Improving Buprenorphine Detoxification Outcomes With Isradipine

Opioid Dependence Clinical Trial

Official title:

Improving Buprenorphine Detoxification Outcomes With Isradipine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01895270
• Other study ID #: R21DA035325
• Secondary ID: R21DA035325
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 25, 2013
• Last updated: April 18, 2016
• Start date: October 2013
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: University of Arkansas
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Availability to attend clinic 6 days a week for approximately 30-60 minutes per day.

2. 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.

3. Participants must submit a urine sample negative for drugs of abuse other than opioids or marijuana prior to starting the study.

Exclusion Criteria:

1. Unstable medical condition or stable medical condition that would interact with study medications or participation.

2. History of major psychiatric disorder (psychosis, schizophrenia, bipolar)

3. Pregnancy or plans to become pregnant or inadequate birth control (adequate birth control includes abstinence, condoms, birth control pills, etc).

4. 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.

5. Liver function tests greater than 3 times normal; BUN and Creatinine outside normal range.

6. 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.

7. Physical dependence on alcohol or drugs other than opioids, marijuana or tobacco (as determined by physician assessment).

8. Pre-existing severe gastrointestinal narrowing.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Opioid Dependence
• Opioid-Related Disorders

Intervention

Drug:
• Isradipine
Isradipine extended release formulation
• Placebo
Placebo will consist of microcrystalline cellulose.

Locations

Country	Name	City	State
United States	UAMS Psychiatric Research Institute	Little Rock	Arkansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Arkansas	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change over time in Illicit Opioid Use via Urine Toxicology Screens	Illicit opioid use via urine toxicology screens for heroin and several opioids will be measured thrice weekly during the trial.	thrice weekly for 8 weeks	No
Secondary	change over time in orthostatic vital signs	orthostatic vital signs will be done at least once weekly to determine the incidence of orthostatic hypotension	once weekly for 8 weeks	Yes