Effects of Modafinil in Methamphetamine Dependence

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00751023
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 16.9
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

Methamphetamine dependence is a serious public health problem with no pharmacologic treatments currently available. Relapse rates are high in this population. Exposure to cues previously associated with methamphetamine use may induce profound craving in abstinent individuals. Chronic methamphetamine abuse is associated with selective cognitive deficits that may undermine successful participation in psychosocial treatments. Medications which improve cognitive deficits in methamphetamine-dependent individuals may improve abstinence rates, especially in the critical early period of recovery. Modafinil is an atypical stimulant medication with evidence to support its use in treating cocaine dependence and attention deficit/hyperactivity disorder. The proposed studies are designed to evaluate modafinil as a potential treatment for methamphetamine dependence and its cognitive sequelae.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Drug: Modafinil; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Modafinil in Methamphetamine Dependence
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Modafinil 400 mg daily	Drug: Modafinil; 400 mg daily for four weeks; Other Names: Provigil
Placebo Comparator: 2 Placebo	Drug: Placebo; Placebo 2 tablets daily for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Methamphetamine-positive Urine Drug Screens [5 weeks]

   Percentage of participants with at least one biweekly urine drug screen positive for methamphetamine (4 weeks active treatment phase + medication-free safety visit at week 5)

Secondary Outcome Measures

1. Percent Change in California Verbal Learning Test From Baseline to Study Endpoint [Study baseline to study endpoint (Week 5)]

   Mean percent change in T scores (average total score of 6 trials) from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes.

2. Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint [5 Weeks]

   Mean percent change in T scores from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes.

3. Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint [5 weeks]

   Mean percent change of T scores from baseline to study endpoint (Week 5) in study completers. Min T score = 0, max T score = 100. Higher scores, greater (more positive) percent change indicate better outcomes.

4. Score on the Wisconsin Card Sort Test [5 weeks]

   Scores (T scores) on the Wisconsin Card Sort Test (total errors) at study endpoint (Week 5) in study completers, adjusted for age and education; min=0, max=100, higher numbers indicate better outcomes.

5. Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint [5 weeks]

   Percent change of T scores from baseline to study endpoint (Week 5) in study completers; T score min=0, max=100; higher scores (more positive change) indicate better outcome.

6. Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint [5 weeks]

   Percent change in scores (T scores) on the Shipley Abstract subscale from baseline to study endpoint (Week 5) in study completers; T scores min=0, max=100; larger positive values indicate better outcome.

7. Percentage Change in Beck Depression Inventory Scores [5 weeks]

   Percent change in BDI score from baseline to study endpoint in study completers; range =-100% to 100%, larger (more negative) change indicates better outcome.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.

2. Subjects must meet DSM-IV criteria for methamphetamine dependence within the past six months. Subjects may meet criteria for abuse, but not dependence on any other substance with the exception of nicotine. Because of the high comorbidity of methamphetamine and nicotine dependence, excluding nicotine dependence would seriously compromise the feasibility of recruitment. Nicotine use immediately prior to the cue reactivity testing session will be controlled.

3. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for 24 hours prior to the cue reactivity testing sessions.

4. Subjects must consent to random assignment to the modafinil vs. placebo conditions.

Exclusion Criteria:

1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.

2. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease as these conditions may affect heart rate or skin conductance measurement.

3. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may impact cue reactivity.

4. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for 24 hours prior the cue procedures.

5. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine or methamphetamine as appropriate) within the past 60 days.

6. Subjects currently taking B-blockers, anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring.

7. Known or suspected hypersensitivity to modafinil.

8. Individuals taking medications that could adversely interact with study medications.

9. Subjects with a history of epilepsy or seizure disorder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Behavioral Health Services of Pickens County	Pickens	South Carolina	United States	29671

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

• Principal Investigator: Bryan K Tolliver, MD, PhD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00751023
• Other Study ID Numbers: HR#18440
• First Posted: Sep 11, 2008
• Last Update Posted: Jun 13, 2019
• Last Verified: May 1, 2019

• Keywords provided by Medical University of South Carolina: Methamphetamine; Modafinil; Addiction; Craving; Cognitive
• Additional relevant MeSH terms: Modafinil

Study Results

Participant Flow

Pre-assignment Detail	The Enrollment number in the Protocol Section has been corrected (n=40) to appropriately match the number of participants listed in the Results Participant Flow section. The previous Protocol section incorrectly included a cohort (n=31) of healthy control subjects who underwent cognitive testing but did not participate in the modafinil trial.

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Period Title: Overall Study
STARTED	20	20
COMPLETED	9	13
NOT COMPLETED	11	7

Baseline Characteristics

Arm/Group Title	Modafinil	Placebo	Total
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks	Total of all reporting groups
Overall Participants	20	20	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.3 (8.2)	32.1 (7.4)	31.2 (7.8)
Sex: Female, Male (Count of Participants)
Female	14 70%	13 65%	27 67.5%
Male	6 30%	7 35%	13 32.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Methamphetamine-positive Urine Drug Screens
Description	Percentage of participants with at least one biweekly urine drug screen positive for methamphetamine (4 weeks active treatment phase + medication-free safety visit at week 5)
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	20	20
Number [Percentage of participants]	85 425%	65 325%

