Acamprosate in the Treatment of Pathological Gambling

• Sponsor: University of Iowa (Other)
• Overall Status: Completed
• CT.gov ID: NCT00571103
• Collaborator: University of Nebraska (Other), Forest Laboratories (Industry)
• Enrollment: 26
• Arm: 1
• Duration (Months): 21

Study Details

Study Description

Brief Summary

The purpose of this study is to see whether acamprosate (Campral) will curb the desire to gamble in people with pathological gambling disorder.

Condition or Disease	Intervention/Treatment	Phase
Pathological Gambling	Drug: acamprosate	Phase 4

Detailed Description

Because the opiate antagonists appear to be effective in the treatment of pathological gambling (PG), it is reasonable to ask whether acamprosate (calcium acetylhomotaurine; Campral), also FDA approved for the treatment of alcoholism, can be used effectively to treat PG. Acamprosate is not an opioid antagonist; rather, it is assumed that its therapeutic effects are due to actions on GABA receptors. Acamprosate is structurally related to 1-glutamic, which is an excitatory neurotransmitter. It has been proposed that acamprosate decreases the effects of the naturally-occuring excitatory neurotransmitter glutamate in the body. Because chronic alcohol consumption disrupts this system, and the changes last many months after alcohol ingestion is stopped, it is possible that acamprosate restores the glutamate system towards normal. Regardless, acamprosate decreases the pleasant "high" associated with alcohol consumption, and thus decreases the frequency of relapse during abstinence. We hypothesize that acamprosate will have similar actions in persons with PG.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label, Flexible Dose 12-Week Clinical Trial of the Safety and Efficacy of Acamprosate in the Treatment of Pathological Gambling
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Open Label Open Label. At visit 2, all participants were started on Acamprosate, 1,998 mg divided into 3 equal doses.	Drug: acamprosate; Two 333mg tablets taken three times daily.; Other Names: Campral

Outcome Measures

Primary Outcome Measures

1. The Primary Efficacy Measure Was the Yale-Brown Obsessive Compulsive Scale Modified for PG (YBOCS-PG). [8 weeks minus baseline]

   The YBOCS-PG (Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling) is used to assess the range and severity of PG symptoms. The scale is a modification of the YBOCS originally developed by Goodman et al. (1989) for use in rating severity and change in subjects with Obsessive Compulsive Disorder. This adaptation is a 10-item clinician-rated questionnaire, which rates (on a 5-point scale from 0 to 4) time spent, distress, interference, resistance, and control in relation to PG urges and behaviors. The scale ranges from 0 to 40 with a higher score representing increased severity in PG.

Secondary Outcome Measures

1. The Secondary Efficacy Evaluations Will Include the G-SAS (Gambling Symptom Assessment Scale), Clinical Global Impression - Improvement Scale (CGI-I) , and the CGI-S Clinical Global Impression - Severity Scale. [8 weeks minus baseline]

   The G-SAS is a 12 item self-report instrument that reflects the subjects urges to gamble and the subjects gambling behavior. Each item is scored on a 5-point scale from 0 (no symptoms) to 4 (extreme symptoms) with a total score range from 0 to 48. The CGI-I is a 7 point scale requiring the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. A patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; and 7, among the most extremely ill patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patients will meet DSM-IV (Diagnostic and Statistical Manual 4th Edition) criteria for Pathological Gambling Disorder

• Patients will achieve a SOGS (South Oaks Gambling Screen) score greater than or equal to 5

• Patients will be 18 years old or older

• Patients will speak standard English

• Patients will be able to give written Informed Consent

• Patients will be able to understand and cooperate with study procedures

Exclusion Criteria:

• Patients having a current (past 3 months) substance use disorder (except dependence)

• Patients having a Hamilton Depression Rating score of greater than or equal to 18 or a score on #1 (depressed mood) greater than 1.

• Patients having a clinically significant medical illness

• Patients at risk for aggressive or suicidal behavior

• Patients who have received the following interventions within the proscribed time prior to study entry: 1) a monoamine oxidase inhibitor within the previous 21 days; 2) long-acting phenothiazines within the previous 3 months; 3) other psychotropic drugs within the previous 14 days; 4) flu- oxetine within the previous 4 weeks.

