Opioid DependencePhase 1/2NCT01895270
Improving Buprenorphine Detoxification Outcomes With Isradipine
A Phase 1/2 study testing Isradipine in people with Opioid Dependence, run by University of Arkansas at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Dependence
- What is being tested?
- Isradipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Apr 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Availability to attend clinic 6 days a week for approximately 30-60 minutes per day.
- Participants must fulfill DSM-IV criteria for opioid dependence. These criteria will be ascertained in the following manner: the physician will determine whether the individual is appropriate based on several clinical assessments that are routinely employed by methadone program physicians, including history and severity of opioid use, presence of track marks, prior treatment history, self-reported and/or observed signs and symptoms of opioid withdrawal. If any individual's degree of opioid dependence is questionable, that person will be excluded from further consideration as a participant.
- Participants must submit a urine sample negative for drugs of abuse other than opioids or marijuana prior to starting the study.
Who cannot join
- Unstable medical condition or stable medical condition that would interact with study medications or participation.
- History of major psychiatric disorder (psychosis, schizophrenia, bipolar)
- Pregnancy or plans to become pregnant or inadequate birth control (adequate birth control includes abstinence, condoms, birth control pills, etc).
- Present or recent use of over-the-counter psychoactive drug, prescription psychoactive drug or any drug that would have major interaction with drugs to be tested.
- Liver function tests greater than 3 times normal; BUN and Creatinine outside normal range.
- EKG abnormalities including but not limited to: bradycardia (<60 bpm); prolonged QTc interval (>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block.
- Physical dependence on alcohol or drugs other than opioids, marijuana or tobacco (as determined by physician assessment).
- Pre-existing severe gastrointestinal narrowing.
Trial locations and contacts
1 site in 1 country.
United States1 site
UAMS Psychiatric Research Institute
Little Rock, Arkansas, 72205
About this study
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.
Read the detailed description
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.
- Conditions
- Opioid Dependence
- Being tested
- Isradipine, Placebo
- Keywords
- opioid dependence, buprenorphine, isradipine, opioid withdrawal, opioid detoxification
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsradipineDrug
Isradipine extended release formulation
PlaceboDrug
Also called microcrystalline cellulose
Placebo will consist of microcrystalline cellulose.
| Study group | Role | What they receive |
|---|---|---|
| Isradipine | Experimental | 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. Receives: Drug: Isradipine |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: thrice weekly for approx 2 weeks (taper)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startOct 2013
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid DependenceStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Alison Oliveto, PhD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895270
- Sponsor's protocol ID
- R21DA035325
- Other IDs
- R21DA035325
- Status last verified
- May 2017
- First submitted
- 25 Jun 2013
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kumar N, Mancino MJ, Thostenson JD, McGaugh J, Oliveto AH. Feasibility and Preliminary Efficacy of Isradipine During Outpatient Buprenorphine Stabilization and Detoxification: A Pilot Randomized, Placebo-Controlled Trial. Subst Abuse. 2020 Nov 23;14:1178221820970926. doi: 10.1177/1178221820970926. eCollection 2020.
PubMed 33281447
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Buprenorphine Detoxification Outcomes With Isradipine
- ClinicalTrials.gov ID
- NCT01895270
- Acronym / sponsor ID
- R21DA035325
- Conditions
- Opioid Dependence
- Keywords
- opioid dependence, buprenorphine, isradipine, opioid withdrawal, opioid detoxification
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Oct 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isradipine | Experimental | Drug: IsradipineIsradipine 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Availability to attend clinic 6 days a week for approximately 30-60 minutes per day.
- Participants must fulfill DSM-IV criteria for opioid dependence. These criteria will be ascertained in the following manner: the physician will determine whether the individual is appropriate based on several clinical assessments that are routinely employed by methadone program physicians, including history and severity of opioid use, presence of track marks, prior treatment history, self-reported and/or observed signs and symptoms of opioid withdrawal. If any individual's degree of opioid dependence is questionable, that person will be excluded from further consideration as a participant.
- Participants must submit a urine sample negative for drugs of abuse other than opioids or marijuana prior to starting the study.
Key exclusion criteria (8 listed)
- Unstable medical condition or stable medical condition that would interact with study medications or participation.
- History of major psychiatric disorder (psychosis, schizophrenia, bipolar)
- Pregnancy or plans to become pregnant or inadequate birth control (adequate birth control includes abstinence, condoms, birth control pills, etc).
- Present or recent use of over-the-counter psychoactive drug, prescription psychoactive drug or any drug that would have major interaction with drugs to be tested.
- Liver function tests greater than 3 times normal; BUN and Creatinine outside normal range.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsradipineIsradipine extended release formulation | Drug | Isradipine |
| PlaceboAlso: microcrystalline cellulosePlacebo will consist of microcrystalline cellulose. | Drug | Placebo |
Primary outcome
Change Over Time in Illicit Opioid Use Via Urine Toxicology Screens During Buprenorphine Taper (Wks 5-6)
Time frame: thrice weekly for approx 2 weeks (taper)
Illicit results via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the taper
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33281447Kumar N, Mancino MJ, Thostenson JD, McGaugh J, Oliveto AH. Feasibility and Preliminary Efficacy of Isradipine During Outpatient Buprenorphine Stabilization and Detoxification: A Pilot Randomized, Placebo-Controlled Trial. Subst Abuse. 2020 Nov 23;14:1178221820970926. doi: 10.1177/1178221820970926. eCollection 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Oliveto, PhD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Isradipine in people with Opioid Dependence, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change Over Time in Illicit Opioid Use Via Urine Toxicology Screens During Buprenorphine Taper (Wks 5-6) (time frame: thrice weekly for approx 2 weeks (taper)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01895270, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017; AzTrials last refreshed its copy on 4 Nov 2026.