2. Secondary Outcome

Title	Percent Change in California Verbal Learning Test From Baseline to Study Endpoint
Description	Mean percent change in T scores (average total score of 6 trials) from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes.
Time Frame	Study baseline to study endpoint (Week 5)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	13
Mean (Standard Deviation) [Percent change, baseline-study endpoint]	20.6 (13.4)	14.8 (4.9)

3. Secondary Outcome

Title	Percent Change in Symbol Digit Modalities Test From Baseline to Study Endpoint
Description	Mean percent change in T scores from baseline to study endpoint (Week 5) in study completers. Larger (more positive) percent change values indicate better outcomes.
Time Frame	5 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	13
Mean (Standard Deviation) [Percent change, baseline-study endpoint]	6.4 (15.2)	10.0 (23.6)

4. Secondary Outcome

Title	Percent Change in Paced Auditory Serial Addition Test Scores From Baseline to Study Endpoint
Description	Mean percent change of T scores from baseline to study endpoint (Week 5) in study completers. Min T score = 0, max T score = 100. Higher scores, greater (more positive) percent change indicate better outcomes.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	13
Mean (Standard Deviation) [Percent change, baseline-study endpoint]	11.3 (23.5)	28.5 (61.0)

5. Secondary Outcome

Title	Score on the Wisconsin Card Sort Test
Description	Scores (T scores) on the Wisconsin Card Sort Test (total errors) at study endpoint (Week 5) in study completers, adjusted for age and education; min=0, max=100, higher numbers indicate better outcomes.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

Note: Total number of study completers = 22 (9 in Modafinil group and 13 in Placebo group). The Wisconsin Card Sort Test was able to be completed in only 19 of 22 study completers (8 participants assigned to Modafinil and 11 participants assigned to Placebo).

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	8	11
Mean (Standard Deviation) [T scores at study endpoint]	44.6 (14.0)	41.9 (14.5)

6. Secondary Outcome

Title	Percent Change in the Grooved Pegboard Test Score From Baseline to Study Endpoint
Description	Percent change of T scores from baseline to study endpoint (Week 5) in study completers; T score min=0, max=100; higher scores (more positive change) indicate better outcome.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	13
Mean (Standard Deviation) [Percent change, baseline-study endpoint]	10.8 (40.7)	65.0 (149.9)

7. Secondary Outcome

Title	Percent Change in Shipley Institute of Living Scale Scores From Baseline to Study Endpoint
Description	Percent change in scores (T scores) on the Shipley Abstract subscale from baseline to study endpoint (Week 5) in study completers; T scores min=0, max=100; larger positive values indicate better outcome.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	13
Mean (Standard Deviation) [T scores, percent change]	4.1 (7.1)	4.6 (16.3)

8. Secondary Outcome

Title	Percentage Change in Beck Depression Inventory Scores
Description	Percent change in BDI score from baseline to study endpoint in study completers; range =-100% to 100%, larger (more negative) change indicates better outcome.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

Note: Total number of study completers = 22 (9 in Modafinil group and 13 in Placebo group). Beck Depression Inventory Scores at study endpoint were obtained in only 20 of 22 study completers (9 participants assigned to Modafinil and 11 participants assigned to Placebo).

Arm/Group Title	Modafinil	Placebo
Arm/Group Description	Modafinil 400 mg daily Modafinil: 400 mg daily for four weeks	Placebo Placebo: Placebo 2 tablets daily for 4 weeks
Measure Participants	9	11
Mean (Standard Deviation) [Percent change]	-58.4 (52.7)	-43.5 (35.4)

Adverse Events

Time Frame	Five weeks: Four weeks of active study medication, safety visit one week after medication washout
Adverse Event Reporting Description	Adverse events were systematically collected using a standardized questionnaire at each semi-weekly visit (9 visits total over 5 weeks)
Arm/Group Title	Modafinil		Placebo
Arm/Group Description	Modafinil: 400 mg daily for four weeks		Placebo: 2 tablets daily for four weeks
All Cause Mortality
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Modafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/20 (80%)		14/20 (70%)
Gastrointestinal disorders
Nausea	4/20 (20%)	4	2/20 (10%)	2
Abdominal cramps	0/20 (0%)	0	4/20 (20%)	4
Diarrhea	2/20 (10%)	2	0/20 (0%)	0
General disorders
Insomnia	2/20 (10%)	2	3/20 (15%)	3
Headache	4/20 (20%)	4	1/20 (5%)	1
Common cold symptoms	2/20 (10%)	2	3/20 (15%)	3
Hypersomnia	2/20 (10%)	2	3/20 (15%)	3
Decreased appetite	3/20 (15%)	3	0/20 (0%)	0
Dry mouth / thirst	2/20 (10%)	3	1/20 (5%)	1
Elevated blood pressure	0/20 (0%)	0	2/20 (10%)	2
Infections and infestations
Ear / sinus infection	2/20 (10%)	2	0/20 (0%)	0
Psychiatric disorders
Anxiety	5/20 (25%)	5	2/20 (10%)	2
Skin and subcutaneous tissue disorders
Rash	2/20 (10%)	2	1/20 (5%)	1

Limitations/Caveats

Limited sample size (n=40, n=20 in each group), relatively low retention (55% overall; 45% in modafinil group, 65% in placebo group)

More Information

Certain Agreements

Principal Investigators are NOT 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.