Sleep Disordered Breathing, Spinal Cord Injury
Conditions
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).
Interventions
DRUGBuspirone
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.
DRUGTrazodone
100 mg dose before bed-time
DRUGPlacebo
One placebo pill before bed-time
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CO2 Reserve (Delta-PETCO2-AT) | Two weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apnea-Hypopnea Index (AHI) | Two weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited to the primary site at John D. Dingell VA Medical Center.
Pre-assignment details
Of 150 available, 15 participants were enrolled. Of the 15 enrolled, 11 started the study protocol.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either Buspirone (7.5-15 mg) or Trazodone (100 mg) or Placebo tablet | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention (2 Weeks) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| First Intervention (2 Weeks) | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention (2 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 10 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 1 / 9 |
Outcome results
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.
Time frame: Two weeks
Population: Only 8 of the 15 enrolled participants finished all three medication arms (placebo, buspirone, trazodone) and were used in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | CO2 Reserve (Delta-PETCO2-AT) | -3.6 mmHg | Standard Deviation 0.9 |
| Trazodone | CO2 Reserve (Delta-PETCO2-AT) | -2.5 mmHg | Standard Deviation 1 |
| Placebo | CO2 Reserve (Delta-PETCO2-AT) | -1.8 mmHg | Standard Deviation 1.5 |
p-value: 0.019ANOVA
p-value: 0.015Student-Newman-Keuls Method
p-value: 0.231Student-Newman-Keuls Method
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.
Time frame: Two weeks
Population: Only 8 of the 15 enrolled participants finished all three medication arms (placebo, buspirone, trazodone) and were used in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Apnea-Hypopnea Index (AHI) | 48.7 Events/Hour | Standard Deviation 21.4 |
| Trazodone | Apnea-Hypopnea Index (AHI) | 40.0 Events/Hour | Standard Deviation 23.9 |
| Placebo | Apnea-Hypopnea Index (AHI) | 45.2 Events/Hour | Standard Deviation 23.2 |
p-value: 0.749ANOVA