ATM: Clinical Efficacy of Atomoxetine for Methamphetamine Dependence

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT01557569
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the ability of atomoxetine compared to placebo to increase time to relapse in methamphetamine dependent volunteers. Our hypothesis is that atomoxetine will increase time before (if) the participant relapses.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Drug: Atomoxetine; Drug: placebo	Phase 1/Phase 2

Detailed Description

During the study participants will spend the initial 2-weeks of the study at an inpatient facility. This will help participants initiate withdrawal. During the following 8-weeks the participant will come in for 3-4 visits each week. Three of these visits will be with the research assistants and one visit will be with a therapist in order to work with the participant using a cognitive behavioral therapy approach. Therapy visits are typically scheduled on a day that the participant is coming for clinic anyways so the number of visits per week is typically 3. During the 10-week period the investigators will collect various measures, including vitals, cognitive assessments, mood assessments, urine drug screens, weekly use reports of methamphetamine, and any reports of symptoms or side effects. This will tell the investigators if atomoxetine is safe and if a participant lapsed or relapsed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atomoxetine Group receiving atomoxetine	Drug: Atomoxetine; During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7); Other Names: strattera
Placebo Comparator: Placebo Group will receive placebo instead of atomoxetine	Drug: placebo; participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.; Other Names: "sugar pill"

Outcome Measures

Primary Outcome Measures

1. Time Till Relapse [57 days]

   The number of days until a participant has a relapse, which will be measured by qualitative urine drug screens. To ensure a large enough sample, those who drop out prior to completing the residential stay will be included in this analysis (with minus days until relapse)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria.

• 18-65 years old

• Seeking treatment for METH use

• METH dependence, as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV.

• At least weekly self-reported METH use during a preceding three month period

• Women of childbearing age must have a negative pregnancy test, agree to adequate contraception to prevent pregnancy during the study, agree to monthly pregnancy testing, and not be nursing

• Men must agree to use effective means of contraception during the study.

Exclusion Criteria.

• Suicide attempts within the past 12 months or either suicidal ideations or psychotic symptoms in the past 6 months as determined by a study physician.

• Current opioid, alcohol or sedative physical dependence or cocaine dependence

• Major cardiovascular disorder that contraindicates study participation (e.g., history of myocardial infarction, stroke, congestive heart failure, cardiac arrhythmia, hypertension [i.e., > 160 SBP or > 100 DBP] or an unstable medical condition (e.g., untreated bacterial infection) as determined by the study physician.

• Schizophrenia or bipolar disorder of any type

• Present or recent use (within 2 weeks) of over-the-counter or prescription drug that would be expected to have major interaction with atomoxetine (e.g., an monoamine oxidase inhibitor (MAOI), paroxetine, fluoxetine, quinidine, dopamine, albuterol, or other β2-agonists)

• Medical contraindication to receiving atomoxetine (e.g., severe hepatic impairment, glaucoma, heart disease, hypertension, seizure disorders, documented hypersensitivity to atomoxetine); or other bronchospastic condition, (2nd or 3rd degree AV block, sick sinus rhythm, severe hepatic impairment, documented hypersensitivity to atomoxetine)

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

• Systolic blood pressure of < 90 or > 160 mmHg, diastolic blood pressure of < 60 or > 100 mmHg, or sitting heart rate of < 55 or > 100 beats/min or blood pressure readings

140 systolic or > 90 diastolic on three separate, consecutive occasions.

