TAP: Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01087736
• Collaborator: United States Department of Defense (U.S. Fed), US Department of Veterans Affairs (U.S. Fed)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The proposed project aims to:

1. Obtain a preliminary assessment of the efficacy of topiramate treatment in reducing alcohol use in veterans with Post Traumatic Stress Disorder (PTSD) and alcohol dependence;

2. Obtain preliminary assessments of safety/tolerability of topiramate in these patients;

3. Assess the feasibility of recruitment and retention for topiramate treatment in this comorbid population; and 4) to inform the design of a planned subsequent larger controlled trial of topiramate.

PRIMARY HYPOTHESIS: Topiramate treatment combined with Medical Management alcohol counseling will be associated with a significant decrease in percent drinking days from baseline to end of treatment.

SECONDARY HYPOTHESIS: There will be significantly less percent drinking days in the topiramate treatment group compared to the placebo group.

Condition or Disease	Intervention/Treatment	Phase
PTSD; Alcohol Abuse; Alcoholism	Drug: Topiramate; Other: Placebo administration	Phase 4

Detailed Description

The goal of the proposed project is to improve the treatment of veterans with co-occurring Post Traumatic Stress Disorder (PTSD) and alcohol dependence. Exposure to the stresses of combat is known to be associated with risk for both PTSD and alcohol and other substance use. PTSD and alcohol use disorders occur frequently among returning OEF/OIF veterans. Alcohol and substance use are risk factors for the development of PTSD, moderators of PTSD symptom severity, and potential consequences of PTSD. Alcohol is by far the most common substance of abuse in patients with PTSD, and its use may represent an attempt by PTSD patients to "self-medicate" symptoms such as hyperarousal. However, to date there has been little research to develop pharmacotherapies that would, ideally, reduce both alcohol use and PTSD symptoms.

Topiramate is one of the few medications for alcohol dependence that has also been tested as a potential medication to treat PTSD. Topiramate's efficacy in alcohol dependence has been shown in two recent large controlled trials. Several open trials have suggested that topiramate may be effective in reducing PTSD symptoms while the results of two small controlled trials have been mixed.

A clinical trial of topiramate is therefore indicated in order to achieve the following specific aims:

The primary aim is to obtain a preliminary assessment of the efficacy of topiramate in increasing the percent of days abstinent from alcohol use from baseline to the end of treatment in veterans with PTSD and alcohol abuse/dependence who are drinking heavily.

The secondary aim is to obtain a preliminary assessment of the efficacy of topiramate in increasing the percent of days abstinent from alcohol as compared to placebo.

Additional aims include the following:

• To obtain a preliminary assessment of the efficacy of topiramate in reducing other measures of alcohol use such as percent heavy drinking days, number of drinks per week, number of drinks per drinking day, and alcohol craving.

• To obtain a preliminary assessment of the efficacy of topiramate in reducing PTSD symptom severity in veterans with chronic PTSD and alcohol abuse/dependence.

• Informing the design of a planned subsequent larger controlled trial of topiramate in veterans with chronic PTSD and alcohol abuse/dependence

• To obtain an estimate of topiramate vs. placebo effect size for future studies. B. To obtain a preliminary assessment of the effects of topiramate treatment on measures of risk-taking behavior in veterans with chronic PTSD and alcohol abuse/dependence.

To achieve these aims, we will conduct a prospective, parallel groups, randomized, double-blind, placebo-controlled flexible-dose pilot clinical trial of topiramate in veterans with PTSD and alcohol abuse/dependence who are already receiving standard treatment for PTSD but still drink heavily. The primary treatment outcome will be percent days abstinent from alcohol; secondary outcomes will include other alcohol use measures, PTSD symptom severity, adverse effects, recruitment and retention rates.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topiramate Participants will be randomly assigned to either the topiramate arm or placebo arm. Neither the participant nor the researchers will know which arm the participant is in. Participants in the topiramate arm will be ingesting daily doses of topiramate that will gradually increase to a maximum, and then taper off.	Drug: Topiramate; After random assignment, topiramate will be titrated up over 5 weeks. Dosing begins at 25 mg per day, and increase in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Patients will receive the highest dose tolerated, not to exceed 300 mg per day. Adjustments are permitted throughout titration. Once maximum tolerated dosage is reached, subjects will be asked to maintain dosage for remainder of the treatment phase. Upon completing the 6 week maintenance period subjects will taper off over a 7-day period (Week 12). If subjects experience significant side effects, the dosage may be adjusted.; Other Names: Topamax Qnexa
Placebo Comparator: Placebo The Drug Product Services Laboratory at UCSF will purchase and supply our lab with USP or NF grade topiramate study capsules and matching placebo capsules. Randomization will be done by a consulting biostatistician, who will be the only one to know which participants are assigned to placebo. Dosing will follow the same procedures as with topiramate in that arm of the study. If adverse events occur, there will be a procedure in place for unblinding only that participant.	Other: Placebo administration; Placebo pills will be prepared by the UCSF pharmacy which will be indistinguishable from the topiramate pills used in that arm. Both topiramate and placebo will then be delivered to the VA pharmacy. A consulting biostatistician will randomly assign participants to either the topiramate or placebo group. The dosing of placebo pills will follow the same regimen as outlined for the topiramate arm. In the event of a safety issue, there will be a procedure for unblinding only that participant.; Other Names: Placebo Sugar pill

