Sleep Disordered Breathing, Spinal Cord Injuries
Conditions
Brief summary
The purpose of this study is to look at the effect of using Mirtazapine 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) and non-injured persons during sleep. During this part of the study participants will be asked to take Mirtazapine (15mg per day) and a placebo in a random fashion, each for a one week period (drug period) of time followed by one week without drugs (washout period). The drugs will not be taken all at the same time, but each will be taken separately for one weeks followed by a night study to look at the effect the Mirtazapine/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 two separate occasions: (1) Mirtazapine vs. placebo for one week; the participants will be blinded to whether they are taking Mirtazapine or placebo. After the one week treatment a sleep study will be repeated. Mirtazapine will be given at 15 mg dose before bed-time. (2) Cross over medication for one week will be followed by a second sleep study.
Interventions
DRUGMirtazapine
15 mg dose before bed-time
DRUGPlacebo
One placebo pill before bed-time
Sponsors
Wayne State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
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 * Non-injured adults
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CO2 Reserve (Delta-PETCO2-AT) | One Week | Randomized placebo-controlled cross-over study. Each subject was studied on two separate occasions: (1) Mirtazapine vs. placebo for one week; After the one-week treatment a physiological sleep study was performed to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold. (2) Cross over medication for one week was followed by a second physiological sleep study to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AHI (Apnea/Hypopnea Index) | One Week | AHI is an index that measures the severity of sleep apnea and is calculated by dividing the total number of apneas and hypopneas by the number of hours of sleep. Randomized placebo-controlled cross-over study. Each subject was studied on two separate occasions: (1) Mirtazapine vs. placebo for one week; After the one-week treatment a polysomnogram (PSG) study was performed to determine the AHI. (2) Cross over medication for one week was followed by a second PSG to determine the AHI. |
Participant flow
Recruitment details
Participants were recruited to the primary site at John D. Dingell VA Medical Center.
Pre-assignment details
Of 150 available, 18 participants were enrolled. Of the 18 enrolled, 15 started the study protocol. Of the 15 that started the study protocol, 10 completed the study and had their results analyzed.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either Mirtazapine (15 mg) or Placebo tablet | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout | Lost to Follow-up | 0 | 1 |
| Washout | Physician Decision | 2 | 0 |
| Washout | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 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 | 1 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 | 8 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 1 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 1 / 12 |
Outcome results
Primary
CO2 Reserve (Delta-PETCO2-AT)
Randomized placebo-controlled cross-over study. Each subject was studied on two separate occasions: (1) Mirtazapine vs. placebo for one week; After the one-week treatment a physiological sleep study was performed to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold. (2) Cross over medication for one week was followed by a second physiological sleep study to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold.
Time frame: One Week
Population: Only 10 of the 15 enrolled participants finished both medication arms (placebo, mirtazapine) and were used in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirtazapine | CO2 Reserve (Delta-PETCO2-AT) | -3.8 mmHg | Standard Deviation 1.2 |
| Placebo | CO2 Reserve (Delta-PETCO2-AT) | -2.0 mmHg | Standard Deviation 1.5 |
p-value: 0.015t-test, 2 sided
Secondary
AHI (Apnea/Hypopnea Index)
AHI is an index that measures the severity of sleep apnea and is calculated by dividing the total number of apneas and hypopneas by the number of hours of sleep. Randomized placebo-controlled cross-over study. Each subject was studied on two separate occasions: (1) Mirtazapine vs. placebo for one week; After the one-week treatment a polysomnogram (PSG) study was performed to determine the AHI. (2) Cross over medication for one week was followed by a second PSG to determine the AHI.
Time frame: One Week
Population: Only 10 of the 15 enrolled participants finished both medication arms (placebo, mirtazapine) and were used in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirtazapine | AHI (Apnea/Hypopnea Index) | 46.4 Events/Hour | Standard Deviation 22.5 |
| Placebo | AHI (Apnea/Hypopnea Index) | 47.8 Events/Hour | Standard Deviation 20.6 |
p-value: 0.82t-test, 2 sided