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

February 16, 2016 updated by: VA Office of Research and Development

Buspirone as a Potential Treatment for Recurrent Central Apneas

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.

Study Overview

Status

Terminated

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

Interventional

Enrollment (Actual)

8

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Cleveland, Ohio, United States, 44106
        • VA Medical Center, Cleveland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kingman P. Strohl, MD, VA Medical Center, Cleveland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

September 2, 2008

First Submitted That Met QC Criteria

September 3, 2008

First Posted (Estimate)

September 4, 2008

Study Record Updates

Last Update Posted (Estimate)

March 14, 2016

Last Update Submitted That Met QC Criteria

February 16, 2016

Last Verified

February 1, 2016

More Information

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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