Outcome Measures

Primary Outcome Measures

1. Percent Drinking Days (%DD) [Weekly, weeks 1-12, average]

   Alcohol consumption was assessed at baseline and weekly during the treatment phase (12 weeks) using the Time Line Follow Back (TLFB) interview which yields number of days of alcohol use (DD). DD: day on which alcohol was consumed Standard alcoholic drink defined as containing 13.6 g of pure alcohol.

Other Outcome Measures

1. PTSD Symptom Severity [Weeks 4, 8, 12]

   The average PTSD symptom severity score during treatment (weeks 4, 8, 12). The PTSD Checklist (PCL) is a self-report measure of the 17 DSM-IV symptoms of PTSD. Respondents rate on a scale from 1 (not at all) to 5 (extremely) how much they were bothered by each symptom in the past month. A total symptom severity score (range = 17 - 85) can be obtained by summing the scores from the 17 items, with higher scores indicating greater severity of PTSD symptoms. Mean scores may be calculated for subscales of intrusion (range 5-25), avoidance (range 7-35), and arousal (range 5-25).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male and female outpatient veterans.

• Current DSM-IV diagnosis of PTSD.

• Current (past month) DSM-IV diagnosis of an Alcohol Use Disorder.

• Must meet criteria for "heavy" or "at-risk" drinking by NIAAA thresholds.

• Receiving treatment for PTSD.

• Must express desire to reduce alcohol consumption.

• Female subjects must have negative urine pregnancy test and must be either postmenopausal for at least one year, or practicing an effective method of birth control.

• Must have a BAC of less than 0.02% when signing the informed consent.

Exclusion Criteria:

• Psychotic disorders, bipolar disorder, dementia, or other psychiatric disorders judged to be unstable.

• Subjects known to have clinically significant unstable medical conditions, including but not limited to: clinically significant renal disease and/or impaired renal function as defined by clinically significant elevation of BUN or creatinine or an estimated creatinine clearance of < 60 mL/min; AST (SGOT) and/or ALT (SGPT) >3 times the upper limit of the normal range and/or an increased serum bilirubin >2 times the upper limit of normal; seizure disorders.

• Subjects with glaucoma.

• Subjects with a history of kidney stones.

• Subjects with a history of renal disease.

• Concurrent participation in another treatment study.

• Female patients who are pregnant or lactating.

• Current topiramate use or use within the past 4 weeks.

• Current medications for alcohol dependence or use within the past 4 weeks.

• Needing acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD);

• Subjects who are legally mandated to participate in an alcohol treatment program.

• Subjects who have had a suicide attempt or suicidal ideation in the 6 months prior to enrollment.

• Subjects who have previously been treated with topiramate for any reason and discontinued treatment due to an adverse event or due to a hypersensitivity reaction to topiramate,

• Subjects with seizure disorders that require anticonvulsant medications

• Subjects currently being treated with another anticonvulsant.

• Subjects who in the opinion of the investigator should not be enrolled in the study because of the precautions,warnings or contraindications outlined in the topiramate package insert.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco VA Medical Center	San Francisco	California	United States	94121

Sponsors and Collaborators

• University of California, San Francisco
• United States Department of Defense
• US Department of Veterans Affairs

Investigators

• Principal Investigator: Steven L. Batki, MD, University of California, San Francisco; Department of Veteran's Affairs

Study Documents (Full-Text)

None provided.

