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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00142909
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 86
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Opioid-Related Disorders	Drug: Lofexidine; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. SOWS: the Subjective Opiate Withdrawal Scale [1 Week]

   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/

2. SOWS: the Subjective Opiate Withdrawal Scale [12 weeks]

   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

1. Systolic Blood Pressure [1 Week]

2. Systolic Blood Pressure [12 weeks]

3. Diastolic Blood Pressure [1 Week]

4. Diastolic Blood Pressure [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Yale University, Psychiatry	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Rajita Sinha, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rajita Sinha, Professor, Yale University
• ClinicalTrials.gov Identifier: NCT00142909
• Other Study ID Numbers: NIDA-18219-1; R01-18219-1; DPMC
• First Posted: Sep 2, 2005
• Last Update Posted: Jul 30, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Rajita Sinha, Professor, Yale University: Opioid dependence
• Additional relevant MeSH terms: Opioid-Related Disorders; Lofexidine

Study Results

Participant Flow

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	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.	Participants will receive daily placebo and follow the same schedule as the active intervention for 12 weeks.
Period Title: Randomization
STARTED	42	44
COMPLETED	35	34
NOT COMPLETED	7	10
Period Title: Randomization
STARTED	35	34
COMPLETED	26	31
NOT COMPLETED	9	3

Baseline Characteristics

Arm/Group Title	Lofexidine	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	35	34	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.63 (9.99)	25.56 (7.66)	26.24 (7.96)
Sex: Female, Male (Count of Participants)
Female	8 22.9%	7 20.6%	15 21.7%
Male	27 77.1%	27 79.4%	54 78.3%
Race/Ethnicity, Customized (participants) [Number]
African American	2 5.7%	1 2.9%	3 4.3%
Caucasian	32 91.4%	31 91.2%	63 91.3%
Hispanic	1 2.9%	1 2.9%	2 2.9%
Other	0 0%	1 2.9%	1 1.4%

Outcome Measures

1. Primary Outcome

Title	SOWS: the Subjective Opiate Withdrawal Scale
Description	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/
Time Frame	1 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [units on a scale]	11.5 (9.7)	12.5 (6.7)

2. Secondary Outcome

Title	Systolic Blood Pressure
Time Frame	1 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [mm Hg]	115.3 (10.1)	126.0 (12.0)

3. Primary Outcome

Title	SOWS: the Subjective Opiate Withdrawal Scale
Description	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/
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [units on a scale]	2.9 (5.8)	5.0 (13.3)

4. Secondary Outcome

Title	Systolic Blood Pressure
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [mm Hg]	122.3 (10.1)	126.7 (8.9)

5. Secondary Outcome

Title	Diastolic Blood Pressure
Time Frame	1 Week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [mm Hg]	68.2 (7.6)	73.4 (7.6)

6. Secondary Outcome

Title	Diastolic Blood Pressure
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lofexidine	Placebo
Arm/Group Description	Lofexidine: Study medication	Placebo pill
Measure Participants	26	31
Mean (Standard Deviation) [mm Hg]	74.4 (12.5)	76.1 (7.8)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Lofexidine		Placebo
Arm/Group Description	Lofexidine: Study medication		Placebo pill
All Cause Mortality
	Lofexidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lofexidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Lofexidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/26 (61.5%)		14/31 (45.2%)
Cardiac disorders
Increased Heart Rate	1/26 (3.8%)	1	2/31 (6.5%)	2
Ear and labyrinth disorders
Earache/infection	1/26 (3.8%)	1	2/31 (6.5%)	2
Gastrointestinal disorders
Abdominal Pain	5/26 (19.2%)	5	3/31 (9.7%)	3
Diarrhea	3/26 (11.5%)	3	4/31 (12.9%)	4
Nausea/Vomiting	6/26 (23.1%)	6	5/31 (16.1%)	5
General disorders
Aches	4/26 (15.4%)	4	8/31 (25.8%)	8
Weight Gain/Loss	1/26 (3.8%)	1	2/31 (6.5%)	2
Nervous system disorders
Headache	9/26 (34.6%)	9	10/31 (32.3%)	10
Dizzy/lightheaded	9/26 (34.6%)	9	3/31 (9.7%)	3
Tired/fatigued	12/26 (46.2%)	12	4/31 (12.9%)	4
Psychiatric disorders
Anxiety	1/26 (3.8%)	1	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Sore Throat	3/26 (11.5%)	3	7/31 (22.6%)	7
Cold Symptoms	7/26 (26.9%)	7	10/31 (32.3%)	10
Skin and subcutaneous tissue disorders
Acne	3/26 (11.5%)	3	0/31 (0%)	0
Rash	1/26 (3.8%)	1	2/31 (6.5%)	2
Vascular disorders
Low Blood Pressure	3/26 (11.5%)	3	0/31 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.