Trial Outcomes & Findings for Topiramate in the Treatment of Pathological Gambling (NCT NCT00245583)

NCT ID: NCT00245583

Last Updated: 2019-07-02

Results Overview

The obsessions subscale of the Yale-Brown Obsessive Compulsive Scale modified for PG (PG-YBOCS) measures the severity and change in severity of PG symptoms such as thoughts/urges and behaviors and has been shown to be reliable and valid and correlate with global severity and South Oaks Gambling Screen scores. The scale is a clinician-rated, each item rated from 0 (no symptoms) to 4 (extreme symptoms), Each component, Obsession and Compulsion, score ranges from 0-20, yielding a total possible score range from 0 to 40, with higher score indicating more symptoms.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 42 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2019-07-02

Participant Flow

Subjects were recruited primarily through community advertisements such as newspapers and targeted advertisements in casinos. Eligible participants were enrolled between October 26, 2005 and May 23, 2008.

Subjects were randomized in a 1:1 ratio to topiramate or placebo treatment. Following the baseline visit, participants underwent a 6-week titration period to 300mg/day or the maximum tolerated dose, followed by an 8-week maintenance. At the conclusion of the 14-weeks, study medication was tapered over a 7-day period.

Participant milestones

Measure	Topiramate 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo placebo equivalent tablets Placebo: matching tablet
Overall Study STARTED	20	22
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Measure	Topiramate 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo placebo equivalent tablets Placebo: matching tablet
Overall Study Lost to Follow-up	1	5
Overall Study Adverse Event	2	1
Overall Study Lack of Efficacy	1	0
Overall Study Withdrawal by Subject	2	3

Baseline Characteristics

Topiramate in the Treatment of Pathological Gambling

Baseline characteristics by cohort

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet	Total n=42 Participants Total of all reporting groups
Age, Continuous	50.45 years STANDARD_DEVIATION 10.44 • n=5 Participants	44.91 years STANDARD_DEVIATION 8.01 • n=7 Participants	47.5 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	15 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Smoking Smoker	8 participants n=5 Participants	15 participants n=7 Participants	23 participants n=5 Participants
Smoking Non-smoker	12 participants n=5 Participants	7 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

The obsessions subscale of the Yale-Brown Obsessive Compulsive Scale modified for PG (PG-YBOCS) measures the severity and change in severity of PG symptoms such as thoughts/urges and behaviors and has been shown to be reliable and valid and correlate with global severity and South Oaks Gambling Screen scores. The scale is a clinician-rated, each item rated from 0 (no symptoms) to 4 (extreme symptoms), Each component, Obsession and Compulsion, score ranges from 0-20, yielding a total possible score range from 0 to 40, with higher score indicating more symptoms.

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Obsessions	12.65 score on a scale Standard Deviation 2.08	12.95 score on a scale Standard Deviation 2.24
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Compulsions	11.10 score on a scale Standard Deviation 23.75	12.27 score on a scale Standard Deviation 2.91
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Total	23.75 score on a scale Standard Deviation 4.80	25.23 score on a scale Standard Deviation 4.89

PRIMARY outcome

Timeframe: 14 weeks

The obsessions subscale of the Yale-Brown Obsessive Compulsive Scale modified for PG (PG-YBOCS) measures the severity and change in severity of PG symptoms such as thoughts/urges and behaviors and has been shown to be reliable and valid and correlate with global severity and South Oaks Gambling Screen scores. The scale is a clinician-rated, each item rated from 0 (no symptoms) to 4 (extreme symptoms), Each component, Obsession and Compulsion, score ranges from 0-20, yielding a total possible score range from 0 to 40, with higher score indicating more symptoms.

Outcome measures

Measure	Topiramate n=14 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=13 Participants placebo equivalent tablets Placebo: matching tablet
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Obsessions	6.17 score on a scale Standard Deviation 3.28	7.62 score on a scale Standard Deviation 3.66
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Compulsions	5.28 score on a scale Standard Deviation 4.71	6.92 score on a scale Standard Deviation 4.48
Obsession Component of the Yale-Brown Obsessive-Compulsive Scale for Pathological Gambling (PG-YBOCS) Total	11.44 score on a scale Standard Deviation 7.81	14.54 score on a scale Standard Deviation 7.79

SECONDARY outcome

Timeframe: baseline and 14 weeks

Population: those who returned for week 14 visit included in data results

The Gambling-Symptom Assessment Scale (G-SAS) is a 12-item self-rated measure that is designed to assess gambling symptom severity and change during treatment. Each item is scored on a 4 point scale from 0-4 with 0 meaning no symptoms and 4 meaning extreme symptoms. The total score is 0 - 48, with higher score indicating more gambling problem. Scores 7 and lower are considered normal behavior, 8-20 are considered a mild gambling problem, 21-30 are considered a moderate gambling problem, 31-40 are considered a severe gambling problem and 40-48 are considered an extreme gambling problem.

