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

Spinal Cord Injury Clinical Trial

— REST-SCI  

Official title:

Pathogenesis of Sleep Disordered Breathing in Spinal Cord Injury Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02458469
• Other study ID #: NURC-062-12S
• Secondary ID: 1IK2CX000547
• Status: Completed
• Phase: Phase 2
• Start date: May 14, 2015
• Est. completion date: April 12, 2019

Study information

• Verified date: June 2021
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 12, 2019
• Est. primary completion date: April 12, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Respiratory Aspiration
• Sleep Apnea Syndromes
• Sleep Disordered Breathing
• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

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.
• Trazodone
100 mg dose before bed-time
• Placebo
One placebo pill before bed-time

Locations

Country	Name	City	State
United States	John D. Dingell VA Medical Center, Detroit, MI	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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