Effects of Melatonin in Untreated Obstructive Sleep Apnea

Study Overview
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Brief Summary
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The investigators have previously shown that 1 week of 10mg Melatonin improves sleep consolidation in untreated obstructive sleep apnea (OSA) patients. This study aims to extend on those findings to determine if longer treatment of Melatonin improves other outcomes in untreated OSA patients.

Detailed Description
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Intermittent hypoxia (low oxygen), sleep fragmentation and restriction are characteristic of obstructive sleep apnea (OSA) and cause mental deficits and cardiovascular disease (CVD). Melatonin (MLT) is a hormone with sleep promoting properties and the investigators have found 7 days 10mg MLT treatment significantly increases sleep consolidation in untreated OSA. Thus, melatonin could improve mental function. MLT also has potent antioxidant, anti-inflammatory and anti-hypertensive properties. In humans with CVD and metabolic disorder exogenous MLT improves a wide range of cardio-metabolic outcomes. In rat models of OSA, MLT completely blocks intermittent hypoxia induced cardiovascular damage and brain cell death. Intermittent hypoxia also induces lasting changes in the neural control of breathing, which worsens OSA. Experimentally antioxidants block the induction of changes to neural control of breathing. Thus MLT may also normalize the control of breathing and reduce the severity of OSA. Given these findings, the hypothesis is that MLT will improve mental function, cardiovascular outcomes and control of breathing in untreated OSA.

Official Title
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Does Melatonin Improve Neurocognitive Function, Cardiovascular Outcomes and Control of Breathing in Untreated Obstructive Sleep Apnea?

Conditions
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Obstructive Sleep Apnea

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: moderate-severe OSA (AHI ≥15/hr) Exclusion Criteria: non-English speakers (due to necessity to complete neurocognitive testing) other sleep disorders history of driving or other accidents due to sleepiness or an Epworth score (ESS)> 18 pregnant smokers (quit ≥ 1 year ago acceptable) diabetes cardiac (other than hypertension), pulmonary, renal, neurologic, neuromuscular or hepatic disease Substantial alcohol (>3oz/day) or use of illicit drugs psychiatric disorders (other than depression or anxiety) current MLT use or use within last 6 months beta blockers, central nervous system depressants or stimulants, anti-inflammatories, anticoagulants, immunosuppressants, vitamins, antioxidants.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br>30 days 10mg Melatonin taken nightly 1 hour before bed | Dietary Supplement: Melatonin<br>* 30 days 10mg Melatonin taken nightly 1 hour before bed<br>|
| Placebo Comparator: Placebo<br>30 days placebo taken nightly 1 hour before bed | Other: Placebo<br>* 30 days placebo taken nightly 1 hour before bed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PHQ-9 score | 9 Questions relating to depressive symptoms. Answers to each question rank from 0-3. Minimum total score = 0, maximum total score = 27, with >=10 indicating clinically significant moderate severity depressive symptoms. | baseline versus on the 30th day of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactive Hyperemia Index | Endothelial function is calculated as the ratio between the magnitude of the mean post-occlusion pulse wave amplitude and mean baseline pulse wave amplitude. | baseline versus on the 30th day of treatment |