Mod-Nal: Modafinil and Naltrexone to Reduce Cocaine and Alcohol Dependence

• Sponsor: Kyle Kampman (Other)
• Overall Status: Completed
• CT.gov ID: NCT00142818
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 164
• Location: 1
• Arms: 4
• Duration (Months): 90
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Modafinil is a medication that may enhance mood and increase energy in cocaine addicts, which may be useful in preventing cocaine relapse. Naltrexone is a medication that is currently used to treat drug and alcohol addiction. A combination of these two medications may be beneficial in reducing drug and alcohol use in individuals undergoing substance abuse treatment. The purpose of this study is to evaluate the effectiveness of modafinil and naltrexone, alone and in combination, at reducing drug and alcohol use in individuals addicted to cocaine and alcohol.

Condition or Disease	Intervention/Treatment	Phase
Alcohol-Related Disorders; Alcoholism; Cocaine-Related Disorders	Drug: Naltrexone; Drug: Modafinil; Drug: Placebo	Phase 2

Detailed Description

Cocaine and alcohol addiction are serious health problems with no available medical treatment for preventing relapse. Past research has shown that individuals who are addicted to both cocaine and alcohol typically respond poorly to conventional substance abuse treatment. Little attention has been directed towards how best to treat these individuals. Naltrexone is a medication that is currently used to treat drug and alcohol addiction. It acts by blocking the "high" feeling produced by drugs and alcohol. Modafinil, another medication, enhances mood, increases energy, and improves concentration in people with narcolepsy. Preliminary research has shown that it may produce similar effects to cocaine, thereby potentially countering the symptoms of cocaine withdrawal. Cognitive Behavioral Coping Skills Therapy (CBT), a form of therapy that aims to alter an individual's patterns of behavior and drug use, is also an important component of substance abuse treatment. The purpose of this study is to compare the effectiveness of CBT plus placebo, CBT plus modafinil, CBT plus naltrexone, and CBT plus a combination of modafinil and naltrexone at reducing cocaine and alcohol use in individuals addicted to both substances.

This 14-week study will enroll individuals addicted to both cocaine and alcohol. During a 1-week screening period, potential participants will be required to complete a detoxification program, including stopping all cocaine and alcohol use. Participants will also undergo a physical exam and an electrocardiogram. Blood will be drawn for laboratory tests, and urine tests will be used to screen for the presence of drugs and alcohol. Individuals who complete the screening and meet all study requirements will be permitted to participate in the treatment phase of the study. During the 13-week treatment phase, participants will be randomly assigned to receive modafinil, naltrexone, a combination of modafinil and naltrexone, or placebo. All participants will attend a CBT session once a week. Study visits will take place twice a week. At each visit, a urine test and breathalyzer will be used to screen for the presence of alcohol and drugs. Participants will also complete standardized psychological questionnaires to measure drug and alcohol craving, treatment services received, severity of illness, and withdrawal symptoms. In addition, participants will meet weekly with a nurse practitioner, who will dispense study medications, monitor adverse events, and evaluate the participant's clinical status. A follow-up evaluation will occur 6 months following the end of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-blind, Placebo-Controlled, Pilot Trial of the Combination of Modafinil and Naltrexone for the Treatment of Cocaine and Alcohol Dependence
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone plus modafinil Nal + Mod	Drug: Naltrexone; 150 mg daily for males; 100 mg daily for females; Other Names: ReVia ; Drug: Modafinil; 400 mg daily; Other Names: Provigil
Experimental: Naltrexone Nal	Drug: Naltrexone; 150 mg daily for males; 100 mg daily for females; Other Names: ReVia
Experimental: Modafinil Mod	Drug: Modafinil; 400 mg daily; Other Names: Provigil
Placebo Comparator: Placebo Placebo	Drug: Placebo; 400 mg and/or 100-150 mg placebo pills

Outcome Measures

Primary Outcome Measures

1. Cocaine Use (Measured by Timeline Follow Back and Urine Screen From Week 2-week 14) [13 weeks]

2. Percent Days of Heavy Drinking (Measured by Timeline Follow Back Starting at Week Two Through Week 14 [13 weeks]

Eligibility Criteria

Criteria

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

4.1 Inclusion Criteria

1. Male and females, 18 years of age or older.

2. Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID-IV.

