The Effect of Glutamatergic Modulation on Cocaine Self-administration

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02596022
• Collaborator: (none)
• Enrollment: 18
• Arms: 2
• Duration (Months): 25

Study Details

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
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jul 1, 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) [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

Criteria

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

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

Locations

No locations specified.

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elias Dakwar, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02596022
• Other Study ID Numbers: 6716
• First Posted: Nov 4, 2015
• Last Update Posted: Jun 15, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Cocaine-Related Disorders; Ketamine

Study Results

Participant Flow

Arm/Group Title	CI-581a First, Followed by CI-581b	CI-581b First, Followed by CI-581a
Arm/Group Description	Administration of CI-581a followed 2 weeks later by CI-581b CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session	Administration of CI-581b followed 2 weeks later by CI-581a CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session
Period Title: Overall Study
STARTED	10	8
COMPLETED	10	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	CI-581a First, Followed by CI-581b	CI-581b First, Followed by CI-581a	Total
Arm/Group Description	Administration of CI-581a followed 2 weeks later by CI-581b CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session	Administration of CI-581b followed 2 weeks later by CI-581a CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session	Total of all reporting groups
Overall Participants	10	8	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.6 (6.1)	48.6 (6.1)	48.6 (6.1)
Sex: Female, Male (Count of Participants)
Female	4 40%	5 62.5%	9 50%
Male	6 60%	3 37.5%	9 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 80%	6 75%	14 77.8%
White	2 20%	2 25%	4 22.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	8 100%	18 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CI-581a	CI-581b
Arm/Group Description	CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session	CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session
Measure Participants	18	18
Mean (Standard Deviation) [number of cocaine choices]	1.61 (1.3)	4.33 (1.8)

Adverse Events

Time Frame	6 weeks.
Arm/Group Title	CI-581a First, Followed by CI-581b		CI-581b First, Followed by CI-581a
Arm/Group Description	Administration of CI-581a followed 2 weeks later by CI-581b CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session		Administration of CI-581b followed 2 weeks later by CI-581a CI-581a: a 50 minute infusion 24 hours prior to cocaine self-administration session CI-581b: a 50 minute infusion 24 hours prior to cocaine self-administration session
All Cause Mortality
	CI-581a First, Followed by CI-581b		CI-581b First, Followed by CI-581a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Serious Adverse Events
	CI-581a First, Followed by CI-581b		CI-581b First, Followed by CI-581a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	CI-581a First, Followed by CI-581b		CI-581b First, Followed by CI-581a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.