The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence
Primary Purpose
Cocaine Dependence
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Midazolam
Sponsored by
About this trial
This is an interventional treatment trial for Cocaine Dependence
Eligibility Criteria
Inclusion Criteria:
- 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
- Physically healthy
- No adverse reactions to study medications
- 21-60 years of age
- Capacity to consent and comply with study procedures, including sufficient proficiency in English
- Seeking treatment
Exclusion Criteria:
- 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.
- Physiological dependence on another substance requiring medical management, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis
- Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders
- Current suicide risk or a history of suicide attempt within the past year
- Pregnant or interested in becoming pregnant during the study period
- 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), 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 (creatinine > 2, BUN >40), or untreated diabetes
- Previous history of ketamine or benzodiazepine misuse or abuse, and a history of an adverse reaction/experience with prior exposure to ketamine or benzodiazepine
- Recent history of significant violence (past 2 years)
- First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
- BMI > 32, or a history of documented obstructive sleep apnea
- On psychotropic or other medications whose effect could be disrupted by participation in the study
- Patients who cannot comply with study procedures during the initial hospitalization phase
Sites / Locations
- New York State Psychiatric Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ketamine
midazolam
Arm Description
0.5 mg/kg of ketamine IV over 40 minutes
0.025 mg/kg IV over 40 minutes
Outcomes
Primary Outcome Measures
Number of Participants With Cocaine Use/Drop Out
Number of participants who use cocaine and drop from study. During phase 2, patients will be assessed twice weekly by TLFB and urine toxicology for cocaine use. The day of first use will determine the length of time that transpired from discharge to the first lapse onto cocaine.
Abstinence
Abstinence is defined as 2 or greater weeks of no cocaine use, as ascertained by the TLFB and urine toxicology.
Secondary Outcome Measures
Full Information
NCT ID
NCT01535937
First Posted
December 29, 2011
Last Updated
April 16, 2019
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT01535937
Brief Title
The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
An analysis demonstrated that running the final participants was unnecessary.
Study Start Date
February 2012 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
April 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This project will evaluate the effect of a single sub-anesthetic dose of ketamine on the time to first cocaine use and abstinence rates in 60 treatment-seeking cocaine-dependent individuals receiving mindfulness-based relapse prevention (MBRP) therapy, using a 5 week combined laboratory-inpatient and outpatient double-blind, randomized, controlled trial.
Detailed Description
he study will begin with an inpatient phase (phase 1) of 5 days, during which abstinence is achieved, followed by a 4 week outpatient phase (phase 2). A single infusion of ketamine or midazolam will occur on day 3 of Phase 1. In addition to measures of mindfulness and impulsivity, stress sensitivity tests are incorporated into the design in order to elucidate mechanisms of action. The study hypotheses are:
ketamine and MBRP will significantly increase the time to first use compared to placebo and MBRP in cocaine-dependent individuals.
ketamine and MBRP is significantly more likely to lead to abstinence from cocaine (no use over one week) as compared to placebo and MBRP.
ketamine and MBRP will significantly reduce subjective, endocrine, and physiological responses to stress (including cue exposure) as compared to placebo and MBRP.
ketamine and MBRP will significantly increase mindfulness, as assessed by the Five Facet Mindfulness Questionnaire (FFMQ), as compared to placebo and MBRP.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Dependence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ketamine
Arm Type
Experimental
Arm Description
0.5 mg/kg of ketamine IV over 40 minutes
Arm Title
midazolam
Arm Type
Active Comparator
Arm Description
0.025 mg/kg IV over 40 minutes
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
ketamine 0.5 mg/kg
Intervention Description
0.5 mg/kg IV over 40 minutes
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
midazolam 0.025 mg/kg
Intervention Description
0.025 mg/kg IV over 40 minutes
Primary Outcome Measure Information:
Title
Number of Participants With Cocaine Use/Drop Out
Description
Number of participants who use cocaine and drop from study. During phase 2, patients will be assessed twice weekly by TLFB and urine toxicology for cocaine use. The day of first use will determine the length of time that transpired from discharge to the first lapse onto cocaine.
Time Frame
Over the four week period following discharge from the inpatient unit at Day 5
Title
Abstinence
Description
Abstinence is defined as 2 or greater weeks of no cocaine use, as ascertained by the TLFB and urine toxicology.
Time Frame
Abstinence will be assessed over 4 weeks starting at the last day of week 1 and continuing through the end of study at the last day of week 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Physically healthy
No adverse reactions to study medications
21-60 years of age
Capacity to consent and comply with study procedures, including sufficient proficiency in English
Seeking treatment
Exclusion Criteria:
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.
Physiological dependence on another substance requiring medical management, such as alcohol, opioids, or benzodiazepines, excluding caffeine, nicotine, and cannabis
Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders
Current suicide risk or a history of suicide attempt within the past year
Pregnant or interested in becoming pregnant during the study period
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), 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 (creatinine > 2, BUN >40), or untreated diabetes
Previous history of ketamine or benzodiazepine misuse or abuse, and a history of an adverse reaction/experience with prior exposure to ketamine or benzodiazepine
Recent history of significant violence (past 2 years)
First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
BMI > 32, or a history of documented obstructive sleep apnea
On psychotropic or other medications whose effect could be disrupted by participation in the study
Patients who cannot comply with study procedures during the initial hospitalization phase
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert Kleber, M.D.
Organizational Affiliation
NYSPI
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Elias Dakwar, MD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31230464
Citation
Dakwar E, Nunes EV, Hart CL, Foltin RW, Mathew SJ, Carpenter KM, Choi CJJ, Basaraba CN, Pavlicova M, Levin FR. A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. Am J Psychiatry. 2019 Nov 1;176(11):923-930. doi: 10.1176/appi.ajp.2019.18101123. Epub 2019 Jun 24.
Results Reference
derived
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The Effect of Brief Potent Glutamatergic Modulation on Cocaine Dependence
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