The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence

NCT ID: NCT01535937

Last Updated: 2019-05-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2017-04-30

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.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

0.5 mg/kg of ketamine IV over 40 minutes

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

0.5 mg/kg IV over 40 minutes

midazolam

0.025 mg/kg IV over 40 minutes

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

0.025 mg/kg IV over 40 minutes

Interventions

Ketamine

0.5 mg/kg IV over 40 minutes

Intervention Type: DRUG

Midazolam

0.025 mg/kg IV over 40 minutes

Intervention Type: DRUG

Other Intervention Names

ketamine 0.5 mg/kg; midazolam 0.025 mg/kg

Eligibility 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
• Patients who cannot comply with study procedures during the initial hospitalization phase

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Elias Dakwar

Assistant Professor of Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Herbert Kleber, M.D.

Role: STUDY_CHAIR

NYSPI

Elias Dakwar, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

References

Dakwar E, Nunes EV, Hart CL, Foltin RW, Mathew SJ, Carpenter KM, Choi CJJ, Basaraba CN, Pavlicova M, Levin FR. A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. Am J Psychiatry. 2019 Nov 1;176(11):923-930. doi: 10.1176/appi.ajp.2019.18101123. Epub 2019 Jun 24.

Reference Type: DERIVED

PMID: 31230464 (View on PubMed)

Other Identifiers

1K23DA031771-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

#6403/7339R

Identifier Type: -

Identifier Source: org_study_id