Clinical trial NCT03492736: Effects of Melatonin in Untreated Obstructive Sleep Apnea
Official title: Does Melatonin Improve Neurocognitive Function, Cardiovascular Outcomes and Control of Breathing in Untreated Obstructive Sleep Apnea?
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Obstructive Sleep Apnea
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2018-04-10
Enrollment: 1
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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.

Primary outcomes:
measure: PHQ-9 score
timeFrame: baseline versus on the 30th day of treatment
Secondary outcomes:
measure: Reactive Hyperemia Index
timeFrame: baseline versus on the 30th day of treatment
Other outcomes:
measure: Hypoxic ventilatory response
timeFrame: baseline versus on the 30th day of treatment
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
Study officials:
affiliation: UCSD Pulmonary and Sleep Medicine
name: Naomi L Deacon, Ph.D.
role: STUDY_DIRECTOR
References: