Cocaine-Related Disorders, Anhedonia
Conditions
Brief summary
The purpose of this study is to examine anhedonia as a potential moderator of treatment outcomes for Cocaine Use Disorder (CUD). Specifically, this study will investigate how anhedonia affects outcomes in contingency management (CM) treatment for CUD and whether anhedonia mediates the effects of adjunctive treatment with a dopaminergic (DAergic) drug, d-amphetamine, on outcomes in CM for CUD, as well as investigate the contribution of anhedonia to overall CUD severity.
Detailed description
Recent research suggests that anhedonia is a key neurobehavioral dysfunction in Cocaine Use Disorder (CUD) that contributes to treatment outcomes. Anhedonia, defined here as lack of interest or pleasure in non-drug rewards, is frequently found in CUD and is related to neural deficits, such as low striatal dopamine and deficient activation to non-drug rewards in mesocortical circuits. Interestingly, not all individuals in CUD have these deficits. Preliminary data suggests that the presence of self-reported anhedonia predicts worse outcome in contingency management (CM) treatment of CUD. Moreover, low baseline dopamine predicts failure to attain abstinence in CM while medications that enhance DA increase CM success rates and responsiveness to rewards. This study specifically aims to test the contribution of anhedonia to overall CUD severity, the relationship of anhedonia to outcomes in CM treatment, and the mediating role of anhedonia in medication enhancement of CM in CUD. To accomplish these aims, individuals with CUD will be enrolled and will undergo 4 weeks of intensive CM treatment, either with or without treatment with the dopaminergic drug, d-amphetamine. A medication only group will be included to solely measure the effects of d-amphetamine. Anhedonia will be assessed using multi-modal subjective, psychophysiological and behavioral measures of reward functioning at baseline, and each week of treatment. Functional magnetic resonance imaging (fMRI) measures of reward functioning will also be taken at baseline and week 4 in a subset of participants (n = 24)
Interventions
DRUGd-amphetamine
Participants in this group will receive 60 mg of d-amphetamine daily for 4 weeks. There will be a 1 week run up dosing and a 1 week run-down medication period.
BEHAVIORALContingency management
Contingency management is an established cocaine use disorder treatment in which individuals receive monetary rewards for abstinence.
DRUGPlacebo (for d-amphetamine)
60 mg of riboflavin and cornstarch as needed.
Sponsors
The University of Texas Health Science Center, Houston
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* be between 18 and 60 years of age * meet Diagnostic and Statistical Manual V (DSM-5) criteria for current cocaine use disorder of at least moderate severity (≥ 4 symptoms) * have at least 1 cocaine positive urine sample during the baseline screening period * be in acceptable health on the basis of interview, medical history and physical exam, per the judgment of our study physician * be able to understand the consent form and provide written informed consent * be able to provide the names of at least 2 persons who can generally locate their whereabouts. * if female, agree to use an acceptable method of birth control during study (surgical sterilization, approved hormonal contraceptives, barrier methods with spermicide, or intrauterine device).
Exclusion criteria
* current DSM-5 diagnosis for substance use disorder of least moderate severity (≥ 4 symptoms), other than cocaine, nicotine, marijuana, or alcohol * Physical dependence on alcohol requiring medically supervised detoxification, in the judgment of the study physician * current amphetamine use (by self-report in past 30 days or positive urine drug screen), more than 50 lifetime uses of amphetamine, or history of DSM-5 Amphetamine Use Disorder * a current DSM-5 axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe * significant current suicidal or homicidal ideation * medical conditions contraindicating d-amphetamine (e.g., significant cardiovascular disease, liver or kidney disease, seizure disorder, hypotension or hypertension) * taking medications known to have effects on the central nervous system or that could cause significant drug interactions with d-amphetamine (e.g., clonidine, prazosin) * having conditions of probation or parole requiring reports of drug use to officers of the court * impending incarceration * pregnant or nursing for female patients * inability to read, write, or speak English Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy) | At end of active treatment (Treatment week 4) | Subjects will complete a urine drug screen each visit. Achievement of cocaine abstinence will be defined as two consecutive weeks of cocaine-negative urine samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Negative Urine Samples | At end of active treatment (Treatment week 4) | Subjects will complete a urine drug screen each visit (3x weekly). The Treatment Effectiveness Score is defined as the total number of cocaine negative urines across the 4 weeks of treatment (possible total of 12). |
Countries
United States
Participant flow
Pre-assignment details
Participants completed the baseline measures of anhedonia after consent but before assignment to group. Two participants were consented but not randomized - 1 due to high blood pressure at the baseline session, 1 lost to followup before completing the baseline session
Participants by arm
| Arm | Count |
|---|---|
| d-Amphetamine and Contingency Management Participants in this group will receive 4 weeks of treatment with 60mg of sustained release d-amphetamine with contingency management treatment for cocaine use disorder.
d-amphetamine: Participants in this group will receive 60 mg of d-amphetamine daily for 4 weeks. There will be a 1 week run up dosing and a 1 week run-down medication period.