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
Gambling-Symptom Assessment Scale Total Score baseline	31.95 score on a scale Standard Deviation 7.41	35.73 score on a scale Standard Deviation 7.85
Gambling-Symptom Assessment Scale Total Score 14 weeks	19.94 score on a scale Standard Deviation 9.18	23.00 score on a scale Standard Deviation 11.55

SECONDARY outcome

Timeframe: baseline

The Barratt Impulsiveness Scale (BIS-11) is a questionnaire designed to assess the personality/behavioral construct of impulsiveness, composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Subscale attentional score 8-32, subscale motor score 11-44, subscale nonplanning score 11-44, with higher scores for each subscale indicating worse outcomes. Total score from 30-120, with higher score indicating more impulsive symptoms. Items are scored on a 4-point scale:

Rarely/Never = 1 Occasionally = 2 Often = 3 Almost Always/Always = 4 Total scores of 72+ = high impulsiveness Total scores between 52 and 71 = within normal limits for impulsiveness Total scores lower than 52 are representative of an individual that is either extremely over-controlled or who has not honestly completed the questionnaire

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
Barratt Impulsiveness Scale-11 Attentional	18.18 score on a scale Standard Deviation 4.03	18.00 score on a scale Standard Deviation 4.57
Barratt Impulsiveness Scale-11 Motor	25.35 score on a scale Standard Deviation 3.83	25.27 score on a scale Standard Deviation 4.86
Barratt Impulsiveness Scale-11 Non-planning	30.07 score on a scale Standard Deviation 3.91	28.90 score on a scale Standard Deviation 5.50
Barratt Impulsiveness Scale-11 Total	73.59 score on a scale Standard Deviation 9.22	72.16 score on a scale Standard Deviation 12.50

SECONDARY outcome

Timeframe: week 14

The Barratt Impulsiveness Scale (BIS-11) is a questionnaire designed to assess the personality/behavioral construct of impulsiveness, composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Subscale attentional score 8-32, subscale motor score 11-44, subscale nonplanning score 11-44, with higher scores for each subscale indicating worse outcomes. Total score from 30-120, with higher score indicating more impulsive symptoms. Items are scored on a 4-point scale:

Rarely/Never = 1 Occasionally = 2 Often = 3 Almost Always/Always = 4 Total scores of 72+ = high impulsiveness Total scores between 52 and 71 = within normal limits for impulsiveness Total scores lower than 52 are representative of an individual that is either extremely over-controlled or who has not honestly completed the questionnaire

Outcome measures

Measure	Topiramate n=14 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=13 Participants placebo equivalent tablets Placebo: matching tablet
Barratt Impulsiveness Scale-11 Attentional	16.83 score on a scale Standard Deviation 4.3	17.41 score on a scale Standard Deviation 5.13
Barratt Impulsiveness Scale-11 Motor	22.32 score on a scale Standard Deviation 3.37	23.85 score on a scale Standard Deviation 5.05
Barratt Impulsiveness Scale-11 Non-planning	29.00 score on a scale Standard Deviation 4.04	30.38 score on a scale Standard Deviation 6.10
Barratt Impulsiveness Scale-11 Total	68.14 score on a scale Standard Deviation 8.30	71.66 score on a scale Standard Deviation 14.54

SECONDARY outcome

Timeframe: baseline and week 14

Population: those who returned for week 14 visit included in data results

The YMRS is an 11-item scale used to assess the severity of mania and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. Additional information is based upon clinical observations made during the course of the clinical interview. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. YMRS total score varies between zero and 60, with higher score indicating more symptoms. A score of <= 12 indicates remission of symptoms.

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
Young Mania Rating Scale (YMRS) Baseline	3.85 score on a scale Standard Deviation 3.65	3.95 score on a scale Standard Deviation 3.84
Young Mania Rating Scale (YMRS) 14 weeks	2.61 score on a scale Standard Deviation 2.97	1.6154 score on a scale Standard Deviation 2.02

SECONDARY outcome

Timeframe: baseline and week 14

Population: those who returned for week 14 visit included in data results

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a psychological questionnaire used by clinicians to assess the severity of depression among patients who have a diagnosis of depression.

The MADRS depression test includes 10 items and uses a 0 to 6 severity scale. Total score from 0-60. Higher scores indicate increasing depressive symptoms.

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
Montgomery-Asberg Depression Rating Scale Baseline	8.70 score on a scale Standard Deviation 8.29	9.54 score on a scale Standard Deviation 6.62
Montgomery-Asberg Depression Rating Scale week 14	7.06 score on a scale Standard Deviation 8.54	4.69 score on a scale Standard Deviation 5.74

SECONDARY outcome

Timeframe: baseline and week 14

Population: those who returned for week 14 visit included in data results

Hamilton Anxiety Rating Scale (HARS) - It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Higher score indicates more symptoms.

Outcome measures

Measure	Topiramate n=20 Participants 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 Participants placebo equivalent tablets Placebo: matching tablet
The Hamilton Anxiety Rating Scale Baseline	6.35 score on a scale Standard Deviation 3.62	7.68 score on a scale Standard Deviation 5.25
The Hamilton Anxiety Rating Scale week 14	4.94 score on a scale Standard Deviation 5.22	5.31 score on a scale Standard Deviation 6.99

Adverse Events

Topiramate

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Topiramate n=20 participants at risk 25mg to 300mg daily dose Topiramate: minimum does of 50mg/day	Placebo n=22 participants at risk placebo equivalent tablets Placebo: matching tablet
General disorders Tiredness	5.0% 1/20	9.1% 2/22
General disorders Headache	10.0% 2/20	13.6% 3/22
Gastrointestinal disorders Nausea	15.0% 3/20	18.2% 4/22
Musculoskeletal and connective tissue disorders Shoulder Pain	5.0% 1/20	9.1% 2/22

Additional Information

Dr. Heather Berlin

Icahn School of Medicine at Mount Sinai

Phone: 212-241-4761

Email: heather.berlin@mssm.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place