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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-13

Study Completion Date

2027-03-13

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Daridorexant for Alzheimer Disease Prevention

NCT07213349

Alzheimer Disease (AD)

RECRUITING PHASE2

Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

NCT03001557

Irregular Sleep-Wake Rhythm Disorder

COMPLETED PHASE2

Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With an Acetylcholinesterase Inhibitor

NCT02006654

Alzheimer's Disease

COMPLETED PHASE3

Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With Donepezil

NCT01955161

Alzheimer's Disease

COMPLETED PHASE3

Clinical Trial to Determine Tolerable Dosis of Vorinostat in Patients With Mild Alzheimer Disease

NCT03056495

Alzheimer Disease

TERMINATED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Alzheimer Disease Insomnia Disorder Sleep

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

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)

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Daridorexant 50 mg

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.

Group Type EXPERIMENTAL

Daridorexant 50 mg

Intervention Type 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.

Polysomnography

Intervention Type 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.

Neuropsychological assessment

Intervention Type BEHAVIORAL

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

Questionnaires on sleep and behavioural problems

Intervention Type BEHAVIORAL

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

Actimetrics

Intervention Type 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.

24-hour Ambulatory Blood Pressure Monitoring (ABPM

Intervention Type 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

Biomarker assay

Intervention Type 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

Placebo-controlled arm

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Polysomnography

Intervention Type 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.

Neuropsychological assessment

Intervention Type BEHAVIORAL

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

Questionnaires on sleep and behavioural problems

Intervention Type BEHAVIORAL

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

Actimetrics

Intervention Type 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.

24-hour Ambulatory Blood Pressure Monitoring (ABPM

Intervention Type 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

Biomarker assay

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Neuropsychological assessment

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

Intervention Type BEHAVIORAL

Questionnaires on sleep and behavioural problems

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

Intervention Type BEHAVIORAL

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.

Intervention Type 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

Intervention Type PROCEDURE

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

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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 and sleep diary was below 6 hours, on at least 3 nights per week and for at least 1 month before screening, and
* Insomnia Severity Scale ISI© score ≥ 15
* 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
* Patients unable to perform the neuropsychological tests
* Patients unable to complete the study instruments (sleep diary)
* Planned longer stay outside the region that prevents compliance with the visit schedule
* Patients who cannot be followed up for at least 2 months
* History of narcolepsy and/or cataplexy
* History of drug or alcohol abuse or addiction
* History of depression or suicidal ideation/attempt or other psychiatric conditions
* Moderate and severe liver failure
* PSG baseline evidence of significant/severe sleep-related breathing disorder (defined as \>30 apnea/hypopnea episodes per hour)
* Treatments interfering with sleep-wake patterns
* Psychotropic drugs: antidepressants (SSRI (e.g. fluoxetine, sertraline, paroxetine…), SNRI (e.g. venlafaxine, duloxetine)), neuroleptics (e.g. clozapine, olanzapine, aripiprazole...), and hypnotics (benzodiazepines, zolpidem, zopiclone) or drug for pain (level 2 (e.g. codeine, tramadol), and level 3 (morphine and derivatives))
* Hypersensitivity to the active substance or to any of the excipients listed in the Summary of Product Characteristics (SmPC)
* Forbidden and restricted concomitant medications:

* Concomitant CNS-depressant medicinal products
* CYP3A4 inhibitors
* CYP3A4 inducers
* Participation in another clinical trial or administration of an investigational product
* Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship).
* Subjects not covered by public health insurance
* Failure to obtain written informed consent after a reflection period

Minimum Eligible Age

60 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No