Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02484300
Recruitment Status : Recruiting
First Posted : June 29, 2015
Last Update Posted : January 15, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Robert L. Owens, University of California, San Diego

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.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Dietary Supplement: Melatonin Other: Placebo Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Melatonin on Sleep and Ventilatory Control in Obstructive Sleep Apnea
Actual Study Start Date : July 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea
Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: Melatonin 4hrs before bed
Time of dosage comparison on blood serum melatonin phase and subjective sleepiness
Dietary Supplement: Melatonin
Experimental: Melatonin 2hrs before bed
Time of dosage comparison on blood serum melatonin phase and subjective sleepiness
Dietary Supplement: Melatonin
Experimental: Melatonin
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 Comparator: Placebo
Placebo outcomes versus melatonin
Other: Placebo



Primary Outcome Measures :
  1. change from baseline in hypercapnic and hypoxic ventilatory response tests after one month of melatonin [ Time Frame: baseline and after one month of either melatonin or placebo ]
    modified rebreathing tests will be utilised to assess the entire chemoreflex range

  2. change from baseline in apnea hypopnea index after one month of melatonin [ Time Frame: baseline and after one month of either melatonin or placebo ]
    assess using standard sleep scoring criteria

  3. change from baseline in loop gain after one month of melatonin [ Time Frame: baseline and after one month of either melatonin or placebo ]
    assessed using flow from standard sleep study with method by Terrill (2014)

  4. change from baseline in blood serum oxidative markers after one month of melatonin [ Time Frame: baseline and after one month of either melatonin or placebo ]
    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

  5. change from baseline in blood serum melatonin concentration after one week of melatonin [ Time Frame: baseline and after one week daily 10mg melatonin either 4hrs or 2hrs before bed ]
    assessed 2 hourly from 10pm to 6am to determine onset, peak and offset and phase resetting


Secondary Outcome Measures :
  1. change from baseline in mean arterial blood pressure after one month of melatonin [ Time Frame: baseline and after one month of either melatonin or placebo ]
  2. change from baseline in Epworth Sleepiness Score after one week of melatonin [ Time Frame: baseline and after one week daily 10mg melatonin either 4hrs or 2hrs before bed ]
    To compare subjective daytime sleepiness following 1 week melatonin use versus baseline

  3. change from baseline in actigraphy watch data and sleep diary entries after one week of melatonin [ Time Frame: one week baseline behaviour and one week of melatonin treatment ]
    To compare potential changes in sleep patterns and activity at home



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02484300


Locations
Layout table for location information
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92093
Contact: Robert Owens, MD       rowens@ucsd.edu   
Principal Investigator: Robert Owens, MD         
Sponsors and Collaborators
University of California, San Diego
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)

Layout table for additonal information
Responsible Party: Robert L. Owens, Assistant Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02484300     History of Changes
Other Study ID Numbers: 150465
R01HL085188 ( U.S. NIH Grant/Contract )
First Posted: June 29, 2015    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019
Keywords provided by Robert L. Owens, University of California, San Diego:
loop gain
chemoreflex control
melatonin
antioxidant
obstructive sleep apnea
ventilatory control
Additional relevant MeSH terms:
Layout table for MeSH terms
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Dyssomnias
Nervous System Diseases
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants