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Glutamatergic Modulation of Cocaine-related Deficits

Primary Purpose

Cocaine Dependence

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ketamine 0.41 mg/kg

Ketamine 0.71 mg/kg

Lorazepam 2 mg

About this trial

This is an interventional treatment trial for Cocaine Dependence

Eligibility Criteria

21 Years - 52 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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).
Physically healthy
No adverse reactions to study medications
21-52 years of age
Normal body weight
Responsive to drug cues
Capacity to consent

Exclusion Criteria:

Seeking treatment or abstinence
DSM IV criteria for substance dependence (other than methamphetamine, cocaine, cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam
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
Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
Current suicide risk or a history of suicide attempt within the past 2 years
Current use of prescribed psychotropic medication
Pregnancy, nursing, or had a baby within the past 6 mo.
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), anemia, active hepatitis or other liver disease, or diabetes
"Bad" reaction/experience with prior exposure to ketamine or lorazepam
History of significant violence
First degree relative with a psychotic disorder

Sites / Locations

NYSPI

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

LZP

Arm Description

Ketamine 0.41 mg/kg infused over 52 min (K1)

Ketamine 0.71 mg/kg infused over 52 min (K2)

Lorazepam 2 mg infused over 52 minutes (LZP)

Outcomes

Primary Outcome Measures

Change in Cue Reactivity

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.

Change in Motivation to Quit

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01790490

First Posted

February 8, 2013

Last Updated

April 16, 2019

Sponsor

New York State Psychiatric Institute

1. Study Identification

Unique Protocol Identification Number

NCT01790490

Brief Title

Glutamatergic Modulation of Cocaine-related Deficits

Official Title

The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

New York State Psychiatric Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Dependence

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Ketamine 0.41 mg/kg infused over 52 min (K1)

Arm Title

Arm Type

Experimental

Arm Description

Ketamine 0.71 mg/kg infused over 52 min (K2)

Arm Title

LZP

Arm Type

Experimental

Arm Description

Lorazepam 2 mg infused over 52 minutes (LZP)

Intervention Type

Drug

Intervention Name(s)

Ketamine 0.41 mg/kg

Other Intervention Name(s)

Intervention Description

52 minute iv infusion of ketamine 0.41 mg/kg

Intervention Type

Drug

Intervention Name(s)

Ketamine 0.71 mg/kg

Other Intervention Name(s)

Intervention Description

52 minute iv infusion of ketamine 0.71 mg/kg. This dose follows K1 in all 3 orderings.

Intervention Type

Drug

Intervention Name(s)

Lorazepam 2 mg

Other Intervention Name(s)

LZP

Intervention Description

52 minute infusion of lorazepam 2 mg. This serves as an active control.

Primary Outcome Measure Information:

Title

Change in Cue Reactivity

Description

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.

Time Frame

Baseline and 24 hours after infusion

Title

Change in Motivation to Quit

Description

Time Frame

Baseline and 24 hours post-infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

52 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria 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). Physically healthy No adverse reactions to study medications 21-52 years of age Normal body weight Responsive to drug cues Capacity to consent Exclusion Criteria: Seeking treatment or abstinence DSM IV criteria for substance dependence (other than methamphetamine, cocaine, cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam 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 Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders Current suicide risk or a history of suicide attempt within the past 2 years Current use of prescribed psychotropic medication Pregnancy, nursing, or had a baby within the past 6 mo. 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), anemia, active hepatitis or other liver disease, or diabetes "Bad" reaction/experience with prior exposure to ketamine or lorazepam History of significant violence First degree relative with a psychotic disorder

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elias Dakwar, MD

Organizational Affiliation

NYSPI/Columbia College of Physicians and Surgeons

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Carl Hart, PhD

Organizational Affiliation

NYSPI/Columbia College of Physicians and Surgeons

Official's Role

Study Chair

Facility Information:

Facility Name

NYSPI

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24035344

Citation

Dakwar E, Levin F, Foltin RW, Nunes EV, Hart CL. The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers. Biol Psychiatry. 2014 Jul 1;76(1):40-6. doi: 10.1016/j.biopsych.2013.08.009. Epub 2013 Sep 12.

Results Reference

derived

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Glutamatergic Modulation of Cocaine-related Deficits

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