Effectiveness of Lofexidine to Prevent Stress-Related Opiate Relapse During Naltrexone Treatment - 1

NCT ID: NCT00142909

Last Updated: 2015-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2009-01-31

Brief Summary

Lofexidine is an experimental medication that may be beneficial in reducing opiate withdrawal symptoms, such as sleep difficulty, anxiety, and tension. The purpose of this study is to determine whether lofexidine in combination with naltrexone can improve an individual's ability to cope with stress and subsequently increase the chances of remaining abstinent from opiates.

Detailed Description

Naltrexone is a medication currently used to treat opiate dependence. Naltrexone blocks the euphoric effects of opiates. However, naltrexone treatment suffers from high rates of drop-out and relapse. One possible explanation for this is that opiate addicts continue to experience stress in early recovery from opiate dependence. Lofexidine is an experimental medication currently used in the United Kingdom for opiate detoxification and to treat opiate withdrawal symptoms, including sleep difficulty, muscle pain, anxiety, and tension. The purpose of this study is to examine whether lofexidine in combination with naltrexone can improve an individual's ability to cope with stress. The study will examine whether this, in turn, increases the likelihood that an individual remains abstinent from opiates and maintains recovery for a longer time period.

Participants in this 12-week, double-blind, placebo-controlled trial will be randomly assigned to receive either lofexidine or placebo while currently receiving standard naltrexone outpatient treatment. Lofexidine will be initiated at twice daily doses of 0.4 mg and increased to 0.8 mg by the end of Week 1. The doses will be increased to 1.2 mg by the end of Week 2, and maintained at this level for Weeks 3 through 12. During Week 12, lofexidine discontinuation will be tapered over 4 days. Hour-long study visits will occur 3 times each week to assess vital signs, medication side effects, and withdrawal symptoms. Blood, alcohol, and urine tests will be performed as well as a psychiatric evaluation. Administration of naltrexone will also occur 3 times each week. Follow-up visits will occur at Months 1 and 3 after discontinuation of lofexidine.

Conditions

Opioid-Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Drug: Lofexidine

Lofexidine: Study medication

Participants will receive daily lofexidine and the dosing will be initiated at 0.4 mg bid and increased to 0.8mg in week 1 and 1.0 and 1.2 mg bid in week 2, and maintained at 1.2mg bid for weeks 3 to 12. They are then tapered down to 0 over the course of four days in week 12. While the target dose will be 2.4 mg daily, if any subject shows reduced tolerability at this or a lower dose, the dose will be adjusted to the maximum tolerated dose for that subject.

Group Type: EXPERIMENTAL

Lofexidine

Intervention Type: DRUG

Participants will receive lofexidine. The dosing will be initiation at 0.4 mg bid and increased to 0.8mg in week 1 and 1.0 and 1.2 mg bid in week 2, and maintained at 1.2mg bid for weeks 3 to 12. They are then tapered down to 0 over the course of four days in week 12. While the target dose will be 2.4 mg daily, if any subject shows reduced tolerability at this or a lower dose, the dose will be adjusted to the maximum tolerated dose for that subject.

Drug: Placebo

Placebo pill.

Participants will receive daily placebo and will follow the same scheduled delivery as those in the intervention for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Lofexidine Placebo

Interventions

Lofexidine

Participants will receive lofexidine. The dosing will be initiation at 0.4 mg bid and increased to 0.8mg in week 1 and 1.0 and 1.2 mg bid in week 2, and maintained at 1.2mg bid for weeks 3 to 12. They are then tapered down to 0 over the course of four days in week 12. While the target dose will be 2.4 mg daily, if any subject shows reduced tolerability at this or a lower dose, the dose will be adjusted to the maximum tolerated dose for that subject.

Intervention Type: DRUG

Placebo

Lofexidine Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Meets DSM-IV criteria for opioid dependence
• Eligible to take a daily dose of 50 mg of naltrexone
• Normal EKG
• Able to read English

Exclusion Criteria

• Currently psychotic or psychiatrically disabled (e.g., suicidal, homicidal, manic)
• Regular use of anticonvulsants, sedatives/hypnotics, prescription analgesics, antihypertensives (including clonidine), antiarrhythmics, antiretroviral medications, or tricyclic antidepressants
• Underlying medical conditions, such as cerebral, kidney, thyroid, or cardiac pathology, and currently taking medications for any of these conditions
• Abstinent from opiates for more than 4 weeks prior to initiation of naltrexone
• Medical problems precluding naltrexone treatment, such as hepato-cellular injury, as evidenced by abnormal liver enzyme tests (greater than three times the normal level) and a history of cirrhosis
• Hypotensive (resting blood pressure below 90/50 mm Hg)
• Pregnant or breastfeeding
• Use of an investigational drug within the 3 months prior to enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Rajita Sinha

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajita Sinha

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University, Psychiatry

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

R01-18219-1

Identifier Type: -

Identifier Source: secondary_id

DPMC

Identifier Type: -

Identifier Source: secondary_id

NIDA-18219-1

Identifier Type: -

Identifier Source: org_study_id