Effects of Melatonin in Untreated Obstructive Sleep Apnea

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

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.

Study Overview

• Status: Terminated
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Dietary supplement: Melatonin; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoxic ventilatory response	change in ventilation per change in expiratory CO2 during sustained hypoxia	baseline versus on the 30th day of treatment

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: April 2, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 180013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No