Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI (REST-SCI)

Pathogenesis of Sleep Disordered Breathing in Spinal Cord Injury Patients

The purpose of this study is to look at the effect of exciting using drugs to target a specific pathway in the body, that relies on a natural chemical the body produces called 'serotonin', in patients with spinal cord injury (SCI) during sleep. During this part of the study participants will be asked to take buspirone (Buspar) (15-50mg per day), trazodone (100mg per day) and a placebo in a random fashion, each for a 2 week period (drug period) of time followed by two weeks without drugs (washout period). The drugs will not be taken all at the same time, but each will be taken separately for two weeks followed by a night study to look at the effect the medication/placebo pill has on the way the body responds during sleep.

Study Overview

• Status: Completed
• Conditions: Sleep Disordered Breathing; Spinal Cord Injury
• Intervention / Treatment: Drug: Placebo; Drug: Buspirone; Drug: Trazodone

Detailed Description

Randomized placebo controlled cross-over study. Each subject will be studied on three separate occasions: (1) Buspirone vs. Trazodone vs. placebo for 2 weeks; the patients will be blinded to whether they are taking trazodone or placebo; buspirone cannot be blinded because it is dosed twice a day and is up titrated during the two weeks of administration. The initial dose of Buspirone is 15 mg daily (7.5 mg bid.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day until a maximum dose 30mg/day is reached. After the two week treatment a sleep study will be repeated. Trazodone will be given at 100 mg dose before bed-time. (2) Cross over medication for two weeks will be followed by a second sleep study followed by two weeks washout. (3) Cross over medication for two weeks will be followed by another sleep study. To assess the clinical effect of the drug on breathing during sleep a qualitative polysomnography will be performed for 2 hours the same night after taking the drug/placebo. This will allow the determination of ventilatory changes and the determination of the number of respiratory events (apnea/hypopnea index).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • John D. Dingell VA Medical Center, Detroit, MI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults with SCI (>6months after spinal cord injury) at the T6 level/above

Exclusion Criteria:

• Pregnant and lactating females
• Heart failure, vascular disease, or stroke
• Advanced chronic obstructive pulmonary disease (COPD), liver disease, and chronic kidney disease
• BMI >38 kg/m2
• Mechanical ventilation dependence

• The following medications are not allowed (potential interaction with buspirone or inhibition of the CYP3A4 system):

  • cimetidine
  • ketoconazole
  • ritonavir
  • itraconazole
  • erythromycin
  • diltiazem
  • verapamil
  • Monoamine oxidase (MAO) inhibitors [such as Marplan, Nardil, Parmate, Emsam]
  • Other prohibited concomitant medications include haloperidol, trazodone, or triazolam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Buspirone; This drug will be taken for two week period	Drug: Buspirone; The initial dose of Buspirone is 15 mg daily (7.5 mg bid.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day until a maximum dose 30mg/day is reached.
Active Comparator: Trazodone; This drug will be taken for two week period	Drug: Trazodone; 100 mg dose before bed-time
Placebo Comparator: Placebo; A placebo pill will be taken at bed time for two week period	Drug: Placebo; One placebo pill before bed-time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CO2 Reserve (Delta-PETCO2-AT)	Randomized placebo-controlled cross-over study. Each subject was studied on three separate occasions: (1) Buspirone vs. Trazodone vs. placebo for 2 weeks; After the two-week treatment a noninvasive nasal mechanical ventilation study was repeated to determine the hypocapnic apneic threshold. (2) Cross over medication for two weeks was followed by a second noninvasive nasal mechanical ventilation study to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold followed by two weeks washout. (3) Cross over medication for two weeks was followed by another sleep study to determine the hypocapnic apneic threshold.	Two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea-Hypopnea Index (AHI)	Randomized placebo-controlled cross-over study. Each subject was studied on three separate occasions: (1) Buspirone vs. Trazodone vs. placebo for 2 weeks; After the two-week treatment a polysomnogram (PSG) study was repeated to determine the AHI. (2) Cross over medication for two weeks was followed by a second PSG to determine the AHI followed by two weeks washout. (3) Cross over medication for two weeks was followed by another sleep study to determine the AHI.	Two weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2015
• Primary Completion (Actual): April 12, 2019
• Study Completion (Actual): April 12, 2019

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Sleep Apnea Syndromes; Respiratory Aspiration; Spinal Cord Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Buspirone; Trazodone
• Other Study ID Numbers: NURC-062-12S; 1IK2CX000547 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No