Glutamatergic Modulation of Cocaine-related Deficits

April 16, 2019 updated by: Elias Dakwar, New York State Psychiatric Institute

The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users

Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits. Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators, studies with human subjects have been unsuccessful to date. The purpose of this investigation is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting cocaine in cocaine dependent participants, 24-hours post-infusion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this study, volunteers will undergo a 9 day inpatient trial during which they will receive three counter-balanced infusions (two doses of ketamine and a dose of lorazepam) on three separate days in a within-subject, double-blind, controlled design. Of the various glutamate antagonists available for human use, ketamine will be utilized because its safety profile, pharmacokinetics, and range of tolerable sub-anesthetic dosings have been very well studied. Also, ketamine has shown promise in managing opiate and alcohol use disorders in certain studies, and may therefore be the most likely glutamate antagonist to dampen cue reactivity and increase motivation in cocaine users. If ketamine significantly improves these deficits, this would suggest that the drug should be investigated further for potential utility as a treatment for cocaine dependence.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • NYSPI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 52 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Active free-base cocaine dependence (at least 4 days of use over the past month, with at least 1 use per week); if the participant uses through another route (IN, IV), then the FB route is dominant (> 80% of occasions).
  2. Physically healthy
  3. No adverse reactions to study medications
  4. 21-52 years of age
  5. Normal body weight
  6. Responsive to drug cues
  7. Capacity to consent

Exclusion Criteria:

  1. Seeking treatment or abstinence
  2. DSM IV criteria for substance dependence (other than methamphetamine, cocaine, cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam
  3. DSM-IV criteria for other Axis I psychiatric illness that may make participation hazardous such as schizophrenia, schizoaffective disorder, psychosis NOS, MDD, psychosis secondary to substances, or bipolar disorder
  4. Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
  5. Current suicide risk or a history of suicide attempt within the past 2 years
  6. Current use of prescribed psychotropic medication
  7. Pregnancy, nursing, or had a baby within the past 6 mo.
  8. Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
  9. Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), anemia, active hepatitis or other liver disease, or diabetes
  10. "Bad" reaction/experience with prior exposure to ketamine or lorazepam
  11. History of significant violence
  12. First degree relative with a psychotic disorder

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: K1
Ketamine 0.41 mg/kg infused over 52 min (K1)
Drug: Ketamine 0.41 mg/kg
52 minute iv infusion of ketamine 0.41 mg/kg
Other Names:
  • K1
Experimental: K2
Ketamine 0.71 mg/kg infused over 52 min (K2)
Drug: Ketamine 0.71 mg/kg
52 minute iv infusion of ketamine 0.71 mg/kg. This dose follows K1 in all 3 orderings.
Other Names:
  • K2
Experimental: LZP
Lorazepam 2 mg infused over 52 minutes (LZP)
Drug: Lorazepam 2 mg
52 minute infusion of lorazepam 2 mg. This serves as an active control.
Other Names:
  • LZP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cue Reactivity
Time Frame: Baseline and 24 hours after infusion
Serial visual analogue scale (VAS) scores for craving elicited by cocaine cue: units on a scale (0-200), high is worse. Scores are obtained at baseline and at 24 hours after the infusion.
Baseline and 24 hours after infusion
Change in Motivation to Quit
Time Frame: Baseline and 24 hours post-infusion
Motivation score obtained from the University of Rhode Island Change Assessment (URICA). Scores are obtained at baseline and at 24 hours after each infusion. The scores are 0-13, with higher scores indicating greater motivation. The analysis is within-subject. Scores included below are means; higher scores represent higher motivation to quit than do lower scores.
Baseline and 24 hours post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Investigators

  • Principal Investigator: Elias Dakwar, MD, NYSPI/Columbia College of Physicians and Surgeons
  • Study Chair: Carl Hart, PhD, NYSPI/Columbia College of Physicians and Surgeons

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

February 8, 2013

First Submitted That Met QC Criteria

February 11, 2013

First Posted (Estimate)

February 13, 2013

Study Record Updates

Last Update Posted (Actual)

April 30, 2019

Last Update Submitted That Met QC Criteria

April 16, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #6162

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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