Clinical trial NCT02458469: Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI
Official title: Pathogenesis of Sleep Disordered Breathing in Spinal Cord Injury Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injury
Sleep Disordered Breathing
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2015-06-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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).

Eligibility criteria: 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

Primary outcomes:
measure: CO2 Reserve (Delta-PETCO2-AT)
timeFrame: Two weeks
Secondary outcomes:
measure: Apnea-Hypopnea Index (AHI)
timeFrame: Two weeks
Other outcomes:
Locations:
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit, MI
state: Michigan
Study officials:
affiliation: John D. Dingell VA Medical Center, Detroit, MI
name: Abdulghani Sankari, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: