The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence - Full Text View

Purpose

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. The 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:

ketamine and MBRP will significantly increase the time to first use compared to placebo and MBRP in cocaine-dependent individuals.
ketamine and MBRP will significantly reduce subjective, endocrine, and physiological responses to stress (including cue exposure) as compared to placebo and MBRP.
ketamine and MBRP is significantly more likely to lead to abstinence from cocaine (no use over one week) as compared to placebo and MBRP.
ketamine and MBRP will significantly increase mindfulness, as assessed by the Five Facet Mindfulness Questionnaire (FFMQ), as compared to placebo and MBRP.

Condition	Intervention	Phase
Cocaine Dependence	Drug: Ketamine Drug: Midazolam (control)	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment

Resource links provided by NLM:

Drug Information available for: Ketamine hydrochloride Ketamine Midazolam hydrochloride

U.S. FDA Resources

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:

Time to first cocaine use [ Time Frame: Over the four week period following discharge from the inpatient unit at Day 5 ] [ Designated as safety issue: No ]
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:

Abstinence Rates [ Time Frame: 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 ] [ Designated as safety issue: No ]
Abstinence is defined as an average two weeks or greater of no cocaine use, as ascertained by TLFB and urine toxicology.
Stress and cue reactivity [ Time Frame: This will be assessed over the five week course of the trial; on days 1 and 5, on the last day of week 2, and on the last day of week 5 ] [ Designated as safety issue: No ]
Self-assessments as well as endocrine, physiological, and other assessments are used to ascertain stress and cue reactivity as well as craving at the above-mentioned time-points as well as, in some cases, continuously over the five week period of the trial.
Mindfulness [ Time Frame: This will be assessed over the five week course of the trial; on days 1 and 5, on the last day of week 2, and on the last day of week 5 ] [ Designated as safety issue: No ]
The Five Facet Mindfulness Questionnaire will be administered at various points throughout the study in order to ascertain the effect of the intervention on mindfulness as compared to the control.

Estimated Enrollment:	60
Study Start Date:	February 2012
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	September 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ketamine 0.5 mg/kg of ketamine IV over 40 minutes	Drug: Ketamine 0.5 mg/kg IV over 40 minutes
Active Comparator: midazolam 0.025 mg/kg IV over 40 minutes	Drug: Midazolam (control) 0.025 mg/kg IV over 40 minutes

Eligibility

Ages Eligible for Study:	21 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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
Patient serum Cortisol is less than 10 mcg/dL on admission testing for am testing, and less than 5 mcg/dL for pm testing.
Patients who cannot comply with study procedures during the initial hospitalization phase
Supplemental exclusion criteria for cold pressor test (CPT): history of frostbite, open cut or sore on foot to be immersed, history of Raynaud's disorder

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535937

Contacts

Contact: Elias Dakwar, M.D.

212.543.6709

dakware@nyspi.columbia.edu

Locations

United States, New York
New York State Psychiatric Institute	Recruiting
New York, New York, United States, 10032
Contact: Elias Dakwar, M.D.
Principal Investigator: Elias Dakwar, M.D.

Sponsors and Collaborators

New York State Psychiatric Institute

National Institute on Drug Abuse (NIDA)

Investigators

Study Chair:	Frances Levin, M.D.	NYSPI
Principal Investigator:	Elias Dakwar, MD	New York State Psychiatric Institute

More Information

No publications provided

Responsible Party:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT01535937 History of Changes
Other Study ID Numbers:	#6403, 1K23DA031771-01
Study First Received:	December 29, 2011
Last Updated:	December 4, 2012
Health Authority:	United States: Food and Drug Administration United States: Federal Government

Additional relevant MeSH terms:

Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Ketamine
Midazolam
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Hypnotics and Sedatives
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on May 22, 2013