3. In the past 30 days, used no less than $200-worth of cocaine and meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995):

4. drank within 30 days of intake day,

5. reports a minimum of 48 standard alcoholic (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and

6. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period.

7. 72 consecutive hours of abstinence from alcohol, determined by self-reports and confirmed by a negative breathalyzer tests, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight. Subjects will be encouraged to achieve 72 consecutive hours of abstinence, however, subjects who have achieved between 48 and 72 consecutive hours of abstinence will be included with the approval of the principal investigator. We anticipate that these subjects will comprise less than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of alcohol abstinence prior to randomization.

8. Lives a commutable distance from the TRC and agrees to attend all research visits including follow-up visits.

9. Speaks, understands, and prints in English

10. Ability to give informed consent

Exclusion Criteria

1. Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent form.

2. Meets DSM IV criteria for dependence on any substance other than cocaine and alcohol (except nicotine), determined by the SCID.

3. Needs treatment with any psychoactive medications including any anti-seizure medications (with the exception of diphenhydramine used sparingly, if necessary, for sleep).

4. Meets current or lifetime DSM-IV criteria for schizophrenia or any psychotic disorder or organic mental disorder. Subject meets current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation.

5. Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease (including a history of myocardial infarction, mitral valve prolapse, left ventricular hypertrophy, uncontrolled hypertension).

6. Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated total bilirubin levels (>1.3 mg/dl),or elevated levels (over 4.5x normal) of aspartate aminotransferase (AST), and serum glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence.

7. Use of an investigational medication in the 30 days prior to randomization.

8. History of hypersensitivity to modafinil or naltrexone

9. Receiving chronic therapy with any drug known to interact adversely with either modafinil or naltrexone including propranolol, phenytoin, warfarin, diazepam

10. Took a monoamine oxidase inhibitor within 30 days of randomization.

11. Is female and tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant). Acceptable methods of contraception include barrier methods (diaphragm or condom with spermicide, female condom), intrauterine progesterone contraceptive system, levonorgrestrel implant, and medroxyprogeterone acetate contraceptive injection, copper IUD, vaginal contraceptive film, cervical cap, contraceptive foam.

12. Current use of an oral contraceptive without other acceptable barrier method of contraception.

13. Received therapy with any opiate substitute (methadone, LAAM, buprenorphine) within 60 days of randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104 6178

Sponsors and Collaborators

• Kyle Kampman
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Kyle M. Kampman, M.D., University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kyle Kampman, Principal Investigator, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00142818
• Other Study ID Numbers: NIDA-12756-3; P50DA012756-03; DPMC
• First Posted: Sep 2, 2005
• Last Update Posted: Jul 16, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Kyle Kampman, Principal Investigator, University of Pennsylvania: Alcohol Abuse; Cocaine Abuse
• Additional relevant MeSH terms: Disease; Alcoholism; Cocaine-Related Disorders; Alcohol-Related Disorders; Naltrexone; Modafinil

Study Results

Participant Flow

Arm/Group Title	ModNal	Naltrexone and Placebo	Modafinil and Placebo	Double Placebo
Arm/Group Description	Nal + Mod Naltrexone: 150 mg daily for males; 100 mg daily for females Modafinil: 400 mg daily	Nal Naltrexone: 150 mg daily for males; 100 mg daily for females	Mod Modafinil: 400 mg daily	Placebo Placebo: 400 mg and/or 100-150 mg placebo pills
Period Title: Overall Study
STARTED	45	40	37	42
COMPLETED	28	19	24	20
NOT COMPLETED	17	21	13	22

