Melatonin for Huntington's Disease (HD) Gene Carriers With HD Related Sleep Disturbance - a Pilot Study

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of exogenous melatonin in improving sleep quality in HD gene carriers.

Official Title
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Melatonin for Huntington's Disease (HD) Gene Carriers With HD Related Sleep Disturbance - a Pilot Study

Conditions
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Huntington Disease

Intervention / Treatment
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* Dietary Supplement: Melatonin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Verified HD mutation carriers. Patients who report sleep disturbance as measured by a score ≥5 on the Pittsburgh Sleep Quality Index (PSQI); Stable concomitant medication (no change of medication during last 30 days prior to inclusion); Written informed consent by prospective study participant before conduct of any trial-related procedure; Participant must be able to make an informed decision of whether or not to participate in the study. Exclusion Criteria: Pregnant or nursing women; Woman of childbearing potential, not using highly effective methods of contraception such as oral, topical or injected contraception, intrauterine device (IUD), contraceptive vaginal ring, or double barrier method such as diaphragm and condom with spermicide) or not surgically sterile (via hysterectomy, ovariectomy or bilateral tubal ligation) or not at least one year post menopausal; Presence of any medically not controllable disease (e.g. uncontrolled arterial hypertension or diabetes mellitus); Use of benzodiazepines, sedating antidepressants (mirtazapine or trazodone) or sedating antipsychotics (olanzapine and quetiapine) in the previous four weeks; Severe cognitive disorders defined as a score < 18 on the MOCA; Participation in another investigative drug trial within 2 months; Subjects who are unlikely to be compliant and attend scheduled clinic visits as required as determined by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br> | Dietary Supplement: Melatonin<br>* Participants will receive melatonin 5 mg once a day (30 min prior to bedtime) for four weeks, followed by one-week washout before crossing-over.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Participants will receive placebo once a day (30 min prior to bedtime) for four weeks, followed by one-week washout before crossing-over.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PSQI) | The PSQI is a 9-question instrument used to measure the quality and patterns of sleep in adults. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of 5or greater indicates a poor sleeper. | Baseline, week 5, week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in sleep quality, as assessed by the Huntington's disease (HD) sleep questionnaire | This questionnaire contained 45 questions that focused on different sleep-related issues such as duration, quality of sleep, abnormal nocturnal behavior and quality of life. The questionnaire has a total score of 19 points, scores of (0 - 3) represent the 'normal' range whilst, scores of (4 - 6) reflect 'mild' and scores of 7 and above indicate a 'significant' sleep disturbance. | Baseline, week 5, week 9 | 
| Improvement in daytime somnolence, as evaluated by the Epworth Sleepiness Scale (ESS) | The ESS is a questionnaire designed to measure the subject's general level of daytime sleepiness. This scale scores from 0-24, with higher scores showing severe excessive daytime sleepiness. | Baseline, week 5, week 9 | 
| Improvement in self-perceived cognitive function, as assessed by the Quality of Life in Neurological Disorders questionnaire (NeuroQOLv2.0) Cognition Function - Short Form | It is an 8-question instrument designed and validated to evaluate perceived difficulties in cognitive abilities (e.g., memory, attention, and decision making, or in the application of such abilities to everyday tasks (e.g., planning, organizing, calculating, remembering and learning). The score ranges from 0-100, with higher scores meaning a better or worse outcome according to the domain evaluated. | Baseline, week 5, week 9 | 
| Improvement in global cognitive functioning, as assessed by the Montreal cognitive assessment (MoCA) | The MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. Scores on the MoCA range from zero to 30, with a score of 26 and higher generally considered normal. | Baseline, week 5, week 9 | 
| Improvement in quality of life, as evaluated by the Huntington's Disease Quality of Life Questionnaire (HDQoL) | It is a disease-specific scale containing 40 questions, with answers including different types of frequency from never to all of the time. | Baseline, week 5, week 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington's Disease, Melatonin