• History of pheochromocytoma

• Pregnant or nursing female

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAMS, Psychiatric Research Institute, Center for Addiction Research	Little Rock	Arkansas	United States	72034

Sponsors and Collaborators

• University of Arkansas
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Alison Oliveto, PhD, University of Arkansas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT01557569
• Other Study ID Numbers: 133414
• First Posted: Mar 19, 2012
• Last Update Posted: Feb 9, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by University of Arkansas: methamphetamine; addiction; relapse; atomoxetine
• Additional relevant MeSH terms: Atomoxetine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Atomoxetine	Placebo
Arm/Group Description	Group receiving atomoxetine Atomoxetine: During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7)	Group will receive placebo instead of atomoxetine placebo: participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.
Period Title: Overall Study
STARTED	6	7
Completed 2-wk Residential Stay	3	1
COMPLETED	1	0
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Atomoxetine	Placebo	Total
Arm/Group Description	Group receiving atomoxetine Atomoxetine: During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7)	Group will receive placebo instead of atomoxetine placebo: participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.	Total of all reporting groups
Overall Participants	6	7	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	7 100%	13 100%
>=65 years	0 0%	0 0%	0 0%
Gender (Count of Participants)
Female	2 33.3%	3 42.9%	5 38.5%
Male	4 66.7%	4 57.1%	8 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	7 100%	13 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	7 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Time Till Relapse
Description	The number of days until a participant has a relapse, which will be measured by qualitative urine drug screens. To ensure a large enough sample, those who drop out prior to completing the residential stay will be included in this analysis (with minus days until relapse)
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

Only 4 of 13 finished the 2-week residential stay. Since subjects who drop out are deemed relapsed, all subjects receiving >/=1 dose of study med were included in the analyses. Those who dropped out before completing the residential stay were considered relapsed by the second day and the date of discharge was subtracted from this relapse date.

Arm/Group Title	Atomoxetine	Placebo
Arm/Group Description	Group receiving atomoxetine Atomoxetine: During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7)	Group will receive placebo instead of atomoxetine placebo: participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.
Measure Participants	6	7
Median (Full Range) [Days to Relapse]	7	-8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine, Placebo
	Comments	Due to skewed data, Kruskal Wallis Test was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Kruskal-Wallis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.413
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Atomoxetine		Placebo
Arm/Group Description	Group receiving atomoxetine Atomoxetine: During the first 2 weeks and three days the dose of atomoxetine will be titrated up starting with 20 mg/day for first 3 days, 36 mg/day for next 4 days, 50 mg/day for next 3 days, and finally 80 mg/day until the final day of the study (week 10, day 7)		Group will receive placebo instead of atomoxetine placebo: participants in this group will receive 1 dose of placebo daily for the entire 10-weeks.
All Cause Mortality
	Atomoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atomoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Atomoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		2/7 (28.6%)
Cardiac disorders
elevated BP (outside parameters)	0/6 (0%)	0	1/7 (14.3%)	1
elevated BP on 3 separate occasions	0/6 (0%)	0	1/7 (14.3%)	2
rapid heartbeat	2/6 (33.3%)	3	0/7 (0%)	0
chest pain	1/6 (16.7%)	1	0/7 (0%)	0
Gastrointestinal disorders
constipation	1/6 (16.7%)	1	0/7 (0%)	0
nausea/vomiting	1/6 (16.7%)	1	0/7 (0%)	0
General disorders
sleepiness/tiredness	1/6 (16.7%)	1	1/7 (14.3%)	1
night sweats	1/6 (16.7%)	1	0/7 (0%)	0
insomnia	2/6 (33.3%)	2	0/7 (0%)	0
dry mouth	1/6 (16.7%)	1	0/7 (0%)	0
hot flash	1/6 (16.7%)	1	0/7 (0%)	0
labored breathing	1/6 (16.7%)	1	0/7 (0%)	0
Nervous system disorders
sharp apin/tingling in limb	1/6 (16.7%)	1	0/7 (0%)	0
headache/pain	1/6 (16.7%)	2	0/7 (0%)	0
Psychiatric disorders
anxiety	1/6 (16.7%)	1	0/7 (0%)	0
irritability	1/6 (16.7%)	1	0/7 (0%)	0

Limitations/Caveats

Recruitment and retention was much more difficult than anticipated. Because of, this too few (3 in ATM and 1 in PLA) were retained through the residential stay to determine efficacy.

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.