Glutamatergic Modulation of Motivation Enhancement: A Pilot Feasibility Trial

This study evaluates the feasibility of a treatment paradigm that involves naturalistic cocaine use opportunities in the context of psychotherapy aimed at utilizing these opportunities therapeutically.

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorders
• Intervention / Treatment: Drug: infusion of NMDA antagonist

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criterion Method of Ascertainment

1. Active cocaine dependence with at least 8 days of use or at least 4 binges of large amounts (>$200/occasion) over the past 30 days, and displaying at least one positive utox during screening SCID, Psychiatric Interview, self-report, utox
2. Physically healthy Laboratory tests (urinalysis, blood chemistry, 12-lead ECG in normal limits), physical examination, self-reported medical history
3. No adverse reactions to study medications Subjects will be asked about previous exposure to ketamine and midazolam
4. 21-55 years of age Self-reported age, verification with legal identification
5. Capacity to consent and comply with study procedures, including sufficient proficiency in English A short written test about study procedures, SCID, psychiatric interview
6. Seeking treatment Psychiatric Interview, self-report

Exclusion Criterion Method of Ascertainment

1. Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance induced psychosis, and current substance-induced mood disorder with HAMD score > 12. Psychiatric Interview, SCID, HAMD
2. Physiological dependence on another substance, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis SCID, Psychiatric Interview
3. Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders SCID, Psychiatric Interview
4. Current suicide risk or a history of suicide attempt within the past year SCID, Psychiatric Interview
5. Pregnant or interested in becoming pregnant during the study period Blood and urine pregnancy testing, self-report
6. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse Laboratory tests (12-lead ECG in normal limits), physical examination, self-reported medical history
7. Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), WBC < 3.5, active hepatitis or other liver disease with elevated transaminase levels (< 2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creat > 2, BUN >40), or untreated diabetes Physiological tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, self-reported medical history
8. Previous history of ketamine or midazolam misuse or abuse, and a history of an adverse reaction/experience with prior exposure to cocaine, ketamine or midazolam Physical examination, self-reported medical history
9. Recent history of significant violence (past 2 years) SCID, Psychiatric Interview
10. Abnormal pseudocholinesterase level Blood testing
11. First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS) SCID, Psychiatric Interview
12. BMI > 35, or a history of documented obstructive sleep apnea Physical examination, self-reported medical history
13. On psychotropic or other medications whose effect could be disrupted by participation in the study Psychiatric interview, self-reported medical history
14. Patients who cannot comply with study procedures during the initial hospitalization phase Study Performance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: open-label; 52 minute infusion of NMDA antagonist	Drug: infusion of NMDA antagonist; 52 minute infusion; Other Names: NMDA antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine Use	Participants were provided choices to use up to 5 hits of cocaine on up to 2 occasions (cocaine versus money). Participants who chose cocaine (1 or more hits) during the first choice opportunity are administered a 52 minute infusion of 0.71 mg/kg ketamine the following day. Another choice opportunity occurs 24 hours later. The primary outcome is the choice participants made during these occasions	5 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: elias dakwar, NYSPI

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 20, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Agents; Excitatory Amino Acid Agonists; N-Methylaspartate
• Other Study ID Numbers: 7051