A Phase 1/2 interventional study of Isradipine and Placebo in Opioid Dependence, sponsored by University of Arkansas. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-06-05.
Sponsored by University of Arkansas · Phase 1/2, Interventional, and Treatment
This application seeks to address the problem of opioid withdrawal by examining the utility of the L-type calcium channel blocker (CCB) isradipine as an adjunct to BUP detoxification. This project will address the need for improved detoxification strategies by assessing the tolerability and preliminary efficacy of adjunct isradipine during a BUP detoxification in opioid-dependent participants. This pilot clinical trial will determine the potential utility of the L-type CCB isradipine to improve treatment outcomes in up to 60 opioid-dependent individuals undergoing a BUP detoxification procedure. Specifically, this study will determine the efficacy of isradipine to reduce withdrawal symptoms, craving, and illicit use of opioids in opioid-dependent individuals undergoing BUP detoxification and determine the tolerability and safety of controlled-release isradipine (10 mg/day) in opioid-dependent individuals undergoing BUP detoxification. Currently, the only FDA-approved medications for opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse liability. Our findings, if positive, will support a larger phase II clinical trial.
Opioid dependence continues to be a serious public health problem, particularly with the dramatic rise in prescription opioid abuse. Traditional methods of detoxification from opioids, including tapering off the opioid agonist methadone or buprenorphine (BUP) and supportive treatment of symptomatology with the alpha2-adrenergic receptor agonists, are limited by the high relapse rate and/or lack of efficacy in relieving subjective symptoms. In addition, transitioning individuals from methadone to BUP maintenance has been limited by the need to drastically taper the methadone maintenance dose of methadone-maintained individuals prior to switching to BUP maintenance, which can precipitate opiate withdrawal and relapse. This application takes a novel approach to address the problem of opioid withdrawal by examining the utility of the L-type calcium channel blocker (CCB) isradipine as an adjunct to BUP detoxification. L-type CCBs have been shown to alleviate opioid withdrawal in opioid-treated nonhumans, to be safe and effective in alleviating withdrawal symptoms in human detoxification trials, and to have low abuse potential. Moreover, isradipine was the most effective of several CCBs tested and was more effective than the alpha2-adrenergic agonist clonidine in blocking naloxone-induced behavioral effects without producing self-reported effects associated with high potential for abuse. Thus, this project will address the need for improved detoxification strategies by assessing the tolerability and preliminary efficacy of adjunct isradipine during a BUP detoxification in opioid-dependent participants. The aim of this 8-week randomized, placebo-controlled pilot clinical trial is to determine the potential utility of the L-type CCB isradipine to improve treatment outcomes in up to 60 opioid-dependent individuals undergoing a BUP detoxification procedure. The specific aims are to (Aim 1) determine the efficacy of isradipine to reduce withdrawal symptoms, craving, and illicit use of opioids in opioid-dependent individuals undergoing BUP detoxification and (Aim 2) determine the tolerability and safety of controlled-release isradipine (10 mg/day) in opioid-dependent individuals undergoing BUP detoxification. Currently, the only FDA-approved medications for opioid withdrawal are the opioid agonists methadone and BUP, both of which have abuse liability. Our findings, if positive, will support a larger phase II clinical trial. Ultimately, this work could impact the addiction field by providing another pharmacological tool that is efficacious for treating opioid withdrawal while having minimal abuse liability. This would shift clinical practice, establishing an effective adjunct regimen for BUP detoxification as well as having the potential to enhance transition to naltrexone therapy.
1,439 studies on the registry are indexed under Opioid-Related Disorders; 291 are open to participants now.
This study's enrollment of 28 is below the median of 62 across 1,145 interventional studies indexed under Opioid-Related Disorders.
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Of its 37 completed or terminated interventional studies of FDA-regulated products, 34 (92%) have results posted.
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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.
Drug: Isradipine
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.
Drug: Placebo
Isradipine extended release formulation
Placebo will consist of microcrystalline cellulose.
Also known as: microcrystalline cellulose
Change Over Time in Illicit Opioid Use Via Urine Toxicology Screens During Buprenorphine Taper (Wks 5-6)
Illicit results via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the taper
Time frame: thrice weekly for approx 2 weeks (taper)
| Milestone | Isradipine | Placebo |
|---|---|---|
| Started | 11 | 14 |
| Completed | 5 | 8 |
| Not completed | 6 | 6 |
| Withdrew: Withdrawal by subject | 0 | 2 |
| Withdrew: Vitals outside of isr dosing parameters | 3 | 2 |
| Withdrew: Noncompliance- missed medications | 3 | 1 |
| Withdrew: Blood pressure issues | 0 | 1 |
| Milestone | Isradipine | Placebo |
|---|---|---|
| Started | 5 | 7 |
| Completed | 2 | 2 |
| Not completed | 3 | 5 |
| Withdrew: Noncompliance - missed medication | 3 | 5 |
| Milestone | Isradipine | Placebo |
|---|---|---|
| Started | 2 | 2 |
| Completed | 2 | 0 |
| Not completed | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
Illicit results via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the taper
| opioid-positive urine | Isradipine | Placebo |
|---|---|---|
| Change Over Time in Illicit Opioid Use Via Urine Toxicology Screens During Buprenorphine Taper (Wks 5-6) | -1.25 ± 0.74 | -0.36 ± 0.58 |
Collected over 8 weeks. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Isradipine | 0/11 (0%) | 0/11 (0%) | 10/11 (90.9%) |
| Placebo | 0/14 (0%) | 0/14 (0%) | 8/14 (57.1%) |
| Event | Isradipine | Placebo |
|---|---|---|
| HeadacheVascular disorders | 4/11 | 2/14 |
| lethargy, drowsiness, sleepiness, tiredGeneral disorders | 4/11 | 4/14 |
| swelling in extremitiesVascular disorders | 4/11 | 0/14 |
| FlushingVascular disorders | 3/11 | 2/14 |
| vomitingGastrointestinal disorders | 3/11 | 2/14 |
| Increased urinationRenal and urinary disorders | 2/11 | 3/14 |
| Tingling, burning in upper extremitiesNervous system disorders | 2/11 | 0/14 |
| RashSkin and subcutaneous tissue disorders | 2/11 | 0/14 |
| Itchy bug bite(s)General disorders | 2/11 | 0/14 |
| abdominal painMusculoskeletal and connective tissue disorders | 2/11 | 0/14 |
These numbers refer to those that actually started the clinical trial proper.
| Age, Categorical(Participants) | Isradipine | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 14 | 25 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Isradipine | Placebo | Total |
|---|---|---|---|
| Female | 5 | 4 | 9 |
| Male | 6 | 10 | 16 |
| Ethnicity (NIH/OMB)(Participants) | Isradipine | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 11 | 14 | 25 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Isradipine | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 11 | 13 | 24 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Isradipine | Placebo | Total |
|---|---|---|---|
| United States | 11 | 14 | 25 |
The record gives a start of Oct 2013, a primary completion of Apr 2016 and a completion of Apr 2016. It does not say whether these dates are actual or estimated.
Results were first posted in Jun 2017, 1 year 2 months after primary completion.
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This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Isradipine