Trial Outcomes & Findings for Abnormal Ventilatory Response to Carbon Dioxide: a Potential Biomarker for Seizure Induced Respiratory Depression & Modification by SSRI (NCT NCT02929667)
NCT ID: NCT02929667
Last Updated: 2020-05-04
Results Overview
Number of participants enrolled every 3 months.
COMPLETED
PHASE2
30 participants
From the date of enrollment every 3 months up to 2 years
2020-05-04
Participant Flow
A total of 30 subjects enrolled from February 2017 to February 2019. These 30 subjects underwent further screening before randomization to an intervention. Eight of the subjects failed to meet eligibility for randomization to an intervention, hence only 22 participants were randomized equally (1:1) to one of the treatment arms.
A total of 6 subjects with HCVR slope of \> 2.0 L/min/mm Hg were excluded.Two additional subjects did not meet other inclusion criteria for randomization.
Participant milestones
| Measure |
Treatment
Subjects randomized to treatment arm will receive fluoxetine with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Fluoxetine: Standard 6 weeks titration, starting 10 mg per day.
|
Control
Subjects randomized to control arm will receive placebo with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Placebo: Standard 6 weeks titration.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Abnormal Ventilatory Response to Carbon Dioxide: a Potential Biomarker for Seizure Induced Respiratory Depression & Modification by SSRI
Baseline characteristics by cohort
| Measure |
Treatment
n=11 Participants
Subjects randomized to treatment arm will receive fluoxetine with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Fluoxetine: Standard 6 weeks titration, starting 10 mg per day.
|
Control
n=11 Participants
Subjects randomized to control arm will receive placebo with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Placebo: Standard 6 weeks titration.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the date of enrollment every 3 months up to 2 yearsPopulation: Due to being a feasibility study, recruitment is reported for the whole population (drug + placebo).
Number of participants enrolled every 3 months.
Outcome measures
| Measure |
Recruitment
n=30 Participants
Number of subjects (both fluoxetine and placebo arms) enrolled in the study.
|
Placebo
Subjects randomized to receive placebo.
|
|---|---|---|
|
Study Recruitment Rate
|
3.8 participants/3 months
Interval 0.0 to 6.0
|
—
|
PRIMARY outcome
Timeframe: From date of enrollment until either completion of study or lost to follow up every 3 months up to 2 years and 3 monthsNumber of participants completing the study every 3 months.
Outcome measures
| Measure |
Recruitment
n=11 Participants
Number of subjects (both fluoxetine and placebo arms) enrolled in the study.
|
Placebo
n=11 Participants
Subjects randomized to receive placebo.
|
|---|---|---|
|
Study Retention Rate
|
1.2 participants/3 months
Interval 0.0 to 4.0
|
1.1 participants/3 months
Interval 0.0 to 3.0
|
SECONDARY outcome
Timeframe: At the end of HCVR testing- at baseline and 4 weeks after receiving an interventionPopulation: Minute ventilation at the end of HCVR- 4 weeks after receiving an intervention was compared to minute ventilation during baseline HCVR testing in each group.
Minute ventilation was evaluated at baseline HCVR testing and HCVR testing at 4 weeks after receiving an intervention. Change from baseline was calculated.
Outcome measures
| Measure |
Recruitment
n=11 Participants
Number of subjects (both fluoxetine and placebo arms) enrolled in the study.
|
Placebo
n=11 Participants
Subjects randomized to receive placebo.
|
|---|---|---|
|
Change in Minute Ventilation During Hypercapnic Ventilatory Response (HCVR) Testing
|
1.739 Liters/minute (L/min)
Interval -2.991 to 6.469
|
2.758 Liters/minute (L/min)
Interval -2.955 to 8.47
|
SECONDARY outcome
Timeframe: At baseline and 4 weeks after randomization to an interventionPopulation: PHQ-9 scores 4 weeks of receiving an intervention is compared to the baseline scores in each group.
Patient Health Questionnaire (PHQ-9) was used to evaluate mood. Score on PHQ-9 scale ranges from 0-27. Scores corresponding to severity of depression: 0-4: minimal to none ; 5-9: mild; 10-14: moderate; 15-19 moderately severe; 20-27: severe. All subjects in the study were interviewed using standard questions per PHQ-09 questionnaire at baseline and 4 weeks after randomization to an intervention.
Outcome measures
| Measure |
Recruitment
n=11 Participants
Number of subjects (both fluoxetine and placebo arms) enrolled in the study.
|
Placebo
n=11 Participants
Subjects randomized to receive placebo.
|
|---|---|---|
|
Change in PHQ-9 Score.
|
0.455 score on a scale
Interval -4.309 to 5.218
|
-1.000 score on a scale
Interval -4.194 to 2.194
|
SECONDARY outcome
Timeframe: At baseline and 4 weeks after receiving an interventionPopulation: During CO2 rebreathing (HCVR) testing, CO2 gradually rise in the body that stimulates breathing, which in turn increases minute ventilation (L/min). The rate of this increase in minute ventilation with each mm Hg rise in CO2 is the HCVR slope, hence expressed as L/min/mm Hg unit.
All the subjects undergo CO2 rebreathing (HCVR) testing at baseline and 4 weeks after receiving an intervention. During CO2 rebreathing (HCVR) testing, CO2 gradually rise in the body that stimulates breathing, which in turn increases minute ventilation (L/min). The rate of this increase in minute ventilation with each mm Hg rise in CO2 is the HCVR slope, which is calculated for baseline testing and 4 weeks after receiving an intervention. HCVR slope at 4 weeks after receiving an intervention compared to the baseline HCVR slope in each group.
Outcome measures
| Measure |
Recruitment
n=11 Participants
Number of subjects (both fluoxetine and placebo arms) enrolled in the study.
|
Placebo
n=11 Participants
Subjects randomized to receive placebo.
|
|---|---|---|
|
Change in Slope of HCVR
|
-0.049 Liters/minute/mm Hg (L/min/mm Hg)
Interval -0.511 to 0.412
|
0.072 Liters/minute/mm Hg (L/min/mm Hg)
Interval -0.686 to 0.83
|
Adverse Events
Fluoxetine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Fluoxetine
n=11 participants at risk
Subjects randomized to treatment arm will receive fluoxetine with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Fluoxetine: Standard 6 weeks titration, starting 10 mg per day.
|
Placebo
n=11 participants at risk
Subjects randomized to control arm will receive placebo with titration schedule consisting of 10 mg per day for 1 week, 20 mg per day for 1 week, 40 mg per day for 2 weeks, 20 mg per day for 1 week and 10 mg per day for 1 week. Then stop.
Placebo: Standard 6 weeks titration.
|
|---|---|---|
|
Nervous system disorders
Moderate, probably related
|
9.1%
1/11 • Number of events 1 • Adverse events were monitored and collected after randomization up to 7 weeks from study drug initiation or study dropout which ever was closer.
We used definition of adverse events similar to clinicaltrials.gov.
|
0.00%
0/11 • Adverse events were monitored and collected after randomization up to 7 weeks from study drug initiation or study dropout which ever was closer.
We used definition of adverse events similar to clinicaltrials.gov.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place