Baseline Characteristics

Arm/Group Title	ModNal	Naltrexone and Placebo	Modafinil and Placebo	Double Placebo	Total
Arm/Group Description	Nal + Mod Naltrexone: 150 mg daily for males; 100 mg daily for females Modafinil: 400 mg daily	Nal Naltrexone: 150 mg daily for males; 100 mg daily for females	Mod Modafinil: 400 mg daily	Placebo Placebo: 400 mg and/or 100-150 mg placebo pills	Total of all reporting groups
Overall Participants	45	40	37	42	164
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	45 100%	40 100%	37 100%	42 100%	164 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	15 33.3%	5 12.5%	7 18.9%	14 33.3%	41 25%
Male	30 66.7%	35 87.5%	30 81.1%	28 66.7%	123 75%
Region of Enrollment (participants) [Number]
United States	45 100%	40 100%	37 100%	42 100%	164 100%

Outcome Measures

1. Primary Outcome

Title	Cocaine Use (Measured by Timeline Follow Back and Urine Screen From Week 2-week 14)
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ModNal	Naltrexone and Placebo	Modafinil and Placebo	Double Placebo
Arm/Group Description	Nal + Mod Naltrexone: 150 mg daily for males; 100 mg daily for females Modafinil: 400 mg daily	Nal Naltrexone: 150 mg daily for males; 100 mg daily for females	Mod Modafinil: 400 mg daily	Placebo Placebo: 400 mg and/or 100-150 mg placebo pills
Measure Participants	45	40	37	42
Mean (Standard Deviation) [number of cocaine negative urine samples]	9.3 (8.4)	7.2 (8.1)	10.1 (9.4)	10.5 (9.9)

2. Primary Outcome

Title	Percent Days of Heavy Drinking (Measured by Timeline Follow Back Starting at Week Two Through Week 14
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil Plus Naltrexone	Naltrexone	Modafinil	Placebo
Arm/Group Description	Nal + Mod Naltrexone: 150 mg daily for males; 100 mg daily for females Modafinil: 400 mg daily	Nal Naltrexone: 150 mg daily for males; 100 mg daily for females	Mod Modafinil: 400 mg daily	Placebo Placebo: 400 mg and/or 100-150 mg placebo pills
Measure Participants	45	40	37	42
Mean (Standard Error) [mean percentage of days]	34.7 (4.4)	35.1 (4.2)	33.6 (4.2)	33.8 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ModNal, Naltrexone and Placebo, Modafinil and Placebo, Double Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4
	Comments
	Method	ANOVA
	Comments

Adverse Events

Arm/Group Title	ModNal		Naltrexone and Placebo		Modafinil and Placebo		Double Placebo
Arm/Group Description	Nal + Mod Naltrexone: 150 mg daily for males; 100 mg daily for females Modafinil: 400 mg daily		Nal Naltrexone: 150 mg daily for males; 100 mg daily for females		Mod Modafinil: 400 mg daily		Placebo Placebo: 400 mg and/or 100-150 mg placebo pills
All Cause Mortality
	ModNal		Naltrexone and Placebo		Modafinil and Placebo		Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ModNal		Naltrexone and Placebo		Modafinil and Placebo		Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/45 (24.4%)		6/40 (15%)		6/37 (16.2%)		11/42 (26.2%)
General disorders
Hospitalization	7/45 (15.6%)	9	3/40 (7.5%)	3	3/37 (8.1%)	3	7/42 (16.7%)	11
Exacerbation of cocaine and alcohol	4/45 (8.9%)	4	2/40 (5%)	2	3/37 (8.1%)	3	6/42 (14.3%)	6
Psychiatric disorders
Depression or Hallucinations	1/45 (2.2%)	1	0/40 (0%)	0	0/37 (0%)	0	1/42 (2.4%)	1
Social circumstances
Arrested for Homicide	0/45 (0%)	0	1/40 (2.5%)	1	0/37 (0%)	0	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	ModNal		Naltrexone and Placebo		Modafinil and Placebo		Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/45 (24.4%)		10/40 (25%)		8/37 (21.6%)		4/42 (9.5%)
Gastrointestinal disorders
Nausea	11/45 (24.4%)		10/40 (25%)		8/37 (21.6%)		4/42 (9.5%)
Psychiatric disorders
Anxiety	9/45 (20%)		2/40 (5%)		7/37 (18.9%)		0/42 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.