The Effect of Melatonin Upon Post-Acute Withdrawal Among Males in a Residential Treatment Program

Study Overview
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Brief Summary
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Individuals recovering from drug and/or alcohol addiction initially experience the symptoms of acute withdrawal before experiencing the symptoms of post-acute withdrawal (PAWS). PAWS include a wide array of emotional and psychological symptoms such as anxiety, sleep disturbances, depression, and stress. Previous studies have shown that melatonin therapy was beneficial to alleviate anxiety, depressive symptoms, and sleep disturbances. However, no randomized, double-blind, placebo controlled trials have been conducted in males who are experiencing PAWS. The purpose of this study is to investigate the effect of 5 mg melatonin given nightly for four weeks on weekly assessed, self-reported anxiety, depressive symptoms, insomnia, and stress in males with PAWS who reside in a residential treatment center.

Detailed Description
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Approval was obtained from the Institutional Review Board at Duquesne University prior to the study implementation. The trial was a single-center, randomized, double-blind, matched placebo-controlled, parallel-group trial conducted in males 18 years of age and older who are in a residential treatment program for chemical dependency at the Salvation Army Harbor Light Center (865 West North Avenue, Pittsburgh, Pennsylvania, 15233) in the United States of America. Convenience sampling was used to recruit individuals from July 2015 to December 2015. A total sample of 70 participants were enrolled and block randomized with an allocation ratio of 1:1 for the interventions. Financial compensation of $5.00 U.S. was initiated at Day 7 and continued at each follow-up (Day 14, Day 21 & Day 28). Intention-to-treat and complete case analyses were conducted. No interim analysis was performed to assess efficacy. Participants completed study materials in a designated room at the center. Briefly, this study involved the completion of four validated surveys assessing self-reported perceived severity of anxiety (Generalized Anxiety Disorder Scale; GAD-7), depression (Personal Health Questionnaire Depression Scale; PHQ-8), stress (Perceived Stress Scale; PSS-14), sleep complaints and how is sleep affecting daily life (Pittsburgh Sleep Symptom Questionnaire - Insomnia; PSSQ-1) at five time points (Baseline, Day 7, Day 14, Day 21, and Day 28). To address any adverse events relating to the interventions, the participant was encouraged to report any perceived adverse events to the investigator. To protect the anonymity and confidentiality of the participants, all paperwork were de-identified but contained their unique identification number.

Official Title
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The Effect of Melatonin Upon Post-Acute Withdrawal Among Males in a Residential Treatment Program: A Randomized, Double Blind, Placebo, Controlled Trial

Conditions
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Substance Withdrawal Syndrome

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males 18 years of age and older who are actively participating in therapy at a residential treatment program Willingness to participate in the 4-week study Willingness to provide self-reported demographic, social, medical, medication, preventive, and mental health histories Willingness to complete self-assessments of anxiety, depression, insomnia, and stress at designated time intervals Willingness to administer daily before bed a capsule containing either 5 mg melatonin plus vegetable fiber filler or only the vegetable fiber filler without melatonin (i.e., the matched placebo). English speaking Exclusion Criteria: Patients already taking melatonin Adverse history with melatonin supplementation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>capsule containing 5mg melatonin plus cellulose | Dietary Supplement: Melatonin<br>* 5 mg capsule p.o. at bedtime daily<br>* Other names: N-acetyl-5-methoxytryptamine;|
| Placebo Comparator: Matched Placebo<br>capsule containing cellulose | Dietary Supplement: Matched Placebo<br>* 5 mg capsule p.o. at bedtime daily<br>* Other names: Vegetable fiber;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of melatonin or placebo on the change in anxiety as measured by the Generalized Anxiety Disorder (GAD-7) scale | The GAD-7 assesses the perceived severity of anxiety through a 7-item scale that assesses anxiety as measured by a symptom checklist over the last two weeks. It employs a four point scale with the response options Not at all (0 pts), Several days (1 pt), More than half the days (2 pts), and Nearly every day (3 pts). Severity is based on the sum total where 15 - 21 is considered severe anxiety. The GAD-7 also asks a question about how difficult have these problems contributed to the activities of daily living, responses range from Not difficult at all to Extremely difficult. | Baseline, Day 7, Day 14, Day 21, Day 28 | 
| The effect of melatonin or placebo on the change in depressive symptoms as measured by the Personal Health Questionnaire Depression Scale (PHQ-8) | The PHQ-8 assesses the perceived degree of depression through an 8-item scale that assesses if the individual indicates symptoms over the last two weeks. It employs a four point scale with the response options Not at all (0 pts), Several days (1 pt), More than half the days (2 pts), and Nearly every day (3 pts). The higher the sum total the greater the degree of depression; for example, a score of ≥20 is considered severe major depression. | Baseline, Day 7, Day 14, Day 21, Day 28 | 
| The effect of melatonin or placebo on the change in sleep symptoms as measured by the Pittsburgh Sleep Symptom Questionnaire - Insomnia (PSSQ-1) | It is a 13-item scale with two subscales: Sleep complaints and How sleep is affecting daily life and assesses their experience during the past month. It employs a six point scale to assess for Sleep complaints with response options Never (0 pts), Do not know (1 pt), Rarely (2 pts), Sometimes (3 pts), Frequently (4 pts) and Always (5 pts). It employs a five point scale to assess for How sleep is affecting daily life, with the response options Not at all (0 pts), A little bit (1 pt), Moderately (2 pts), Quite a bit (3 pts), and Extremely (4 pts). If all criterion questions result in a Yes, then one can assign a diagnosis of insomnia disorder. | Baseline, Day 7, Day 14, Day 21, Day 28 | 
| The effect of melatonin or placebo on the change in stress as measured by the Perceived Stress Scale (PSS-14) | The PSS-14 assesses the perceived stress through a 14-item scale that asks about the thoughts and feelings of the individual during the past month. It employs a five point scale with the response options Never (0 pts), Almost Never (1 pt), Sometimes (2 pts), Fairly Often (3 pts), and Very Often (4 pts). In scoring the scale, scores are obtained by reversing the scores on items 4, 5, 6, 7, 9, 10, and 13 because these questions are positively stated items. The scores are summed with higher score indicating more perceived stress. | Baseline, Day 7, Day 14, Day 21, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient health histories (social, medical, medication, preventive, and mental health) | Patient health histories were used to collect key information that may be used to further identify relevant data that have the potential be used to formulate other studies that the self-reported scales do not assess. Also, the histories were used to measure the effect of confounding and moderating factors. | Baseline | 
| The number of reported adverse effects |  | Day 7, Day 14, Day 21, Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melatonin, Post-acute withdrawal symptoms, Anxiety, Depression, Insomnia, Stress, Substance withdrawal syndrome