Clinical trial NCT01811940
Conditions: Cocaine Dependence
Keywords: cocaine dependence adderall topiramate
Sponsor: New York State Psychiatric Institute
Start date: 2013-07-01; Completion date: 2017-06-01
Enrollment: 169 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The proposed protocol is a multi-site double-blind, placebo-controlled outpatient study of the safety and efficacy of Adderall-XR (MAS-ER) and topiramate in the treatment of cocaine dependence. 198 patients will be enrolled and 176 patients randomized in a 14-week trial. The proportion of participants achieving sustained cocaine abstinence for three consecutive weeks at the end of the study will be significantly greater for the combined pharmacotherapies group compared to the placebo group.

Detailed description:
The investigators hypothesize that the combination of an agent that increased baseline dopamine signaling (amphetamine) with one that reduced cocaine-induced dopamine release (topiramate) will improve dopamine regulation and be associated with improved cocaine use outcomes. 99 subjects at each of the two sites whom meet criteria for cocaine dependence, and all other study inclusion and exclusion criteria will be assigned to the 14-week double-blind, placebo-controlled treatment trial. Subjects will be randomized to receive either placebo or MAS-ER and topiramate. This proposal will test the hypothesis that MAS-ER and topiramate will promote cocaine abstinence. Participants who are randomized to the combination medication arm will have their dose titrated to 60 mg MAS-ER daily (over 2 weeks) and 200 mg topiramate a day (over 6 weeks) and maintained on this dose through week 13 of the trial. During week 14, participants will be tapered off both medications. All participants will receive a supportive behavioral treatment that emphasizes study procedure adherence. Starting in week one, all patients will receive incentives for compliance with study procedures on an escalating reinforcement schedule similar to that developed previously and not contingent on urine results. The purpose of the lead-out is to blind patients to the exact point of medication discontinuation and to provide naturalistic data on the effects of medication discontinuation. Moreover, a 3 month follow-up will be conducted to determine what happens to cocaine use after treatment discontinuation.

Arms: arm 1: Adderall-ER will be taken once per day in the morning or early afternoon since it may be activating. The dose is titrated to 60 mg per day or the maximum tolerated dose over two weeks and maintained for the duration of the study. Topiramate will be taken twice per day in the morning and the evening and titrated to 200mg/day or the maximum tolerated dose over the course of 6 weeks and maintained for the duration of the study. arm 2: Placebo will be packaged in matching gelatin capsules similar to the pills in the active arm. Placebo will be taken as frequently and for the same duration as those taken in the active arm.
Interventions: intervention 1: Adderall-ER intervention 2: Topiramate intervention 3: Placebo
Intervention descriptions: intervention 1: MAS-ER 60mg/day intervention 2: Topiramate 100 mg bid. intervention 3: Placebo

Protocol documents:
Prot_000.pdf: 































































SAP_001.pdf: 
 
 
Frances R. Levin   1 
 
Title Page: 
 
Grant: Multicenter Trial of Combined Pharmacotherapy to Treat Cocaine Dependence   
IRB# 6698 
 
PI: Frances R. Levin M.D.1,2 
 
1. New York State Psychiatric Institute, Division of Substance Abuse1  
1051 Riverside Drive 
New York, NY 10032 
USA 
 
2. Department of Psychiatry, College of Physicians and Surgeons of Columbia University2 
630 West 168th Street 
New York, NY 10032 
USA 
 
 
Data Analysis created on January 1, 2018 
 
Funding Source: Funding for this work was provided by NIDA. 
 
Trial Registration: clinicaltrials.gov Identifier:  NCT01811940 
 
 
 
 
 
 
 
 
 
 


 
 
Frances R. Levin   2 
 
Data Analysis 
The primary outcome was a dichotomous measure of a clinically meaningful treatment 
response, defined as three consecutive weeks of abstinence (no cocaine use based on self-
report confirmed by urine toxicology) at the end of the 12-week medication phase of the trial. 
Secondary outcomes were (1) dichotomous measure of at least 3 consecutive weeks of 
abstinence during the study, (2) dichotomous longitudinal, weekly status of cocaine use 
determined by urine toxicology samples per subject, positive status occurs if at least one urine 
sample was positive for benzoylecgonine, (3) continuous longitudinal, symptoms of cocaine 
withdrawal as measured by the Cocaine Selective Severity Assessment (CSSA) assessed at 
week 6,10, and 14, (4) continuous longitudinal, weekly cocaine cravings as measured by the 
Brief Substance Craving Scale (BSCS), and (5) survival, time to dropout.  
The dichotomous primary and secondary outcome (1) was analyzed using either exact or 
conventional logistic regressions with predictor treatment (MAS-ER and topiramate vs. placebo), 
and covariates: site (binary, UPENN vs. CUMC) and baseline severity of cocaine use 
(continuous, total number of cocaine use days in the 28 days prior to randomization). Secondary 
outcomes (2) – (4) were analyzed using longitudinal mixed effect models with logit link function 
for binary outcomes and linear link functions for continuous outcomes. Times to dropout (5) 
were compared using Kaplan-Meier curves and log-rank statistics.  
All analyses were conducted in SAS® and on the intent-to-treat sample of all randomized 
patients. All statistical tests were 2-tailed at a significance level of 5%, unless otherwise stated.