Cocaine Dependence
Conditions
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: 1. ketamine and MBRP will significantly increase the time to first use compared to placebo and MBRP in cocaine-dependent individuals. 2. ketamine and MBRP is significantly more likely to lead to abstinence from cocaine (no use over one week) as compared to placebo and MBRP. 3. ketamine and MBRP will significantly reduce subjective, endocrine, and physiological responses to stress (including cue exposure) as compared to placebo and MBRP. 4. ketamine and MBRP will significantly increase mindfulness, as assessed by the Five Facet Mindfulness Questionnaire (FFMQ), as compared to placebo and MBRP.
Interventions
DRUGKetamine
0.5 mg/kg IV over 40 minutes
DRUGMidazolam
0.025 mg/kg IV over 40 minutes
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cocaine Use/Drop Out | Over the four week period following discharge from the inpatient unit at Day 5 | 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 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 | Abstinence is defined as 2 or greater weeks of no cocaine use, as ascertained by the TLFB and urine toxicology. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine 0.5 mg/kg of ketamine IV over 40 minutes
Ketamine: 0.5 mg/kg IV over 40 minutes | 27 |
| Midazolam 0.025 mg/kg IV over 40 minutes
Midazolam: 0.025 mg/kg IV over 40 minutes | 28 |
| Total | 55 |
Baseline characteristics
| Characteristic | Ketamine | Total | Midazolam |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 2 | 47 years STANDARD_DEVIATION 1 | 49 years STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 34 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 2 Participants |
| Region of Enrollment United States | 27 Participants | 55 Participants | 28 Participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 9 Participants |
| Sex: Female, Male Male | 22 Participants | 41 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 3 / 27 | 7 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 28 |
Outcome results
Primary
Abstinence
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Abstinence | 13 Participants |
| Midazolam | Abstinence | 3 Participants |
Primary
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.
Time frame: Over the four week period following discharge from the inpatient unit at Day 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Participants With Cocaine Use/Drop Out | 16 Participants |
| Midazolam | Number of Participants With Cocaine Use/Drop Out | 26 Participants |