The Effect of Melatonin on Sleep and Ventilatory Control in Obstructive Sleep Apnea

NCT02484300 | Completed

• 2 other identifiers: 150465R01HL085188
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Our hypothesis is that oxidative stress induced during repeated apneas in obstructive sleep apnea (OSA) patients alters the neural control of breathing which destabilizes ventilatory control and exacerbates OSA. Thus antioxidant treatment has the potential to reduce OSA severity. Melatonin is a hormone which regulates sleep patterns, but it is also a potent antioxidant. Melatonin production is suppressed when the eyes register light so people with healthy sleep exhibit a peak in blood serum levels around 2am which then decreases towards morning. OSA patients exhibit lower melatonin levels with a later peak around 6am which then extends later into the day. This abnormal pattern is thought to compound difficulty falling asleep and daytime mental fatigue. Therefore the potential benefits of melatonin treatment in OSA patients are two-fold: most importantly via its antioxidant actions melatonin may reduce chemoreflex sensitivity, stabilize ventilatory control and reduce OSA severity; by normalizing sleep phase melatonin may also allow patients to fall asleep easier and wake more refreshed.

Conditions

Obstructive Sleep Apnea

Keywords

loop gain; chemoreflex control; melatonin; antioxidant; obstructive sleep apnea; ventilatory control

Outcome Measures

Primary Outcomes (5)

• change from baseline in hypercapnic and hypoxic ventilatory response tests after one month of melatonin

  modified rebreathing tests will be utilised to assess the entire chemoreflex range

  baseline and after one month of either melatonin or placebo

• change from baseline in apnea hypopnea index after one month of melatonin

  assess using standard sleep scoring criteria

  baseline and after one month of either melatonin or placebo

• change from baseline in loop gain after one month of melatonin

  assessed using flow from standard sleep study with method by Terrill (2014)

  baseline and after one month of either melatonin or placebo

• change from baseline in blood serum oxidative markers after one month of melatonin

  comparison of blood serum Angiotensin II, total glutathione, oxidized/reduced glutathione ratio, glutathione peroxidase, super oxide dismutase, C-Reactive protein, catalase pre and post treatment

  baseline and after one month of either melatonin or placebo

• change from baseline in blood serum melatonin concentration after one week of melatonin

  assessed 2 hourly from 10pm to 6am to determine onset, peak and offset and phase resetting

  baseline and after one week daily 10mg melatonin either 4hrs or 2hrs before bed

Secondary Outcomes (3)

• change from baseline in mean arterial blood pressure after one month of melatonin

  baseline and after one month of either melatonin or placebo

• change from baseline in Epworth Sleepiness Score after one week of melatonin

  baseline and after one week daily 10mg melatonin either 4hrs or 2hrs before bed

• change from baseline in actigraphy watch data and sleep diary entries after one week of melatonin

  one week baseline behaviour and one week of melatonin treatment

Study Arms (4)

Melatonin 4hrs before bed

EXPERIMENTAL

Time of dosage comparison on blood serum melatonin phase and subjective sleepiness

Dietary Supplement: Melatonin

Melatonin 2hrs before bed

EXPERIMENTAL

Time of dosage comparison on blood serum melatonin phase and subjective sleepiness

Dietary Supplement: Melatonin

Melatonin

EXPERIMENTAL

To determine effects of 10mg daily melatonin on chemoreflex control, oxidation status, loop gain and apnea hypopnea index in obstructive sleep apnea

Dietary Supplement: Melatonin

Placebo

PLACEBO COMPARATOR

Placebo outcomes versus melatonin

Other: Placebo

Interventions

Melatonin DIETARY_SUPPLEMENT

Melatonin; Melatonin 2hrs before bed; Melatonin 4hrs before bed

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• Ages 18-70 years
• No other sleep disorders
• Severe OSA (≥30 apnea hypopnea index)

You may not qualify if:

• Females
• Smokers (quit ≥ 1 year ago acceptable)
• Abnormal lung function (FEV1 and FVC \< 80% predicted)
• Any known cardiac (apart from treated hypertension with acceptable drugs, see below), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, hepatic disease, or patients with diabetes.
• History of driving or other accidents due to sleepiness or an ESS \> 18.
• Prior or current use of melatonin.
• Use of serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, ACE inhibitors or any drugs which interfere with the renin-Angiotensin system, Losartan (or other Angiotensin II type 1 receptor antagonists), non-specific calcium channel blockers (L channel specific are acceptable), anti-inflammatories, vitamins or any antioxidants.
• Use of any medications that may affect sleep or breathing.
• A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
• Substantial alcohol (\>3oz/day) or use of illicit drugs.
• More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: June 19, 2015
• First Posted: June 29, 2015
• Study Start: July 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: December 22, 2020

Record last verified: 2020-12

Locations

US (1)