Clinical trial NCT01531153: Cognitive Enhancement as a Target for Cocaine Pharmacotherapy
Official title: Cognitive Enhancement as a Target for Cocaine Pharmacotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Addiction
Keywords: Cocaine use decreases, increases or stays the same
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2012-02-10
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Specific Aim #1: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in reducing cocaine use as measured by cocaine urine results and self-report days of use.

Specific Aim # 2: To determine if galantamine (8 or 16 mg/day) is more effective than placebo in improving attention, assessed with the Rapid Visual Information Processing (RVIP) and the Simple Reaction Time (SRT) tests Specific Aim # 3: To determine if improvement in attention during the first four weeks of treatment will mediate galantamine's efficacy in reducing cocaine use.

Detailed description: This will be a double-blind, placebo-controlled, randomized clinical trial. One hundred and twenty cocaine-dependent men and women will be randomized to one of three treatment groups: placebo (n=40), 8 mg/day (n=40), and 16 mg/day (n=40) of extended release (ER) galantamine. An urn randomization will be used to balance the groups for gender, severity of cocaine use (measured by days of cocaine use), baseline cognitive functioning \[determined via the Shipley Institute of Living Scale (SILS)\], and smoking status. Gender and severity of cocaine use have been shown to predict treatment responses in cocaine users (76). Similarly, balancing the treatment groups for baseline cognitive functioning, assessed with the SILS scores, will minimize the influence of baseline differences on cognitive outcomes (77, 78). Smoking status is also an important baseline variable, given galantamine's actions on nicotinic receptors and its potential efficacy for smoking cessation (65). The initial dose of galantamine will be 8 mg/day as a single dose, as recommended for clinical use. For those assigned to 16 mg/day, the dose of galantamine will be increased to 16 mg at the end of week 4. Treatment groups will remain on their full dosage through week 13. All participants will receive contingency management (CM) targeting treatment compliance. In three previous cocaine pharmacotherapy trials using bupropion, desipramine or levodopa, medication efficacy on cocaine use was evident only when medications were combined with CM, but not with standard care (79-81). These findings provide a strong rationale for using CM in our clinical trial.

Recruitment is continuing. This protocol was amended as of May 2014 to come to one dispensing visit and up too, two clinic visits. The payment has changed from gift cards to cash. This change should help increase the number of completers.

Currently there are 40 completers with 9 active and 6 in follow up phase. The follow up phase ended June 2016. Currently in analysis.

Eligibility criteria: Inclusion Criteria:

1. Male and females, between the ages of 18 and 60
2. Are using cocaine more than once per week in the previous 30 days, provide a cocaine-positive urine specimen at screening, and fulfill criteria for current cocaine dependence according to DSM-IV
3. For women of child-bearing age, have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, and agree to have monthly pregnancy tests
4. Are fluent in English and have a 6th grade or higher reading level; AND
5. Can commit to at least 13 weeks of treatment and are willing to be randomized to treatment

Exclusion Criteria:

1. Meet DSM-IV psychiatric classifications for lifetime schizophrenia or bipolar disorder, or have a depressive or anxiety disorder with current use of a prescribed psychotropic medication that cannot be discontinued
2. Current DSM-IV diagnosis of drug or alcohol dependence (other than cocaine, or tobacco)
3. Demonstrate significant medical conditions, including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal deficit and cardiac rhythm disturbances or any other medical conditions that the study physician deems contraindicated for galantamine treatment
4. Use of other medications including:

   * drugs that slow heart rate (e.g., beta-blockers), which may increase the risk of bradycardia and atrioventricular (AV) block and
   * non-steroidal anti-inflammatory drugs (NSAIDs); increased potential for developing ulcers/active or occult gastrointestinal bleeding
5. Have a screening liver function test (AST or ALT) greater than 3 times normal; OR
6. Known allergy or adverse reaction to galantamine

Primary outcomes:
measure: Urine Toxicology
timeFrame: 12 weeks
Secondary outcomes:
measure: Heart Rate
timeFrame: once a day for up to two days over 12 Weeks
measure: Blood Pressure- Systolic
timeFrame: 2 times a week for 12 weeks
measure: Blood Pressure- Diastolic
timeFrame: 2 times a week for 12 weeks
measure: CANTAB RVIP Measure: RVP A
timeFrame: Baseline and 12 Weeks
measure: CANTAB RVIP Measure: RVP B
timeFrame: Baseline and 12 Weeks
measure: CANTAB RVIP Measure: RVP FALSE ALARM
timeFrame: Baseline and 12 Weeks
measure: CANTAB SST- SSRT
timeFrame: Baseline and 12 Weeks
measure: CANTAB SST- Median Correct
timeFrame: Baseline and 12 Weeks
measure: CANTAB SST- SD Correct
timeFrame: Baseline and 12 Weeks
measure: Stroop- RT Correct Neutral
timeFrame: weeks 0, 4, 8, 12, 16, 24, 36
measure: Stroop- RT Correct Drug
timeFrame: weeks 0, 4, 8, 12, 16, 24, 36
measure: Stroop- Effect Drug Neutral Mean Correct
timeFrame: weeks 0, 4, 8, 12, 16, 24, 36
measure: Digit Span- LDSF
timeFrame: Baseline and 12 Weeks
measure: Digit Span- DSF
timeFrame: Baseline and 12 Weeks
measure: Digit Span- LDSB
timeFrame: Baseline and 12 Weeks
measure: Digit Span- DSB
timeFrame: Baseline and 12 Weeks
Other outcomes:
Locations:
city: West Haven
country: United States
facility: Department of Veterans Affairs
state: Connecticut
Study officials:
affiliation: Yale University
name: Mehmet Sofuoglu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: