2

Daridorexant 50 mg; Placebo-controlled arm

Actimetrics PROCEDURE

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.

Daridorexant 50 mg; Placebo-controlled arm

24-hour Ambulatory Blood Pressure Monitoring (ABPM PROCEDURE

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

Daridorexant 50 mg; Placebo-controlled arm

Biomarker assay OTHER

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

Daridorexant 50 mg; Placebo-controlled arm

Questionnaires on sleep and behavioural problems BEHAVIORAL

Questionnaires on sleep and behavioural problems will be performed at inclusion, M1, M2

Daridorexant 50 mg; Placebo-controlled arm

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \[60-85\] years old
• Outpatients
• Pre-screening:
• Complaints of dissatisfaction with sleep quantity or quality, despite adequate opportunity for sleep, at least 3 nights per week and for at least 3 months, and
• Total sleep time causes clinically significant distress or impairment in daytime functioning, and
• Total sleep time estimated by interview was below 6 hours, on at least 3 nights per week and for at least 1 month before screening
• Baseline PSG (at randomization) assessed TST \< 6 hours and WASO \> 1 hour
• Diagnosis of MCI and AD patients at an early stage according to the NIA diagnosis criteria (core clinical criteria for MCI, positive biomarker for CSF Aβ42 and neuronal injury (hippocampal and/or temporal atrophy by MRI))
• MMSE from 12 to 26
• Clinical Dementia Rating CDR from 0.5 to 2
• Possible of CNS drugs if stable dose for at least 3 months: anticholinesterase drugs (rivastigmine, donepezil, galantamine) or memantine
• For a male subject who is not sterilized and is sexually active with a female partner of childbearing potential, no contraceptive methods are needed
• Patients significantly dependent on caregivers
• Institutionalized patients
• Analphabetism or subjects unable to read or/and write

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: collaborator
• University Hospital, Montpellier: lead

Study Sites (1)

University Hospital, Montpellier

Montpellier, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Sleep Initiation and Maintenance Disorders

Interventions

daridorexant; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Yves Dauvilliers, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yves Dauvilliers, MD

CONTACT

+33467336361; y-dauvilliers@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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 (Period A and Period B)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: During Period A, 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 will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the placebo. During Period A, 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 will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the daridorexant 50 mg.

Study Record Dates

• First Submitted: June 4, 2023
• First Posted: June 29, 2023
• Study Start: March 13, 2024
• Primary Completion (Estimated): May 13, 2027
• Study Completion (Estimated): March 13, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-03

Locations

FR (1)