The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence

Phase 1

Terminated

Conditions: Cocaine Dependence

Interventions: Drug: Ketamine
Drug: Midazolam

Registration Number: NCT01535937

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: This project will evaluate the effect of a single sub-anesthetic dose of ketamine on the time to first cocaine use and abstinence rates in 60 treatment-seeking cocaine-dependent individuals receiving mindfulness-based relapse prevention (MBRP) therapy, using a 5 week combined laboratory-inpatient and outpatient double-blind, randomized, controlled trial.

Detailed Description: he study will begin with an inpatient phase (phase 1) of 5 days, during which abstinence is achieved, followed by a 4 week outpatient phase (phase 2). A single infusion of ketamine or midazolam will occur on day 3 of Phase 1. In addition to measures of mindfulness and impulsivity, stress sensitivity tests are incorporated into the design in order to elucidate mechanisms of action. The study hypotheses are:

1. ketamine and MBRP will significantly increase the time to first use compared to placebo and MBRP in cocaine-dependent individuals.

2. ketamine and MBRP is significantly more likely to lead to abstinence from cocaine (no use over one week) as compared to placebo and MBRP.

3. ketamine and MBRP will significantly reduce subjective, endocrine, and physiological responses to stress (including cue exposure) as compared to placebo and MBRP.

4. ketamine and MBRP will significantly increase mindfulness, as assessed by the Five Facet Mindfulness Questionnaire (FFMQ), as compared to placebo and MBRP.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 55

Inclusion Criteria

Active cocaine dependence with at least 8 days of use or at least 4 binges of large amounts (>$200/occasion) over the past 30 days, and displaying at least one positive utox during screening
Physically healthy
No adverse reactions to study medications
21-60 years of age
Capacity to consent and comply with study procedures, including sufficient proficiency in English
Seeking treatment

Exclusion Criteria

Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance induced psychosis, and current substance-induced mood disorder with HAMD score > 12.
Physiological dependence on another substance requiring medical management, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis
Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders
Current suicide risk or a history of suicide attempt within the past year
Pregnant or interested in becoming pregnant during the study period
Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), WBC < 3.5, active hepatitis or other liver disease with elevated transaminase levels (< 2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creatinine > 2, BUN >40), or untreated diabetes
Previous history of ketamine or benzodiazepine misuse or abuse, and a history of an adverse reaction/experience with prior exposure to ketamine or benzodiazepine
Recent history of significant violence (past 2 years)
First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
BMI > 32, or a history of documented obstructive sleep apnea
On psychotropic or other medications whose effect could be disrupted by participation in the study
Patients who cannot comply with study procedures during the initial hospitalization phase

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine	Ketamine	0.5 mg/kg of ketamine IV over 40 minutes
midazolam	Midazolam	0.025 mg/kg IV over 40 minutes

Primary Outcome Measures

Name	Time	Method
Abstinence	Abstinence will be assessed over 4 weeks starting at the last day of week 1 and continuing through the end of study at the last day of week 5	Abstinence is defined as 2 or greater weeks of no cocaine use, as ascertained by the TLFB and urine toxicology.
Number of Participants With Cocaine Use/Drop Out	Over the four week period following discharge from the inpatient unit at Day 5	Number of participants who use cocaine and drop from study. During phase 2, patients will be assessed twice weekly by TLFB and urine toxicology for cocaine use. The day of first use will determine the length of time that transpired from discharge to the first lapse onto cocaine.

Secondary Outcome Measures