Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI

Study Overview
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Brief Summary
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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
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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).

Official Title
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Pathogenesis of Sleep Disordered Breathing in Spinal Cord Injury Patients

Conditions
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Spinal Cord Injury, Sleep Disordered Breathing

Intervention / Treatment
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* Drug: Buspirone
* Drug: Trazodone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Buspirone<br>This drug will be taken for two week period | Drug: Buspirone<br>* 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.<br>|
| Active Comparator: Trazodone<br>This drug will be taken for two week period | Drug: Trazodone<br>* 100 mg dose before bed-time<br>|
| Placebo Comparator: Placebo<br>A placebo pill will be taken at bed time for two week period | Drug: Placebo<br>* One placebo pill before bed-time<br>|

What is the study measuring?
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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 |