Trial Outcomes & Findings for Improving Buprenorphine Detoxification Outcomes With Isradipine (NCT NCT01895270)
NCT ID: NCT01895270
Last Updated: 2017-06-05
Results Overview
Illicit results via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the taper
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
28 participants
Primary outcome timeframe
thrice weekly for approx 2 weeks (taper)
Results posted on
2017-06-05
Participant Flow
96 consented to screen under a separate screening protocol. Of these, 28 signed consent for this clinical trial. Of 28 signing informed consent, 3 signed informed consent but did not start the trial: one was assigned to ISR and one to PLA. One was lost to follow up before they could be cleared for study entry
Participant milestones
| Measure |
Isradipine
Isradipine controlled-release formulation, 10 mg/day maintenance dose, will be administered according to the following dose procedures: Isradipine ingestion will occur under supervision 6 days per week, and a take-home dose will be given on Saturday for participants to take on Sunday. The initial dose of isradipine or placebo will be given on Day 3 of Week 1. The initial dose of isradipine will be 5 mg/day; the dose will increase to 10 mg/day on Day 3 of Week 3 and will continue through Day 2 of Week 7. On Day 3 of Week 7, isradipine will be decreased to 5 mg/day for 7 days. On Days 3-5 of Week 8, all participants will receive placebo. If ISR side effects are too severe at the 10-mg dose, isradipine will be decreased to 5 mg/day. If ISR side effects are too severe at 5 mg/day, isradipine will be discontinued and the participant will be discharged from the study and referred to local treatment agencies.
Isradipine: Isradipine extended release formulation
|
Placebo
Placebo will consist of microcrystalline cellulose. Two placebo capsules will be administered per day starting week 1 day 3 through the end of the isradipine taper.
Placebo: Placebo will consist of microcrystalline cellulose.
|
|---|---|---|
|
Study Medications Induction (W1-4)
STARTED
|
11
|
14
|
|
Study Medications Induction (W1-4)
COMPLETED
|
5
|
8
|
|
Study Medications Induction (W1-4)
NOT COMPLETED
|
6
|
6
|
|
Buprenorphine Taper (W5 to W6D3)
STARTED
|
5
|
7
|
|
Buprenorphine Taper (W5 to W6D3)
COMPLETED
|
2
|
2
|
|
Buprenorphine Taper (W5 to W6D3)
NOT COMPLETED
|
3
|
5
|
|
Isradipine Taper (W7-8)
STARTED
|
2
|
2
|
|
Isradipine Taper (W7-8)
COMPLETED
|
2
|
0
|
|
Isradipine Taper (W7-8)
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Isradipine
Isradipine controlled-release formulation, 10 mg/day maintenance dose, will be administered according to the following dose procedures: Isradipine ingestion will occur under supervision 6 days per week, and a take-home dose will be given on Saturday for participants to take on Sunday. The initial dose of isradipine or placebo will be given on Day 3 of Week 1. The initial dose of isradipine will be 5 mg/day; the dose will increase to 10 mg/day on Day 3 of Week 3 and will continue through Day 2 of Week 7. On Day 3 of Week 7, isradipine will be decreased to 5 mg/day for 7 days. On Days 3-5 of Week 8, all participants will receive placebo. If ISR side effects are too severe at the 10-mg dose, isradipine will be decreased to 5 mg/day. If ISR side effects are too severe at 5 mg/day, isradipine will be discontinued and the participant will be discharged from the study and referred to local treatment agencies.
Isradipine: Isradipine extended release formulation
|
Placebo
Placebo will consist of microcrystalline cellulose. Two placebo capsules will be administered per day starting week 1 day 3 through the end of the isradipine taper.
Placebo: Placebo will consist of microcrystalline cellulose.
|
|---|---|---|
|
Study Medications Induction (W1-4)
Withdrawal by Subject
|
0
|
2
|
|
Study Medications Induction (W1-4)
Vitals outside of ISR dosing parameters
|
3
|
2
|
|
Study Medications Induction (W1-4)
noncompliance- missed medications
|
3
|
1
|
|
Study Medications Induction (W1-4)
Blood pressure issues
|
0
|
1
|
|
Buprenorphine Taper (W5 to W6D3)
noncompliance - missed medication
|
3
|
5
|
|
Isradipine Taper (W7-8)
Lost to Follow-up
|
0
|
1
|
|
Isradipine Taper (W7-8)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Improving Buprenorphine Detoxification Outcomes With Isradipine
Baseline characteristics by cohort
| Measure |
Isradipine
n=11 Participants
Isradipine controlled-release formulation, 10 mg/day maintenance dose, will be administered according to the following dose procedures: Isradipine ingestion will occur under supervision 6 days per week, and a take-home dose will be given on Saturday for participants to take on Sunday. The initial dose of isradipine or placebo will be given on Day 3 of Week 1. The initial dose of isradipine will be 5 mg/day; the dose will increase to 10 mg/day on Day 3 of Week 3 and will continue through Day 2 of Week 7. On Day 3 of Week 7, isradipine will be decreased to 5 mg/day for 7 days. On Days 3-5 of Week 8, all participants will receive placebo. If ISR side effects are too severe at the 10-mg dose, isradipine will be decreased to 5 mg/day. If ISR side effects are too severe at 5 mg/day, isradipine will be discontinued and the participant will be discharged from the study and referred to local treatment agencies.
