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Trial record 5 of 120 for:    Anti-Bacterial | CYCLOSERINE OR SEROMYCIN

Cycloserine in the Treatment of Sleep Apnea

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ClinicalTrials.gov Identifier: NCT02735694
Recruitment Status : Terminated (Analysis of initial sample shows negative results.)
First Posted : April 13, 2016
Last Update Posted : April 13, 2016
Sponsor:
Collaborator:
University of Calgary
Information provided by (Responsible Party):
University of Manitoba

Brief Summary:
This study is being conducted to determine whether cycloserine is effective for the treatment of sleep apnea. Cycloserine is an antibiotic that has been extensively used in the treatment tuberculosis. However, more recently it was shown to enhance memory responses. Cycloserine may enhance the response of respiratory muscles to apnea and potentially reduce the severity of sleep disordered breathing.

Condition or disease Intervention/treatment Phase
Sleep Apnea Syndromes Drug: Cycloserine Drug: Placebo Phase 1

Detailed Description:

The passive human upper airway (UA) is a collapsible tube with a relatively high compliance. At atmospheric luminal pressure, its cross-sectional area varies considerably. Subjects in whom the pharynx is closed, or nearly closed, at near atmospheric pressure require an upper airway dilating force to maintain adequate ventilation. During wakefulness pharyngeal dilator muscles (dilators) provide the necessary force to permit an adequate flow, regardless of how collapsible the pharynx is. This dilator activity is substantially lost at sleep onset. Subjects in whom the passive UA cannot permit adequate ventilation must recruit dilators through reflex mechanisms if they are to remain asleep. Recent studies have shown that activation of the muscles that open the airway in the course of obstructive apneas persists to a variable degree after the relief of obstruction, evidencing the presence of memory for prior activation in the the brain centers that supply the dilator muscles.

Short-term potentiation (STP) is a neuro-physiological mechanism that results in a time-dependent increase in motor activity, that is not explainable by changes in stimulus intensity, and which persists after disappearance of the stimulus ( "after-discharge"). STP is well documented in diaphragmatic responses to chemical stimuli. Prominent STP in upper airway muscles would promote a stronger dilator response to upper airway occlusion. The after-discharge would also help to maintain dilator activity following the ventilatory phase of obstructive events, thereby mitigating recurrence of obstruction. Patients with obstructive sleep apnea (OSA) vary greatly in the extent to which this memory or STP is present. The investigators postulate that interventions that could potentiate the development of memory for prior activation would mitigate the recurrence of apneas and reduce the severity of obstructive sleep apnea. The same interventions, those that enhance memory for prior activation, would also likely improve central apneas in that these apneas represent loss of diaphragm activity following hyperventilation. Memory for prior activation of the diaphragm has been well documented in the past and appears to be defective in such patients.

There has been extensive research into methods of improving neural memory. Cycloserine, an antibiotic that has been, and continues to be, used extensively in the treatment of drug-resistant tuberculosis, was shown to be effective in promoting memory in small doses (much less than those used for tuberculosis) both in animals and humans. We, therefore, propose that cycloserine has the potential of enhancing the memory properties of neurones supplying pharyngeal muscles and propose to study the effect of using it on the severity of sleep apneas of the obstructive and central varieties.

Patients who have been diagnosed with OSA following routine clinical sleep studies will be asked to participate. Participation involves agreeing to two additional full night studies in the sleep laboratory, separated by 1 week. Both studies will be identical to the routine clinical studies, except that the patient will be asked to swallow a capsule containing either placebo or 250 mg cycloserine 1 to 2 hours prior to going to sleep. The order of the Placebo and Test nights will be randomized. The patient will be monitored continuously by a dedicated, senior polysomnography technologist.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Cycloserine in the Treatment of Sleep Apnea
Study Start Date : September 2015
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Active Comparator: Cycloserine
Cycloserine, 250 mg capsules by mouth, one hour prior to initiation of sleep study, single dose
Drug: Cycloserine
Capsule containing 250 mg of Cycloserine
Other Name: Seromycin

Drug: Placebo
Sugar capsule manufactured to mimic Cycloserine 250 mg capsule
Other Name: Sugar capsule

Placebo Comparator: Placebo
Placebo, sugar capsule by mouth, one hour prior to initiation of sleep study, single dose
Drug: Cycloserine
Capsule containing 250 mg of Cycloserine
Other Name: Seromycin

Drug: Placebo
Sugar capsule manufactured to mimic Cycloserine 250 mg capsule
Other Name: Sugar capsule




Primary Outcome Measures :
  1. Change in Apnea-hypopnea index (AHI) [ Time Frame: Baseline and one week ]
    Baseline apnea-hypopnea index in first night and upon end of the second sleep study, performed one week apart


Secondary Outcome Measures :
  1. Improvement in total sleep time [ Time Frame: Baseline and one week ]
  2. Improvement in average oxygen saturation [ Time Frame: One week ]

Other Outcome Measures:
  1. Improvement in the awakening and arousals index [ Time Frame: One week ]
    number of awakenings and arousals per hour of sleep as measurement of sleep continuity.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Moderate to severe obstructive or central sleep apnea (Apnea Hypopnea Index > 30/hr).
  • Minimum Oxygen saturation during respiratory events >70% throughout sleep during the clinical sleep study.

Exclusion Criteria:

  • Contraindication to the use of cycloserine, namely history of allergy to cycloserine, seizures, depression, severe anxiety or psychosis, excessive use of alcohol or renal failure.
  • Past or current history of tuberculosis
  • Hypercapnia > 55 millimeters of mercury during the diagnostic clinical sleep study.
  • Neuromuscular disease.
  • Obesity-hypoventilation syndrome.
  • Pregnancy.
  • Significant co-morbidities: Dialysis-dependant renal failure, severe asthma or chronic lung disease, congestive heart failure, previous stroke.
  • Recent (within 3 months) myocardial infarction or Active coronary ischemia event.

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): NCT02735694


Locations
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Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4N1
Canada, Manitoba
Sleep Disorders Centre
Winnipeg, Manitoba, Canada, R3C 1A2
Sponsors and Collaborators
University of Manitoba
University of Calgary
Investigators
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Principal Investigator: Magdy K Younes, Md, PhD University of Manitoba

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Responsible Party: University of Manitoba
ClinicalTrials.gov Identifier: NCT02735694     History of Changes
Other Study ID Numbers: B2013:044
MA-7954 ( Other Grant/Funding Number: CIHR )
9427-U0304-36C ( Other Identifier: Health Canada )
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: April 13, 2016
Last Verified: November 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan has been made on sharing individual data

Keywords provided by University of Manitoba:
Sleep apnea
Hypoglossal Nerve
N-methyl-D-aspartate receptors
Cycloserine
Short-term potentiation

Additional relevant MeSH terms:
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Cycloserine
Antibiotics, Antitubercular
Anti-Bacterial Agents
Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action