• Patients having severe antisocial or borderline personality disorder

• Patients with a past or current diagnosis of schizophrenia, schizoaffective disorder, psychotic disorder, bipolar disorder, or delirium, dementia, or other clinically significant cognitive disorder.

• Patients initiating individual, group, or couple psychotherapy during the three moths prior to study entry (excluding Gambler's Anonymous)

• Patients having prior exposure to acamprosate

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Iowa
• University of Nebraska
• Forest Laboratories

Investigators

• Principal Investigator: Donald W Black, MD, The University of Iowa Carver College of Medicine
• Principal Investigator: Dennis P McNeilly, PsyD, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Donald Black, Principal Investigator, University of Iowa
• ClinicalTrials.gov Identifier: NCT00571103
• Other Study ID Numbers: 200608747
• First Posted: Dec 11, 2007
• Last Update Posted: May 25, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Donald Black, Principal Investigator, University of Iowa: acamprosate, impulse-control disorders
• Additional relevant MeSH terms: Gambling; Acamprosate

Study Results

Participant Flow

Recruitment Details	Subjects were recruited through newspaper advertising, word of mouth, and lab registries. Subjects were seen in each doctor's clinic respectively.
Pre-assignment Detail	Two subjects failed to meet study criteria (their severity of gambling was too low)and 6 subjects were lost to follow-up after the screening visit (Visit One).

Arm/Group Title	Open Label
Arm/Group Description	All subjects received the drug.
Period Title: Overall Study
STARTED	28
COMPLETED	26
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Open Label
Arm/Group Description	All subjects received the drug.
Overall Participants	28
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.0 (16.4)
Sex: Female, Male (Count of Participants)
Female	16 57.1%
Male	12 42.9%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Secondary Outcome

Title	The Secondary Efficacy Evaluations Will Include the G-SAS (Gambling Symptom Assessment Scale), Clinical Global Impression - Improvement Scale (CGI-I) , and the CGI-S Clinical Global Impression - Severity Scale.
Description	The G-SAS is a 12 item self-report instrument that reflects the subjects urges to gamble and the subjects gambling behavior. Each item is scored on a 5-point scale from 0 (no symptoms) to 4 (extreme symptoms) with a total score range from 0 to 48. The CGI-I is a 7 point scale requiring the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment. A patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; and 7, among the most extremely ill patients.
Time Frame	8 weeks minus baseline

Outcome Measure Data

Analysis Population Description

A total of 39 participants were screened by phone and 5 failed to meet screening criteria and were excluded; 6 did not return for the baseline visit because of follow-up loss or choosing to discontinue participation. of the remaining 28 patients, 1 discontinued and another was lost to follow-up after the baseline visit. That left 26 subjects.

Arm/Group Title	Open Label
Arm/Group Description	All subjects received the drug.
Measure Participants	26
G-SAS	-1.117 (.228)
CGI-I	-.145 (.031)
CGI-S	-.199 (.035)

2. Primary Outcome

Title	The Primary Efficacy Measure Was the Yale-Brown Obsessive Compulsive Scale Modified for PG (YBOCS-PG).
Description	The YBOCS-PG (Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling) is used to assess the range and severity of PG symptoms. The scale is a modification of the YBOCS originally developed by Goodman et al. (1989) for use in rating severity and change in subjects with Obsessive Compulsive Disorder. This adaptation is a 10-item clinician-rated questionnaire, which rates (on a 5-point scale from 0 to 4) time spent, distress, interference, resistance, and control in relation to PG urges and behaviors. The scale ranges from 0 to 40 with a higher score representing increased severity in PG.
Time Frame	8 weeks minus baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label
Arm/Group Description	All subjects received the drug.
Measure Participants	26
Mean (Standard Error) [units on a scale]	-.985 (.158)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open Label
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Linear mixed effects
	Comments
Method of Estimation	Estimation Parameter	Mean Slope
	Estimated Value	-.985
	Confidence Interval	(2-Sided) 95%; -1 to 1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .158
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected for eight weeks.
Arm/Group Title	Open Label
Arm/Group Description	All subjects received the drug.
All Cause Mortality
	Open Label
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Other (Not Including Serious) Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	0/28 (0%)

Limitations/Caveats

The sample was relatively small, and there was no comparison group; therefore, our results could have resulted from the placebo effect. Another limitation is the relatively short length of the trial. Furthermore, there were few minority subjects.

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.