Clinical trial NCT02458469
Conditions: Spinal Cord Injury Sleep Disordered Breathing
Sponsor: VA Office of Research and Development
Start date: 2015-05-14; Completion date: 2019-04-12
Enrollment: 15 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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.

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).

Arms: arm 1: This drug will be taken for two week period arm 2: This drug will be taken for two week period arm 3: A placebo pill will be taken at bed time for two week period
Interventions: intervention 1: Buspirone intervention 2: Trazodone intervention 3: Placebo
Intervention descriptions: intervention 1: 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. intervention 2: 100 mg dose before bed-time intervention 3: One placebo pill before bed-time

Protocol documents:
Prot_SAP_000.pdf: 
 
Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in 
Patients With SCI 
NCT02458469 
 
Abdulghani Sankari, MD, PhD 
3/12/2020 
 
 
 
 


Study Protocol: A pilot randomized placebo-controlled cross-over study. Eligible subjects with 
spinal cord injury were studied on three separate occasions: (1) Buspirone vs. Trazodone vs. 
placebo for 2 weeks; the participants were blinded to what medication they were taking. The 
initial dose of Buspirone is 15 mg daily (7.5 mg b.i.d.). Buspirone dosage was increased 5 mg 
per day at intervals of 2 to 3 days until a maximum dose of 30mg/day is reached. Trazodone 
was given at 100 mg dose before bed-time. 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 hypocapnic apneic threshold followed by two weeks washout. 
(3) Cross over medication for two weeks was followed by another study to determine the 
hypocapnic apneic threshold. For the baseline hypocapnic apneic threshold the nasal 
mechanical ventilation study obtained from specific aim 1 was used as a baseline.  
Statistical Data analysis: The primary endpoint is the CO2 reserve (PETCO2–AT) which is a 
marker to measure susceptibility to hypocapnic central apnea, defined as the difference 
between average end-tidal CO2 (PETCO2) for the control breaths on room air and the breaths 
before the cessation of noninvasive nasal mechanical ventilation. The standard statistical 
package SPSS (Sigmstat, version 3.5) was used for data analysis.  A detailed descriptive 
analysis of all quantitative data was performed involving the summarization of data, and normal 
distribution. The primary analysis was repeated measure analysis of variance. In the absence of 
normal distribution of data, appropriate non-parametric tests were used.