Glutamatergic Modulation of Cocaine-related Deficits

NCT ID: NCT01790490

Last Updated: 2019-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2012-03-31

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.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

K1

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

Group Type: EXPERIMENTAL

Ketamine 0.41 mg/kg

Intervention Type: DRUG

52 minute iv infusion of ketamine 0.41 mg/kg

K2

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

Group Type: EXPERIMENTAL

Ketamine 0.71 mg/kg

Intervention Type: DRUG

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

LZP

Lorazepam 2 mg infused over 52 minutes (LZP)

Group Type: EXPERIMENTAL

Lorazepam 2 mg

Intervention Type: DRUG

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

Interventions

Ketamine 0.41 mg/kg

52 minute iv infusion of ketamine 0.41 mg/kg

Intervention Type: DRUG

Ketamine 0.71 mg/kg

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

Intervention Type: DRUG

Lorazepam 2 mg

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

Intervention Type: DRUG

Other Intervention Names

K1; K2; LZP

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 52 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Elias Dakwar

Assistant Professor Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elias Dakwar, MD

Role: PRINCIPAL_INVESTIGATOR

NYSPI/Columbia College of Physicians and Surgeons

Carl Hart, PhD

Role: STUDY_CHAIR

NYSPI/Columbia College of Physicians and Surgeons

Locations

NYSPI

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24035344 (View on PubMed)

Other Identifiers

#6162

Identifier Type: -

Identifier Source: org_study_id