- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00746954
Buspirone as a Potential Treatment for Recurrent Central Apnea (CSA treatment)
Buspirone as a Potential Treatment for Recurrent Central Apneas
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The hypothesis is that buspirone is a safe, effective drug to reduce the occurrence of recurrent central apnea and irregular breathing found in the setting of heart failure. A secondary hypothesis is that its effect will be similar to that or acetazolamide. Study Design: A one-dose double-blind crossover study of buspirone vs. placebo vs. acetazolamide will be performed to determine if active drug alters the number and/or severity of recurrent central apneas and hypopneas (AHI) in patients with heart failure. AHI is the primary outcome variable. In the initial phase of this study, we will recruit 18-20 patients to obtain ~15 complete studies, using the assumption of a ~20% drop-out, to reach a pre-set significance level of a 30% reduction in AHI in the drug groups with a power of 0.90 and a p=0.05 by post-hoc testing. Power estimates were calculated using the means and SDs derived from the population reported the study of acetazolamide by Javaheri et al (2006). A 30% reduction in AHI would be meaningful. A 15% dropout rate was present in the study by Javaheri et al (2006), but as our study is a three-way comparison, we chose a slightly higher rate. The reasons stated in these articles for a drop out included: viral illness, GI upset (on placebo or on theophyllin), tired of the sleep studies, and desire to terminate without cause. Statistical Analyses. Analysis of variance for repeated measures using Sidak's correction will be used to compare placebo, buspirone, and acetazolamide studies. For variables that are not normally distributed, Dunn's nonparametric test for multiple comparisons will be used. p > 0.05 will be considered significant. Mean values and SDs will be reported. This single dose, one night study is called Buspirone as a Potential Treatment for Recurrent Sleep Apnea I.
The randomization will be in a block design, and the analysis will take into account the blocked design. We will recruit 30 patients to obtain ~27 complete studies, using the assumption of a ~25% drop-out, to reach a pre-set significance level of a 50% reduction in AHI in the drug groups with a power of 0.90 and a p=0.05 by post-hoc testing (see Table C below). Power estimates were calculated using the means and SDs derived from the population reported the study of a one week trial of acetazolamide by Javaheri, values similar to those in the drug trial for theophyllin. Our reasoning is that a 50% reduction in AHI would be most meaningful. Our drop-out rate in the one-night study is estimated at ~25%.
Exclusion criteria of use of selective serotonin reuptake inhibitors (SSRIs) or antidepressants, while necessary because one of the drugs was buspirone, were too stringent for completion of this study in the VA setting. Of ~1000 patient charts screens, 8 were eventually entered into the trial, so that power criteria were not met. Records are being utilized to probe for hidden features in the PSG for use in future drug trials.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Ohio
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Cleveland, Ohio, United States, 44106
- VA Medical Center, Cleveland
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Ability to provide informed consent,
- Ambulatory and in stable condition for the past 4 months,
- A diagnosis of heart failure with left ventricular systolic dysfunction as evidenced by an ejection fraction <35%,
- NYHA class II or III clinical status, and
- Diagnosis of dilated cardiomyopathy or ischemic cardiomyopathy.
Exclusion Criteria:
- Unstable angina, unstable heart failure, acute pulmonary edema, congenital heart disease
- History of unstable and/or advanced hepatic disease
- History of renal failure, CrCL < 30
- Current use of an SSRI, or use within one month of testing
- Intrinsic pulmonary diseases: ILD and/or COPD (FEV1/FVC < 65%)
- Kyphoscoliosis or neuromuscular disease
- Suboptimally treated hypothyroidism
- Use of narcotics or benzodiazepines
- Use of theophylline or pseudoephedrine
Use the following medications:
- MAO inhibitors
- diazepam
- haloperidol
- nefazodone
- trazodone
- erythromycin
- grapefruit juice
- itraconazole
- rifampin
- ketoconazole
- ritonavir,
- cimetidine
- Known allergy to buspirone or acetazolamide
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Arm 1 BUS to PLA to ACET
Each patient will act as their own control, with comparisons over three nights, each night given buspirone (BUS 20mg), actetazolamide (ACET 250mg), or placebo (PLA) n=3
|
Cabonic Anhydrase inhibitor
Agonist of a 5-HT1a receptor with some D2 agonist properties.
|
Other: ARM 2 ACET to BUS to PLA
Each patient will act as their own control, with comparisons over three nights, each night given buspirone (BUS 20mg), actetazolamide (ACET 250mg), or placebo (PLA) n=3
|
Cabonic Anhydrase inhibitor
Agonist of a 5-HT1a receptor with some D2 agonist properties.
|
Other: ARM 3 PLA to ACET to BUS
Each patient will act as their own control, with comparisons over three nights, each night given buspirone (BUS 20mg), actetazolamide (ACET 250mg), or placebo (PLA) n=2
|
Cabonic Anhydrase inhibitor
Agonist of a 5-HT1a receptor with some D2 agonist properties.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Apnea-hypopnea Index (Number of Central and Mixed Apneas/Hour of Sleep)
Time Frame: Overnight polysomnogram over 3 separate nights
|
Overnight polysomnogram over 3 separate nights
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Kingman P. Strohl, MD, VA Medical Center, Cleveland
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Respiratory Tract Diseases
- Respiration Disorders
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Signs and Symptoms, Respiratory
- Sleep Apnea Syndromes
- Apnea
- Sleep Apnea, Central
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Carbonic Anhydrase Inhibitors
- Natriuretic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Receptor Agonists
- Anti-Anxiety Agents
- Diuretics
- Anticonvulsants
- Buspirone
- Acetazolamide
Other Study ID Numbers
- RESP-006-07F
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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