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

Study Overview
=================
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.

Official Title
-----------------
Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction

Conditions
-----------------
Opioid-Related Disorders

Intervention / Treatment
-----------------
* Drug: Lofexidine
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure |  | 1 Week | 
| Systolic Blood Pressure |  | 12 weeks | 
| Diastolic Blood Pressure |  | 1 Week | 
| Diastolic Blood Pressure |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Opioid dependence