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Glutamatergic Modulation of Cocaine-related Deficits

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ClinicalTrials.gov Identifier: NCT01790490
Recruitment Status : Completed
First Posted : February 13, 2013
Results First Posted : June 27, 2016
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Elias Dakwar, New York State Psychiatric Institute

Tracking Information
First Submitted Date  ICMJE February 8, 2013
First Posted Date  ICMJE February 13, 2013
Results First Submitted Date  ICMJE October 31, 2013
Results First Posted Date  ICMJE June 27, 2016
Last Update Posted Date April 30, 2019
Study Start Date  ICMJE February 2011
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2016)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • Change in Cue Reactivity [ Time Frame: change across infusions over 9 days ]
    Serial visual analogue scale (VAS) scores for craving elicited by cocaine cue. Scores are obtained at baseline and at 24 hours after each infusion.
  • Change in Motivation [ Time Frame: Change across infusions over 9 days ]
    Motivation score obtained from the University of Rhode Island Change Assessment (URICA). Scores are obtained at baseline and at 24 hours after each infusion.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • Acute Tolerability [ Time Frame: immediately after each infusion over 5 days ]
    Various measures ascertain level of dissociation, abuse liability, and behavioral disturbances.
  • Risk of Initiating Experimental Drug Misuse [ Time Frame: 4 week follow-up after completion of inpatient phase ]
    Weekly assessment of drug use by history and urine toxicology
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 11, 2013)
  • Change in Physiological Reactivity [ Time Frame: change across infusions over 9 days ]
    Assesses level of physiological arousal to cues using galvanic skin response
  • Cocaine Use in Follow-up [ Time Frame: 4-week follow up ]
    Weekly assessment of cocaine use by urine toxicology and history
 
Descriptive Information
Brief Title  ICMJE Glutamatergic Modulation of Cocaine-related Deficits
Official Title  ICMJE The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cocaine Dependence
Intervention  ICMJE
  • Drug: Ketamine 0.41 mg/kg
    52 minute iv infusion of ketamine 0.41 mg/kg
    Other Name: K1
  • 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 Name: K2
  • Drug: Lorazepam 2 mg
    52 minute infusion of lorazepam 2 mg. This serves as an active control.
    Other Name: LZP
Study Arms  ICMJE
  • Experimental: K1
    Ketamine 0.41 mg/kg infused over 52 min (K1)
    Intervention: Drug: Ketamine 0.41 mg/kg
  • Experimental: K2
    Ketamine 0.71 mg/kg infused over 52 min (K2)
    Intervention: Drug: Ketamine 0.71 mg/kg
  • Experimental: LZP
    Lorazepam 2 mg infused over 52 minutes (LZP)
    Intervention: Drug: Lorazepam 2 mg
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 11, 2013)
8
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 52 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01790490
Other Study ID Numbers  ICMJE #6162
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Elias Dakwar, New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elias Dakwar, MD NYSPI/Columbia College of Physicians and Surgeons
Study Chair: Carl Hart, PhD NYSPI/Columbia College of Physicians and Surgeons
PRS Account New York State Psychiatric Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP