Baclofen and Hypoxia-induced Periodic Ventilation - Full Text View

Purpose

Periodic ventilation that includes CHEYNE Stokes ventilation is a pathological pattern characterized by alternating periods of hyperpneas and apnea-hypopneas. It occurs generally during sleep, at high altitude and in hypoxic conditions in healthy subjects, and in some diseases like congestive heart failure. One study conducted on an animal model suggested that baclofen, a drug already used against spasticity in humans, could also be effective against periodic ventilation. The goal of the study is therefore to assess this hypothesis on hypoxia-induced periodic ventilation in healthy subjects during sleep.

Condition	Intervention	Phase
CHEYNE Stokes Respiration	Drug: Baclofen Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Assessment of the Effect of the GABA-B Receptor Agonist, Baclofen, on Hypoxia-induced Periodic Ventilation, in Healthy Subjects

Resource links provided by NLM:

Drug Information available for: Baclofen

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Decrease in the coefficient of variation of the period of the ventilatory cycle [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
The primary outcome will be the decrease in the coefficient of variation of the period of the ventilatory cycle. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.

Secondary Outcome Measures:

Decrease in the coefficient of variation of the tidal volume [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Decrease in the coefficient of variation of the tidal volume. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Decrease in the coefficient of variation of the end tidal CO2 pressure [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Decrease in the coefficient of variation of the end tidal CO2 pressure. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Decrease in the number of frequency compounds of the ventilatory flow [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Decrease in the number of frequency compounds of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Decrease in the apnea-hypopnea index [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Decrease in the apnea-hypopnea index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Decrease in the sleep fragmentation index [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Decrease in the sleep fragmentation index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Change in the non-linea dynamics of the ventilatory flow [ Time Frame: During the second and the third session in hypoxia ] [ Designated as safety issue: No ]
Change in the non-linea dynamics of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.

Enrollment:	53
Study Start Date:	March 2010
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Baclofen	Drug: Baclofen Breaking tablets of 10 mg of baclofen. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. Other Name: Baclofen
Placebo Comparator: Placebo Placebo	Drug: Placebo Breaking tablets of 10 mg of placebo. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. Other Name: Placebo

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Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Adult
Male
Body mass index between 20 and 30 kg/m2
Healthy (no known disease)
No regular treatment except first grade antalgic drugs (e. g. ACETAMINOFEN)
Written consent to participate in the study
Health insurance

Exclusion Criteria:

Intolerance to baclofen
Tobacco, alcohol or drug consumption
Past history of possible acute mountain sickness
Regular treatment for any disease
Claustrophobia
Coronary disease
Hypertension
Cardiac failure
Cardiac rhythm abnormalities
Pulmonary hypertension
Any pulmonary artery abnormality
Any cardiac disease
Past history of cerebral ischemia
Past history of psychiatric disorder
Any respiratory disease (including asthma)
Leg arteriopathy
Sickle cell anemia
Renal insufficiency
Migraine
Diabetes
Obesity
Thalassemia
Scoliosis
Past history of phlebitis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01095679

Locations

France
Pitié-Salpêtrière Hospital
Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Christian Straus, MD, PhD

Assistance Publique - Hôpitaux de Paris

More Information

No publications provided

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01095679 History of Changes
Other Study ID Numbers:	P090207
Study First Received:	March 29, 2010
Last Updated:	October 30, 2012
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

CHEYNE Stokes respiration
Periodic ventilation
baclofen
hypoxia
healthy subject

Additional relevant MeSH terms:

Cheyne-Stokes Respiration
Anoxia
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Baclofen
GABA-B Receptor Agonists
GABA Agonists
GABA Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Muscle Relaxants, Central
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Baclofen and Hypoxia-induced Periodic Ventilation (PERIODIBAC)