Studying Amphetamine Withdrawal in Humans

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT01215929
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 55
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Methamphetamine use is very common in the US and is associated with serious medical and psychiatric problems. There has also been a significant increase in the number of patients entering treatment for methamphetamine dependence, however, no pharmacologic treatment has been identified as effective in treating methamphetamine addiction. Given that withdrawal from methamphetamine is thought to contribute to relapse to methamphetamine use during early treatment, it is important to examine potential pharmacologic agents for alleviating withdrawal. Thus, this study is designed to study methamphetamine withdrawal in humans. To this end, 30 methamphetamine dependent participants (ages 18-65 years) will be entered into a 4-week residential study. Urine samples will be obtained at baseline to ensure recent methamphetamine use. Intake assessments will include cognitive testing, standardized assessment of depression and anxiety, profile of mood states, methamphetamine selective severity assessment, methamphetamine withdrawal assessment, sleep quality and quantity, a pre-attentional measure and attentional measure. Upon admission to the residential facility, all study participants will be started on (20-30mg) long acting amphetamine/d-amphetamine and stabilized over the first 5 days. After stabilization participants will be randomized based on sex, amphetamine withdrawal questionnaire score, and methamphetamine selective severity assessment score to either continued treatment with amphetamine/d-amphetamine or placebo for 2 weeks. All subjects will then be placed on placebo for the last 7 days. The investigators hypothesis is that stopping amphetamine administration in methamphetamine dependent individuals will negatively impact mood, sleep and cognitive function in a time-limited fashion that may differ depending upon the measure and that attentional, but not pre-attentional, measures will be adversely affected in those receiving placebo compared to those maintained on amphetamine.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Drug: Dextroamphetamine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Amphetamine Withdrawal Paradigm in Humans
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dextroamphetamine	Drug: Dextroamphetamine; Thirty treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility and be inducted onto d-amphetamine during week 1 of the study. 15 Participants then will be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.
Placebo Comparator: Placebo	Drug: Placebo; Thirty treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 15 Participants then will be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 week.

Outcome Measures

Primary Outcome Measures

1. Measure of Methamphetamine Withdrawal [at the end of week 4]

   Total score on the Methamphetamine Withdrawal Assessment scale (MAWA) based on DSMIV criteria for amphetamine withdrawal. This questionnaire is comprised of 13 items which describe symptoms associated with the cessation of chronic amphetamine use for which participants indicate severity on a 4-point scale. The minimum score indicating no methamphetamine withdrawal symptoms is 0 and the maximum score is 4 indicating that a patient has the most severe withdrawal symptom related to that question. The subscales are the 13 questions and the total score is the sum of all the scores for the 13 items on the scale. The range minium and better outcome is a lower score. The range is from 0-52. The worse outcome is reflected in a higher score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 21-65 years old

• not currently enrolled in a treatment program

• history of methamphetamine use with recent use confirmed by a positive urine toxicology screen for amphetamines during the month prior to study entry

• self-reported Methamphetamine use on at least 15 of the past 30 days

• use of at least one half gram of methamphetamine per week during the month prior to study entry

• women of childbearing age must have a negative pregnancy test to enroll in this study

Exclusion Criteria:

• current diagnosis of alcohol, opiate, or sedative physical dependence

• ill health (e.g., major cardiovascular, renal, endocrine, hepatic disorder)

• history of schizophrenia, or bipolar type I disorder

• present or recent use of over-the-counter or prescription psychoactive drug or drug(s) that would be expected to have major interaction with d-amphetamine

• medical contraindication to receiving study medications (e.g., previous adverse reaction to d-amphetamine)

• chronic pain condition (due to impact on neurophysiological responses

• current suicidality or psychosis

• liver function tests (i.e., liver enzymes) greater than three times normal levels

• pregnancy or breastfeeding

• children 18-20 will be excluded because the P50 potential is not fully developed in children and adolescents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical SCiences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT01215929
• Other Study ID Numbers: 110743
• First Posted: Oct 7, 2010
• Last Update Posted: Aug 4, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by University of Arkansas: methamphetamine withdrawal; mood; retention; sleep
• Additional relevant MeSH terms: Dextroamphetamine

Study Results

Participant Flow

Arm/Group Title	Dextroamphetamine	Placebo
Arm/Group Description	Dextroamphetamine: Thirty-five treatment-seeking methamphetamine dependent volunteers were admitted to a residential facility and inducted onto d-amphetamine during week 1 of the study. 18 Participants were be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.	Placebo: Thirty-four treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 17 Participants were randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 weeks.
Period Title: Overall Study
STARTED	18	17
COMPLETED	12	12
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Dextroamphetamine	Placebo	Total
Arm/Group Description	Dextroamphetamine: Thirty-five treatment-seeking methamphetamine dependent volunteers were admitted to a residential facility and inducted onto d-amphetamine during week 1 of the study. 18 Participants were be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.	Placebo: Thirty-four treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 17 Participants were randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 weeks.	Total of all reporting groups
Overall Participants	18	17	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.00 (9.76)	33.67 (6.34)	35.36 (8.86)
Sex: Female, Male (Count of Participants)
Female	9 50%	9 52.9%	18 51.4%
Male	9 50%	8 47.1%	17 48.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	18 100%	17 100%	35 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%	17 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Measure of Methamphetamine Withdrawal
Description	Total score on the Methamphetamine Withdrawal Assessment scale (MAWA) based on DSMIV criteria for amphetamine withdrawal. This questionnaire is comprised of 13 items which describe symptoms associated with the cessation of chronic amphetamine use for which participants indicate severity on a 4-point scale. The minimum score indicating no methamphetamine withdrawal symptoms is 0 and the maximum score is 4 indicating that a patient has the most severe withdrawal symptom related to that question. The subscales are the 13 questions and the total score is the sum of all the scores for the 13 items on the scale. The range minium and better outcome is a lower score. The range is from 0-52. The worse outcome is reflected in a higher score.
Time Frame	at the end of week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dextroamphetamine	Placebo
Arm/Group Description	Dextroamphetamine: Thirty-five treatment-seeking methamphetamine dependent volunteers were admitted to a residential facility and inducted onto d-amphetamine during week 1 of the study. 18 Participants were be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.	Placebo: Thirty-five treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 17 Participants were randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 weeks.
Measure Participants	12	12
Least Squares Mean (Standard Error) [units on a scale]	3.7283 (3.37)	10.056 (3.45)

Adverse Events

Arm/Group Title	Dextroamphetamine		Placebo
Arm/Group Description	Dextroamphetamine: Thirty-five treatment-seeking methamphetamine dependent volunteers were admitted to a residential facility and inducted onto d-amphetamine during week 1 of the study. 18 Participants were be randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral d-amphetamine at a dose of 30 mg twice daily for 2 weeks.		Placebo: Thirty-four treatment-seeking methamphetamine dependent volunteers will be admitted to a residential facility in this 4-week, double-blind, placebo-controlled, clinical trial and be inducted onto d-amphetamine during week 1 of the study. 17 Participants were randomized by severity of methamphetamine dependence, sex, amphetamine withdrawal questionnaire score and history of Attention Deficit Hyperactivity Disorder to receive oral placebo tablets twice daily for 2 weeks.
All Cause Mortality
	Dextroamphetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dextroamphetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Dextroamphetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)		9/17 (52.9%)
Cardiac disorders
Tachycardia	3/18 (16.7%)		6/17 (35.3%)
Nervous system disorders
Headache	2/18 (11.1%)		3/17 (17.6%)
Psychiatric disorders
Insomnia	3/18 (16.7%)		2/17 (11.8%)

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.