More Information

Publications

• Alderman CP, McCarthy LC, Condon JT, Marwood AC, Fuller JR. Topiramate in combat-related posttraumatic stress disorder. Ann Pharmacother. 2009 Apr;43(4):635-41. doi: 10.1345/aph.1L578. Epub 2009 Mar 31.
• Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995 Feb;19(1):92-9.
• Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17.
• Baker F, Johnson MW, Bickel WK. Delay discounting in current and never-before cigarette smokers: similarities and differences across commodity, sign, and magnitude. J Abnorm Psychol. 2003 Aug;112(3):382-92.
• Batki SL, Dimmock JA, Wade M, Gately PW, Cornell M, Maisto SA, Carey KB, Ploutz-Snyder R. Monitored naltrexone without counseling for alcohol abuse/dependence in schizophrenia-spectrum disorders. Am J Addict. 2007 Jul-Aug;16(4):253-9.
• Beckham JC, Crawford AL, Feldman ME. Trail making test performance in Vietnam combat veterans with and without posttraumatic stress disorder. J Trauma Stress. 1998 Oct;11(4):811-9.
• Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002 Jan;63(1):15-20.
• Berlant JL. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder. BMC Psychiatry. 2004 Aug 18;4:24.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01087736
• Other Study ID Numbers: H5220-34690-01; DAMD17-03-1-0532
• First Posted: Mar 16, 2010
• Last Update Posted: Jun 3, 2014
• Last Verified: May 1, 2014

• Keywords provided by University of California, San Francisco: PTSD; Alcohol abuse; Alcoholism; Topiramate; Stress Disorder, Post Traumatic; Chronic Post-Traumatic Stress Disorder
• Additional relevant MeSH terms: Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Topiramate

Study Results

Participant Flow

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Period Title: Overall Study
STARTED	14	16
COMPLETED	13	14
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Topiramate	Placebo	Total
Arm/Group Description	Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.	Total of all reporting groups
Overall Participants	14	16	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.5 (13.9)	50.4 (12.8)	50 (13.1)
Sex: Female, Male (Count of Participants)
Female	1 7.1%	1 6.3%	2 6.7%
Male	13 92.9%	15 93.8%	28 93.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 7.1%	0 0%	1 3.3%
Asian	1 7.1%	1 6.3%	2 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	1 6.3%	1 3.3%
Black or African American	2 14.3%	5 31.3%	7 23.3%
White	8 57.1%	8 50%	16 53.3%
More than one race	2 14.3%	1 6.3%	3 10%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	16 100%	30 100%
History of combat exposure (participants) [Number]
Combat exposure	10 71.4%	12 75%	22 73.3%
No combat exposure	4 28.6%	4 25%	8 26.7%
Comorbid substance use disorder (participants) [Number]
Comorbid substance use disorder present	5 35.7%	5 31.3%	10 33.3%
Comorbid substance use disorder absent	9 64.3%	11 68.8%	20 66.7%
Prior treatment for substance use disorder (participants) [Number]
Residential treatment	4 28.6%	2 12.5%	6 20%
Outpatient treatment	7 50%	8 50%	15 50%
No prior substance use disorder treatment	3 21.4%	6 37.5%	9 30%
BDI (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	23.4 (11.6)	26.3 (12.3)	24.9 (11.9)
BAI (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.4 (12.7)	27.4 (13.3)	24.0 (13.3)
Alcohol Use Disorders Identification Test (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.1 (7.9)	23.0 (7.5)	24.9 (7.8)
Percent drinking days per week (percent days in a week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent days in a week]	73.3 (30.3)	80.4 (21.5)	77.1 (25.8)
Percent heavy drinking days per week (percent days in a week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent days in a week]	58.5 (33.7)	72.6 (28.5)	66.0 (31.3)
Average drinks per week (Drinks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Drinks]	52.4 (34.2)	58.2 (25.4)	55.5 (29.4)
Average drinks per drinking day (Drinks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Drinks]	11.1 (6.1)	10.9 (4.7)	11.0 (5.3)
Baseline PTSD Symptomatology (units on a scale) [Mean (Standard Deviation) ]
PTSD total score	72.8 (14.3)	83.1 (17.3)	78.3 (16.6)
Intrusion subscale	18.2 (4.3)	21.9 (6.9)	20.2 (6.0)
Avoidance subscale	31.1 (6.1)	34.8 (8.9)	33.1 (7.8)
Arousal subscale	23.5 (6.7)	26.4 (4.1)	25.0 (5.6)

Outcome Measures

1. Primary Outcome

Title	Percent Drinking Days (%DD)
Description	Alcohol consumption was assessed at baseline and weekly during the treatment phase (12 weeks) using the Time Line Follow Back (TLFB) interview which yields number of days of alcohol use (DD). DD: day on which alcohol was consumed Standard alcoholic drink defined as containing 13.6 g of pure alcohol.
Time Frame	Weekly, weeks 1-12, average

