Safety and Tolerability of Modafinil for Methamphetamine Dependence

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT00569374
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 8
• Location: 1

Study Details

Study Description

Brief Summary

This 7 week, open-label pilot clinical trial will examine the safety and tolerability of modafinil up to 400mg/day as a potential treatment to reduce methamphetamine use in methamphetamine-dependent volunteers.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine Dependence	Drug: Modafinil	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability of Modafinil for Methamphetamine Dependence
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Sep 1, 2008

Outcome Measures

Primary Outcome Measures

1. Heart Rate [Thrice weekly for 7 weeks]

   Heart rate as a safety measure was measured by thrice weekly measuring heart rate in beats per minute.

2. Systolic Blood Pressure [Thrice weekly for 7 weeks]

   Systolic blood pressure as a safety measure was measured by thrice weekly measuring blood pressure in mmHg.

3. Diastolic Blood Pressure [Thrice weekly for 7 weeks]

   Diastolic blood pressure as a safety measure was measured by thrice weekly measuring blood pressure in mmHg.

4. "Modafinil Side Effects Checklist" [Weekly for 7 weeks]

   Modafinil side effects were measured weekly by means of the Modafinil Side Effects Checklist which asked participants to rate their experience of the following potential side effects: headaches, nausea, nervousness, runny nose, diarrhea, back pain, anxiety, insomnia, dizziness and upset stomach. Participants rated their experience on a 4 point scale ranging from "not at all" (0) to "very much (4). The score was determined by units on a scale.

5. Anxiety as Measured by the Hamilton Anxiety Scale [Thrice weekly for 7 weeks]

   Participants were administered the Hamilton Anxiety Scale thrice weekly throughout the study. The scale is a 14 item questionaire with scores ranging from 0 to 56.

6. Depression as Measured by the Hamilton Depression Scale [Thrice weekly for 7 weeks]

   Participants were administered the Hamilton Depression Scale thrice weekly throughout the study. The scale is a 21 item questionaire with scores ranging from 0 to 62 with a cutoff for depression of 15.

Secondary Outcome Measures

1. Methamphetamine Withdrawal as Measured Using the Amphetamine Withdrawal Questionaire. [Thrice weekly for the first three weeks]

   The Amphetamine Withdrawal Questionaire was given at intake and 3 times weekly during the first 3 weeks of the study. This time span was chosen due to the tendency of methamphetamine withdrawal to enter an acute phase in the first week after last use with a subsequent subacute phase following for the next two weeks(McGregor et al, 2005). This questionaire is comprised of 10 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 is 0 and the maximum score is 40.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18-65 years old

• not currently enrolled in a treatment program

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

• subjects must meet DSM-IV criteria for amphetamine dependence as assessed by the substance abuse section of the Structured Clinical Interview for DSM-IV (SCID)

• women of childbearing age must have a negative pregnancy test to enroll in this study, agree to monthly pregnancy testing, and agree to use appropriate forms of birth control for the duration of the 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 drug to be tested

• medical contraindication to receiving study medications (e.g., allergy to modafinil, treatment with cyclosporine, clomipramine, or desipramine)

• Current suicidality or psychosis

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

• pregnancy or breastfeeding

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
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Dr. Janette McGaugh, MD, University of Arkansas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00569374
• Other Study ID Numbers: Protocol / IRB # 79045
• First Posted: Dec 7, 2007
• Last Update Posted: Oct 5, 2010
• Last Verified: Sep 1, 2010

• Additional relevant MeSH terms: Modafinil

Study Results

Participant Flow

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Period Title: Overall Study
STARTED	8
COMPLETED	4
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (7.2)
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Heart Rate
Description	Heart rate as a safety measure was measured by thrice weekly measuring heart rate in beats per minute.
Time Frame	Thrice weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean heart rate for each participant, then using these to compute the overall mean.

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [beats per minute]	79.66 (2.22)

2. Primary Outcome

Title	Systolic Blood Pressure
Description	Systolic blood pressure as a safety measure was measured by thrice weekly measuring blood pressure in mmHg.
Time Frame	Thrice weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean systolic blood pressure for each participant, then using these to compute the overall mean.

