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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rajita Sinha, Yale University
ClinicalTrials.gov Identifier:
NCT00142909
First received: September 1, 2005
Last updated: October 27, 2013
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Opioid-Related Disorders
Drug: Lofexidine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • SOWS: the Subjective Opiate Withdrawal Scale [ Time Frame: 1 Week ] [ Designated as safety issue: No ]
    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/

  • SOWS: the Subjective Opiate Withdrawal Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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/


Secondary Outcome Measures:
  • Systolic Blood Pressure [ Time Frame: 1 Week ] [ Designated as safety issue: Yes ]
  • Systolic Blood Pressure [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Diastolic Blood Pressure [ Time Frame: 1 Week ] [ Designated as safety issue: Yes ]
  • Diastolic Blood Pressure [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 86
Study Start Date: February 2005
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00142909

Locations
United States, Connecticut
Yale University, Psychiatry
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Rajita Sinha Yale University
  More Information

No publications provided

Responsible Party: Rajita Sinha, Professor, Yale University
ClinicalTrials.gov Identifier: NCT00142909     History of Changes
Other Study ID Numbers: NIDA-18219-1, R01-18219-1, DPMC
Study First Received: September 1, 2005
Results First Received: November 1, 2012
Last Updated: October 27, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Lofexidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014