Improving Buprenorphine Detoxification Outcomes With Isradipine

NCT01895270 | Completed Phase 1 Results

• 1 other identifier: R21DA035325
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Opioid Dependence

Keywords

opioid dependence; buprenorphine; isradipine; opioid withdrawal; opioid detoxification

Outcome Measures

Primary Outcomes (1)

• 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

  thrice weekly for approx 2 weeks (taper)

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Isradipine DRUG

Isradipine extended release formulation

Isradipine

Placebo DRUG

Placebo will consist of microcrystalline cellulose.

Also known as: microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UAMS Psychiatric Research Institute

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• 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.

  PMID: 33281447 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Isradipine; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Results are limited by the high dropout rate. Because opioid dependent individuals tend to have relatively low pressure, the feasibility of using an immediate-formulation of a calcium channel blocker is unclear.

Results Point of Contact

• Title: Alison Oliveto, PhD
• Organization: University of Arkansas for Medical Sciences

olivetoalison@uams.edu

501-526-8441

Study Officials

• Alison Oliveto, PhD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: July 10, 2013
• Study Start: October 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-05

Locations

US (1)