The Effect of Glutamatergic Modulation on Cocaine Self-administration

• ClinicalTrials.gov Identifier: NCT02596022
• Recruitment Status: Completed
• First Posted: November 4, 2015
• Results First Posted: October 17, 2017
• Last Update Posted: June 15, 2018
• Sponsor: New York State Psychiatric Institute
• Information provided by (Responsible Party): Elias Dakwar, New York State Psychiatric Institute

Study Description

Brief Summary:

Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests that glutamate modulation may work to correct these adaptations and rapidly restore motivation for delayed non-drug rewards relative to immediate drug use. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, the investigators will test the effect of CI-581a on cocaine self-administration as compared to the active control.

Condition or disease	Intervention/treatment	Phase
Cocaine Dependence	Drug: CI-581a; Drug: CI-581b	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: June 2013
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: CI-581a; Administration of CI-581a followed 2 weeks later by CI-581b	Drug: CI-581a; a 50 minute infusion 24 hours prior to cocaine self-administration session; Drug: CI-581b; a 50 minute infusion 24 hours prior to cocaine self-administration session
Active Comparator: CI-581b; Administration of CI-581b followed 2 weeks later by CI-581a	Drug: CI-581a; a 50 minute infusion 24 hours prior to cocaine self-administration session; Drug: CI-581b; a 50 minute infusion 24 hours prior to cocaine self-administration session

Outcome Measures

Primary Outcome Measures :

1. Number of Choices to Self-administer Cocaine (Out of 5 Choices) [ Time Frame: 24 hours post-infusion ]
   Participants provided 5 choices (cocaine 25 mg now vs. $11 later), with choices spaces 15 minutes apart over the course of the session.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

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
2. Physically healthy
3. No adverse reactions to study medications
4. 21-55 years of age
5. Capacity to consent and comply with study procedures, including sufficient proficiency in English
6. Not seeking treatment

Exclusion Criteria:

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.
2. Physiological dependence on another substance, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis
3. Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders
4. Current suicide risk or a history of suicide attempt within the past year
5. Pregnant or interested in becoming pregnant during the study period
6. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse
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
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
9. Recent history of significant violence (past 2 years)
10. Abnormal pseudocholinesterase level
11. First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
12. BMI > 35, or a history of documented obstructive sleep apnea
13. On psychotropic or other medications whose effect could be disrupted by participation in the study

Contacts and Locations

Sponsors and Collaborators

New York State Psychiatric Institute

Investigators

• Principal Investigator: Elias Dakwar, MD; Columbia College of Physicians and Surgeons

More Information

• Responsible Party: Elias Dakwar, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02596022
• Other Study ID Numbers: 6716
• First Posted: November 4, 2015
• Results First Posted: October 17, 2017
• Last Update Posted: June 15, 2018
• Last Verified: June 2018

Additional relevant MeSH terms:

Cocaine-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action