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

Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction

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.

Study Overview

• Status: Completed
• Conditions: Opioid-Related Disorders
• Intervention / Treatment: Drug: Lofexidine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University, Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Placebo Comparator: Drug: Placebo; Placebo pill. Participants will receive daily placebo and will follow the same scheduled delivery as those in the intervention for 12 weeks.	Drug: Placebo; Lofexidine Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SOWS: the Subjective Opiate Withdrawal Scale	The Subjective Opiate Withdrawal Scale (SOWS) consists of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. The total score is a sum of item ratings, and ranges from 0 to 64. The greater the score, the greater the intensity of Opiate Withdrawal. Source: Reprinted from Handelsman et al. 1987, p. 296, by courtesy of Marcel Dekker, Inc.Other Sources: Gossop 1990; Bradley et al. 1987. ACCESSED: http://www.ncbi.nlm.nih.gov/books/NBK64244/	1 Week
SOWS: the Subjective Opiate Withdrawal Scale	The Subjective Opiate Withdrawal Scale (SOWS) consists of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. The total score is a sum of item ratings, and ranges from 0 to 64. The greater the score, the greater the intensity of Opiate Withdrawal. Source: Reprinted from Handelsman et al. 1987, p. 296, by courtesy of Marcel Dekker, Inc.Other Sources: Gossop 1990; Bradley et al. 1987. ACCESSED: http://www.ncbi.nlm.nih.gov/books/NBK64244/	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Systolic Blood Pressure	1 Week
Systolic Blood Pressure	12 weeks
Diastolic Blood Pressure	1 Week
Diastolic Blood Pressure	12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rajita Sinha, Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Opioid dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Peripheral Nervous System Agents; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Narcotic Antagonists; Lofexidine
• Other Study ID Numbers: NIDA-18219-1; DPMC (Other Identifier: NIDA); R01-18219-1