Pioglitazone to Treat Opioid Withdrawal Symptoms

NCT01517165 | Terminated Phase 1

• 2 other identifiers: 99991246912-DA-N469
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Opioid-withdrawal symptoms include runny nose, body aches, chills, sweating, and diarrhea. Many people have these symptoms when trying to stop using opioid drugs. Long-acting opioids like methadone and buprenorphine are used to help people stop using other opioids, but these drugs can cause the same withdrawal symptoms. There are no non-opioid drugs that are approved specifically to treat those symptoms.
• Pioglitazone is a drug used to treat type 2 diabetes. In a research study, the drug allowed heroin users to decrease their methadone dose faster without much discomfort, and stay abstinent from heroin. Researchers want to learn more about how pioglitazone helps treat opioid withdrawal symptoms. Objectives: \- To test whether pioglitazone can reduce opioid withdrawal symptoms. Eligibility: \- Individuals between 18 and 65 years of age who will be using buprenorphine to treat opioid dependency. Design:
• This study will last up to 17 weeks. Participants must come to the study clinic every day for at least 13 weeks.
• Participants will be screened with a physical exam and medical history. They will also answer questions about drug use habits, and provide blood and urine samples.
• Participants will take buprenorphine daily for 7 weeks. For the first 3 weeks, the dose will be increased to a level that should help stop the use of opioids. For the next 4 weeks, the dose will be decreased. Blood, urine, and breath samples will be collected at different study visits. Participants will also fill out questionnaires about mood, drug craving, and withdrawal symptoms.
• After 1 week on buprenorphine, participants will start the study pill (pioglitazone or a placebo) every day. They will take the study pill for 13 weeks.
• During the treatment period, participants will have drug counseling once a week for 30 minutes.
• Some participants have other tests as part of this study. These tests include functional magnetic resonance imaging scans to look for changes in brain activity and giving samples of cerebrospinal fluid to study brain chemistry.
• Participants will have a final followup phone call 3 weeks after the last clinic visit.

Conditions

Opioid-Related Disorders

Keywords

Opioid Dependence; Pioglitazone; Buprenorphine

Outcome Measures

Primary Outcomes (1)

• Treatment response, defined as opioid abstinence without severe withdrawal symptoms during the last week of the taper (week 6) and duration in treatment (retention)

Secondary Outcomes (1)

• Overall proportions of opioid-negative urines, proportions of participants needing adjunct medications status at follow-up

Study Arms (2)

Group 1

EXPERIMENTAL

Drug: Pioglitazone

Group 2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Pioglitazone DRUG

Group 1

Placebo DRUG

Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65
• Evidence of physical dependence on opioids (determined by a combination of self-report, urine screen, and/or physical exam)
• Seeking detoxification treatment for opioid dependence
• Able to attend the clinic 7 days/week and undergo an 18-day residential stay
• For women:
• post-menopausal or surgically sterile (tubal ligation or hysterectomy) or
• if sexually active with a male partner and able to get pregnant, documented agreement to use an IRB-approved form of birth control. Acceptable forms of contraception for this study include: hormonal contraceptives (birth-control pills, injectable hormones, vaginal-ring hormones); IUD; diaphragm with spermicide; condom with spermicide.

You may not qualify if:

• Any medical illness that in the view of the investigators would compromise participation in research (determined by Medical History; Physical Examination; Blood and Urine Laboratory tests; see details under Screening measures below), including, but not limited to:
• Diabetes mellitus Type I or Type II
• Past or current diagnosis of congestive heart failure
• Signs and symptoms consistent with congestive heart failure including but not limited to fatigue, exercise intolerance, decreased peripheral perfusion, orthopnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, peripheral edema, elevated jugular-venous pressure, pleural and pericardial effusions, hepatic congestion, ascites, elevated BUN and creatinine, hyponatremia, and elevated serum levels of hepatic enzymes.
• Cardiovascular disease (e.g., history of congenital heart defect, heart disease, symptomatic coronary-artery disease, heart attack, irregular heartbeat, etc.)
• Cerebrovascular disease
• Unexplained history of syncope
• History of seizures, except for febrile seizures at childhood
• History of head injury with loss of consciousness of more than 30 minutes or with postconcussive sequelae lasting more than two days, regardless of loss of consciousness
• Chronic renal failure as estimated by glomerular filtration rate (GFR) \<60 mL/min/1.73 m(2)
• CD4 \< 200 or evidence of severely compromised immune system /AIDS
• Active bladder cancer or history of bladder cancer
• Allergy, hypersensitivity, or intolerance to buprenorphine, pioglitazone, other TZDs, or the metabolites of any of those drugs (determined by Medical History)
• Pregnancy or breastfeeding (Urine Pregnancy Test; self-report)
• Diabetes medications (e.g., sulfonylureas, metformin, insulin, etc.)

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (4)

• Alvarez RP, Chen G, Bodurka J, Kaplan R, Grillon C. Phasic and sustained fear in humans elicits distinct patterns of brain activity. Neuroimage. 2011 Mar 1;55(1):389-400. doi: 10.1016/j.neuroimage.2010.11.057. Epub 2010 Nov 25.

  PMID: 21111828 BACKGROUND

• Back SE, Hartwell K, DeSantis SM, Saladin M, McRae-Clark AL, Price KL, Moran-Santa Maria MM, Baker NL, Spratt E, Kreek MJ, Brady KT. Reactivity to laboratory stress provocation predicts relapse to cocaine. Drug Alcohol Depend. 2010 Jan 1;106(1):21-7. doi: 10.1016/j.drugalcdep.2009.07.016. Epub 2009 Sep 2.

  PMID: 19726138 BACKGROUND

• Cardenas VA, Studholme C, Gazdzinski S, Durazzo TC, Meyerhoff DJ. Deformation-based morphometry of brain changes in alcohol dependence and abstinence. Neuroimage. 2007 Feb 1;34(3):879-87. doi: 10.1016/j.neuroimage.2006.10.015. Epub 2006 Nov 28.

  PMID: 17127079 BACKGROUND

• Schroeder JR, Phillips KA, Epstein DH, Jobes ML, Furnari MA, Kennedy AP, Heilig M, Preston KL. Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder. Psychopharmacology (Berl). 2018 Oct;235(10):2957-2966. doi: 10.1007/s00213-018-4986-5. Epub 2018 Aug 6.

  PMID: 30079432 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kenzie Preston, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 25, 2012
• Study Start: January 4, 2012
• Primary Completion: February 2, 2015
• Study Completion: February 2, 2015
• Last Updated: July 5, 2018

Record last verified: 2015-02-02

Locations

US (1)