Glutamatergic Modulation of Cocaine-related Deficits

NCT01790490 | Completed Phase 2 Results DMC

• 1 other identifier: #6162
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and 24 hours after 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.

  Baseline and 24 hours post-infusion

Study Arms (3)

K1

EXPERIMENTAL

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

Drug: Ketamine 0.41 mg/kg

K2

EXPERIMENTAL

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

Drug: Ketamine 0.71 mg/kg

LZP

EXPERIMENTAL

Lorazepam 2 mg infused over 52 minutes (LZP)

Drug: Lorazepam 2 mg

Interventions

Ketamine 0.41 mg/kg DRUG

52 minute iv infusion of ketamine 0.41 mg/kg

Also known as: K1

K1

Ketamine 0.71 mg/kg DRUG

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

Also known as: K2

K2

Lorazepam 2 mg DRUG

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

Also known as: LZP

LZP

Eligibility Criteria

• Age: 21 Years - 52 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• years of age
• Normal body weight
• Responsive to drug cues
• Capacity to consent

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

NYSPI

New York, New York, 10032, United States

Location

Related Publications (1)

• 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.

  PMID: 24035344 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Ketamine; Lorazepam

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Elias Dakwar, MD
• Organization: NYSPI

dakware@nyspi.columbia.edu

(646) 774-8728

Study Officials

• Elias Dakwar, MD

  NYSPI/Columbia College of Physicians and Surgeons

  PRINCIPAL INVESTIGATOR

• Carl Hart, PhD

  NYSPI/Columbia College of Physicians and Surgeons

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Clinical Psychiatry

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 13, 2013
• Study Start: February 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 30, 2019
• Results First Posted: June 27, 2016

Record last verified: 2019-04

Locations

US (1)