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Measure Participants	14	16
Mean (Standard Deviation) [percent days in a week]	19.5 (34.2)	39.7 (36.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate
	Comments	Our primary protocol-defined analysis was to examine the within-group efficacy of topiramate to reduce percent drinking days (%DD).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	We tested our Primary hypothesis with a random-intercept repeated subject negative binomial model, modeling week (baseline - week 12) as a continuous variable. All analyses were intent-to-treat and used all observations from all weeks.
	Method	negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Incidence Rate Ratio (IRR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.89 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	There were no pre hoc hypothesis regarding change within placebo group. We were only tested change within the topiramate condition.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.00
	Comments
	Method	Other
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Topiramate, Placebo
	Comments	A secondary analysis was powered to detect a "Signal" or statistical trend (p<0.10) for a difference between the topiramate and placebo condition. We compared percent drinking days per week between groups averaged over the active phase of the trial (weeks 1-12). The negative binomial model included fixed effect for week, treatment group, and the interaction between treatment group and week. We covaried for baseline %DD averages to control for prestudy and study enrollment effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	Incidence Rate Ratio (IRR)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Other Pre-specified Outcome

Title	PTSD Symptom Severity
Description	The average PTSD symptom severity score during treatment (weeks 4, 8, 12). The PTSD Checklist (PCL) is a self-report measure of the 17 DSM-IV symptoms of PTSD. Respondents rate on a scale from 1 (not at all) to 5 (extremely) how much they were bothered by each symptom in the past month. A total symptom severity score (range = 17 - 85) can be obtained by summing the scores from the 17 items, with higher scores indicating greater severity of PTSD symptoms. Mean scores may be calculated for subscales of intrusion (range 5-25), avoidance (range 7-35), and arousal (range 5-25).
Time Frame	Weeks 4, 8, 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Measure Participants	14	16
PCL Total Score (Weeks 1-12 Average)	42.3 (16.4)	49.0 (16.5)
PCL-B Intrusion (Weeks 1-12 Average)	12.3 (5.5)	14.3 (5.5)
PCL-C Avoidance (Weeks 1-12 Average)	17.6 (7.4)	19.9 (6.9)
PCL-D Arousal (Weeks 1-12 Average)	12.4 (4.9)	14.9 (5.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topiramate
	Comments	We planned to explore the efficacy of topiramate in reducing PTSD symptom severity. We used random-intercept linear mixed models to explore the efficacy for topiramate related reduction in PTSD symptomatology. We looked for an effect of week within TOP. Baseline scores for PTSD symptoms were used as covariates in group comparisons. All analyses were intent-to-treat and used all observations from all weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.026
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	There was not a pre hoc hypothesis regarding change within placebo group. We only examined within group change in the topiramate condition.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.00
	Comments
	Method	Other
	Comments

Adverse Events

Time Frame	12 Weeks
Arm/Group Title	Topiramate		Placebo
Arm/Group Description	Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).		Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
All Cause Mortality
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		4/16 (25%)
Cardiac disorders
Chest pain	0/14 (0%)	0	2/16 (12.5%)	4
General disorders
Death	0/14 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Suicidal ideation	0/14 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/14 (85.7%)		13/16 (81.3%)
Eye disorders
Abnormal vision	3/14 (21.4%)	3	3/16 (18.8%)	3
Eye pain	1/14 (7.1%)	1	2/16 (12.5%)	2
Gastrointestinal disorders
Diarrhea	4/14 (28.6%)	4	3/16 (18.8%)	3
General disorders
Fatigue	3/14 (21.4%)	3	2/16 (12.5%)	2
Loss of appetite	4/14 (28.6%)	4	6/16 (37.5%)	6
Dizziness	1/14 (7.1%)	1	4/16 (25%)	4
Itching	3/14 (21.4%)	3	1/16 (6.3%)	1
Sleepiness	5/14 (35.7%)	5	2/16 (12.5%)	2
Nervous system disorders
numbness/tingling	3/14 (21.4%)	3	2/16 (12.5%)	2
Altered taste	3/14 (21.4%)	3	5/16 (31.3%)	5
Difficulty with concentration/attention	2/14 (14.3%)	2	1/16 (6.3%)	1
Difficulty with memory	1/14 (7.1%)	1	1/16 (6.3%)	1
Slow thinking	2/14 (14.3%)	2	2/16 (12.5%)	2
Confusion	2/14 (14.3%)	2	3/16 (18.8%)	3
Language problems	1/14 (7.1%)	1	1/16 (6.3%)	1
Psychiatric disorders
Nervousness	1/14 (7.1%)	1	1/16 (6.3%)	1
Depression	0/14 (0%)	0	1/16 (6.3%)	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.