Isradipine: Isradipine extended release formulation
|
Placebo
n=14 Participants
Placebo will consist of microcrystalline cellulose. Two placebo capsules will be administered per day starting week 1 day 3 through the end of the isradipine taper.
Placebo: Placebo will consist of microcrystalline cellulose.
|
Total
n=25 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
|
14 Participants
n=7 Participants
|
25 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
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
24 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
|
14 participants
n=7 Participants
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: thrice weekly for approx 2 weeks (taper)Population: Urine data of subjects that received at least one dose of isradipine and returned for at least one visit in which a urine drug screen was obtained were included in the analysis
Illicit results via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the taper
Outcome measures
| Measure |
Isradipine
n=7 Urine drug screen results
Isradipine controlled-release formulation, 10 mg/day maintenance dose, will be administered according to the following dose procedures: Isradipine ingestion will occur under supervision 6 days per week, and a take-home dose will be given on Saturday for participants to take on Sunday. The initial dose of isradipine or placebo will be given on Day 3 of Week 1. The initial dose of isradipine will be 5 mg/day; the dose will increase to 10 mg/day on Day 3 of Week 3 and will continue through Day 2 of Week 7. On Day 3 of Week 7, isradipine will be decreased to 5 mg/day for 7 days. On Days 3-5 of Week 8, all participants will receive placebo. If ISR side effects are too severe at the 10-mg dose, isradipine will be decreased to 5 mg/day. If ISR side effects are too severe at 5 mg/day, isradipine will be discontinued and the participant will be discharged from the study and referred to local treatment agencies.
Isradipine: Isradipine extended release formulation
|
Placebo
n=7 Urine drug screen results
Placebo will consist of microcrystalline cellulose. Two placebo capsules will be administered per day starting week 1 day 3 through the end of the isradipine taper.
Placebo: Placebo will consist of microcrystalline cellulose.
|
|---|---|---|
|
Change Over Time in Illicit Opioid Use Via Urine Toxicology Screens During Buprenorphine Taper (Wks 5-6)
|
-1.25 opioid-positive urine
Standard Error 0.74
|
-0.36 opioid-positive urine
Standard Error 0.58
|
Adverse Events
Isradipine
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Isradipine
n=11 participants at risk
Isradipine controlled-release formulation, 10 mg/day maintenance dose, will be administered according to the following dose procedures: Isradipine ingestion will occur under supervision 6 days per week, and a take-home dose will be given on Saturday for participants to take on Sunday. The initial dose of isradipine or placebo will be given on Day 3 of Week 1. The initial dose of isradipine will be 5 mg/day; the dose will increase to 10 mg/day on Day 3 of Week 3 and will continue through Day 2 of Week 7. On Day 3 of Week 7, isradipine will be decreased to 5 mg/day for 7 days. On Days 3-5 of Week 8, all participants will receive placebo. If ISR side effects are too severe at the 10-mg dose, isradipine will be decreased to 5 mg/day. If ISR side effects are too severe at 5 mg/day, isradipine will be discontinued and the participant will be discharged from the study and referred to local treatment agencies.
Isradipine: Isradipine extended release formulation
|
Placebo
n=14 participants at risk
Placebo will consist of microcrystalline cellulose. Two placebo capsules will be administered per day starting week 1 day 3 through the end of the isradipine taper.
Placebo: Placebo will consist of microcrystalline cellulose.
|
|---|---|---|
|
Vascular disorders
Flushing
|
27.3%
3/11 • Number of events 3 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
14.3%
2/14 • Number of events 3 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Vascular disorders
Headache
|
36.4%
4/11 • Number of events 4 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
14.3%
2/14 • Number of events 3 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
General disorders
lethargy, drowsiness, sleepiness, tired
|
36.4%
4/11 • Number of events 4 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
28.6%
4/14 • Number of events 5 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Gastrointestinal disorders
vomiting
|
27.3%
3/11 • Number of events 3 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
14.3%
2/14 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Nervous system disorders
Tingling, burning in upper extremities
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Skin and subcutaneous tissue disorders
Rash
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
General disorders
Itchy bug bite(s)
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Musculoskeletal and connective tissue disorders
abdominal pain
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Vascular disorders
swelling in extremities
|
36.4%
4/11 • Number of events 4 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Renal and urinary disorders
Change in urine color
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
0.00%
0/14 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Renal and urinary disorders
Increased urination
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
21.4%
3/14 • Number of events 3 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
General disorders
Night sweats/sweating
|
0.00%
0/11 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
14.3%
2/14 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Vascular disorders
Dizziness, Lightheadedness
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
7.1%
1/14 • Number of events 1 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
|
Gastrointestinal disorders
constipation
|
18.2%
2/11 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
14.3%
2/14 • Number of events 2 • 8 weeks
Participants were queried about their symptoms at every visit and a symptoms form was completed. If the symptom had not been experienced before or was at a greater intensity than experienced previously, then it was considered an adverse event.
|
Additional Information
Alison Oliveto, PhD
University of Arkansas for Medical Sciences
Phone: 501-526-8441
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place