Buspirone as a Potential Treatment for Recurrent Central Apnea (CSA treatment)

This study has been terminated.
(Patient recruitment and Funding inadequate to finish trial)
Sponsor:
Collaborator:
University Hospital Case Medical Center
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00746954
First received: September 2, 2008
Last updated: February 16, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to determine whether buspirone compared to acetazolamide and to placebo will reduce the number and/or severity of breathing pauses during sleep that occur in some patients with Heart Failure.

Condition Intervention Phase
Central Apnea
Heart Failure
Drug: Acetazolamide
Drug: Buspirone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Buspirone as a Potential Treatment for Recurrent Central Apneas

Resource links provided by NLM:


Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:
  • Apnea-hypopnea Index (Number of Central and Mixed Apneas/Hour of Sleep) [ Time Frame: Overnight polysomnogram over 3 separate nights ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: September 2008
Study Completion Date: December 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Acetazolamide
Cabonic Anhydrase inhibitor
Drug: Buspirone
Agonist of a 5-HT1a receptor with some D2 agonist properties.
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
Drug: Acetazolamide
Cabonic Anhydrase inhibitor
Drug: Buspirone
Agonist of a 5-HT1a receptor with some D2 agonist properties.
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
Drug: Acetazolamide
Cabonic Anhydrase inhibitor
Drug: Buspirone
Agonist of a 5-HT1a receptor with some D2 agonist properties.

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.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00746954

Locations
United States, Ohio
VA Medical Center, Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
VA Office of Research and Development
University Hospital Case Medical Center
Investigators
Principal Investigator: Kingman P. Strohl, MD VA Medical Center, Cleveland
  More Information

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00746954     History of Changes
Other Study ID Numbers: RESP-006-07F 
Study First Received: September 2, 2008
Results First Received: November 5, 2013
Last Updated: February 16, 2016
Health Authority: United States: Federal Government

Keywords provided by VA Office of Research and Development:
buspirone
acetazolamide

Additional relevant MeSH terms:
Heart Failure
Apnea
Sleep Apnea, Central
Heart Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Apnea Syndromes
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Buspirone
Acetazolamide
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Diuretics
Natriuretic Agents

ClinicalTrials.gov processed this record on July 28, 2016