Contingency management: Contingency management is an established cocaine use disorder treatment in which individuals receive monetary rewards for abstinence. | 21 |
| d-Amphetamine Alone Participants in this group will receive 4 weeks of treatment with 60mg of sustained release d-amphetamine but will not receive contingency management treatment for cocaine use disorder.
d-amphetamine: Participants in this group will receive 60 mg of d-amphetamine daily for 4 weeks. There will be a 1 week run up dosing and a 1 week run-down medication period. | 15 |
| Placebo and Contingency Management Participants in this group will receive 4 weeks of of placebo treatment, paired with contingency management treatment for cocaine use disorder.
Contingency management: Contingency management is an established cocaine use disorder treatment in which individuals receive monetary rewards for abstinence.
Placebo (for d-amphetamine): 60 mg of riboflavin and cornstarch as needed. | 19 |
| Total | 55 |
Baseline characteristics
| Characteristic | Total | Placebo and Contingency Management | d-Amphetamine Alone | d-Amphetamine and Contingency Management |
|---|---|---|---|---|
| Age, Continuous | 51.22 years STANDARD_DEVIATION 6.51 | 50.74 years STANDARD_DEVIATION 6.11 | 51.87 years STANDARD_DEVIATION 6.4 | 51.91 years STANDARD_DEVIATION 7.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 3 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 16 Participants | 13 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Location of Enrollment Chicago | 26 Participants | 8 Participants | 4 Participants | 14 Participants |
| Location of Enrollment Houston | 29 Participants | 11 Participants | 11 Participants | 7 Participants |
| Monthly Income in Dollars | 1673.18 USD STANDARD_DEVIATION 1650.29 | 1390.57 USD STANDARD_DEVIATION 1350 | 1858 USD STANDARD_DEVIATION 2217.13 | 1796.82 USD STANDARD_DEVIATION 1467.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants | 16 Participants | 12 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 55 participants | 19 participants | 15 participants | 21 participants |
| Sex: Female, Male Female | 9 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 46 Participants | 17 Participants | 13 Participants | 16 Participants |
| Years of Education | 13.34 years STANDARD_DEVIATION 1.91 | 12.42 years STANDARD_DEVIATION 1.54 | 13.20 years STANDARD_DEVIATION 2.21 | 14.29 years STANDARD_DEVIATION 1.59 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 15 | 0 / 19 |
| other Total, other adverse events | 11 / 21 | 11 / 15 | 17 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 15 | 1 / 19 |
Outcome results
Primary
Number of Participants Who Were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy)
Subjects will complete a urine drug screen each visit. Achievement of cocaine abstinence will be defined as two consecutive weeks of cocaine-negative urine samples.
Time frame: At end of active treatment (Treatment week 4)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| d-Amphetamine and Contingency Management | Number of Participants Who Were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy) | 3 Participants |
| d-Amphetamine Alone | Number of Participants Who Were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy) | 3 Participants |
| Placebo and Contingency Management | Number of Participants Who Were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy) | 6 Participants |
Secondary
Cocaine Negative Urine Samples
Subjects will complete a urine drug screen each visit (3x weekly). The Treatment Effectiveness Score is defined as the total number of cocaine negative urines across the 4 weeks of treatment (possible total of 12).
Time frame: At end of active treatment (Treatment week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| d-Amphetamine and Contingency Management | Cocaine Negative Urine Samples | 1.76 count of urines (range 0 - 12) | Standard Deviation 4 |
| d-Amphetamine Alone | Cocaine Negative Urine Samples | 3.33 count of urines (range 0 - 12) | Standard Deviation 4.25 |
| Placebo and Contingency Management | Cocaine Negative Urine Samples | 5.00 count of urines (range 0 - 12) | Standard Deviation 4.88 |