Effects of Melatonin in Untreated Obstructive Sleep Apnea

• ClinicalTrials.gov Identifier: NCT03492736
• Recruitment Status: Terminated
• First Posted: April 10, 2018
• Last Update Posted: January 31, 2019
• Sponsor: Naomi Deacon
• Information provided by (Responsible Party): Naomi Deacon, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea	Dietary Supplement: Melatonin; Other: Placebo	Early Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, parallel
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Does Melatonin Improve Neurocognitive Function, Cardiovascular Outcomes and Control of Breathing in Untreated Obstructive Sleep Apnea?
• Actual Study Start Date: April 1, 2018
• Actual Primary Completion Date: October 1, 2018
• Actual Study Completion Date: October 1, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Melatonin; 30 days 10mg Melatonin taken nightly 1 hour before bed	Dietary Supplement: Melatonin; 30 days 10mg Melatonin taken nightly 1 hour before bed
Placebo Comparator: Placebo; 30 days placebo taken nightly 1 hour before bed	Other: Placebo; 30 days placebo taken nightly 1 hour before bed

Outcome Measures

Primary Outcome Measures :

1. PHQ-9 score [ Time Frame: baseline versus on the 30th day of treatment ]
   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.

Secondary Outcome Measures :

1. Reactive Hyperemia Index [ Time Frame: baseline versus on the 30th day of treatment ]
   Endothelial function is calculated as the ratio between the magnitude of the mean post-occlusion pulse wave amplitude and mean baseline pulse wave amplitude.

Other Outcome Measures:

1. Hypoxic ventilatory response [ Time Frame: baseline versus on the 30th day of treatment ]
   change in ventilation per change in expiratory CO2 during sustained hypoxia

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Groups will be matched for gender, age and BMI
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, San Diego

San Diego, California, United States, 92093

Sponsors and Collaborators

Naomi Deacon

Investigators

• Study Director: Naomi L Deacon, Ph.D.; UCSD Pulmonary and Sleep Medicine

More Information

• Responsible Party: Naomi Deacon, Research Scholar, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03492736
• Other Study ID Numbers: 180013
• First Posted: April 10, 2018
• Last Update Posted: January 31, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Melatonin; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Central Nervous System Depressants