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [mmHg]	128.62 (3.15)

3. Primary Outcome

Title	Diastolic Blood Pressure
Description	Diastolic blood pressure as a safety measure was measured by thrice weekly measuring blood pressure in mmHg.
Time Frame	Thrice weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean diastolic blood pressure for each participant, then using these to compute the overall mean.

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [mmHg]	81.49 (2.67)

4. Primary Outcome

Title	"Modafinil Side Effects Checklist"
Description	Modafinil side effects were measured weekly by means of the Modafinil Side Effects Checklist which asked participants to rate their experience of the following potential side effects: headaches, nausea, nervousness, runny nose, diarrhea, back pain, anxiety, insomnia, dizziness and upset stomach. Participants rated their experience on a 4 point scale ranging from "not at all" (0) to "very much (4). The score was determined by units on a scale.
Time Frame	Weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtainined by computing the overall mean numberical score on the Modafinil Side Effects Checklist for each participant, then using these to compute the overall mean. The checklist is a 10 item scale with each item scoring between 0 (none) to 4 (worst). The potential scores range from 0 (least) to 40 (worst).

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [units on a scale]	3.75 (2.94)

5. Primary Outcome

Title	Anxiety as Measured by the Hamilton Anxiety Scale
Description	Participants were administered the Hamilton Anxiety Scale thrice weekly throughout the study. The scale is a 14 item questionaire with scores ranging from 0 to 56.
Time Frame	Thrice weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean score on the Hamilton Anxiety Scale for each participant, then using these to compute the overall mean. The scale is a 14 item instrument with each item scoring a potential range of 0 (none) to 4 (worst). The potential total scores range form 0 (least) to 56 (worst).

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [units on a scale]	4.07 (2.44)

6. Primary Outcome

Title	Depression as Measured by the Hamilton Depression Scale
Description	Participants were administered the Hamilton Depression Scale thrice weekly throughout the study. The scale is a 21 item questionaire with scores ranging from 0 to 62 with a cutoff for depression of 15.
Time Frame	Thrice weekly for 7 weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean score on the Hamilton Depression Scale for each participant, then using these to compute the overall mean. It is a 22 item scale of which 13 items have a score of 0 (none) to 4 (worst) and 9 have a score of 0 (none) to 2 (worst). The total score ranges from 0 (least) to 70 (worst).

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [units on a scale]	5.64 (3.41)

7. Secondary Outcome

Title	Methamphetamine Withdrawal as Measured Using the Amphetamine Withdrawal Questionaire.
Description	The Amphetamine Withdrawal Questionaire was given at intake and 3 times weekly during the first 3 weeks of the study. This time span was chosen due to the tendency of methamphetamine withdrawal to enter an acute phase in the first week after last use with a subsequent subacute phase following for the next two weeks(McGregor et al, 2005). This questionaire is comprised of 10 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 is 0 and the maximum score is 40.
Time Frame	Thrice weekly for the first three weeks

Outcome Measure Data

Analysis Population Description

The data reported was obtained by computing the overall mean numerical score on the Amphetamine Withdrawal Questionaire for each participant, then using these to compute the overall mean. The scale consists of 13 items ranging from 0 (none) to 4 (worst). The total score ranges from 0 (least) to 52 (worst).

Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
Measure Participants	8
Mean (Standard Deviation) [units on a scale]	5.79 (4.42)

Adverse Events

Time Frame	These results were collected over a period of 1 year and 10 months. Five Adverse events occurred during the study, of which three were probably related to study participation.
Adverse Event Reporting Description	Adverse events included one report each of tachycardia and dry mouth. The third occurred when a subject missed a dose on one day and took a double dose the next day. The subject experienced tachycardia, dry mouth, nervousness which resolved within one hour of modafinil ingestion.
Arm/Group Title	Modafinil
Arm/Group Description	All participants were started on Modafinil titrated to 400mg in this open label trial.
All Cause Mortality
	Modafinil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Modafinil
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Modafinil
	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)
General disorders
Tachycardia	1/8 (12.5%)	1
Dry mouth	1/8 (12.5%)	1
Tachycardia, dry mouth, nervousness after taking extra dose	1/8 (12.5%)	1

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.