Adult Attention Deficit Hyperactivity Disorder, Cocaine Dependence
Conditions
Keywords
ADHD, Cocaine, Treatment
Brief summary
The proposed protocol is a 3 group double-blind, placebo-controlled outpatient study of the safety and efficacy of Adderall-XR (ER-MAS) in the treatment of comorbid ADHD and cocaine dependence. Since this medication has independently shown promise in helping with ADHD and cocaine abuse, we are proposing that it may be successful in the treatment of comorbid ADHD and cocaine abuse. We plan to enroll 75 subjects in a 14-week trial. The primary objectives of the study are to determine the efficacy of ER-MAS in promoting cocaine abstinence and improvement in ADHD symptomology among cocaine-dependent patients with comorbid ADHD.
Detailed description
Specific Aim 1: To determine the efficacy of ER-MAS in promoting cocaine abstinence and ADHD improvement among comorbid ADHD and cocaine-dependent patients. Primary Hypothesis: benzoylecgonine positive urine screens will decrease with greatest to least reductions from 80mg\>60mg\>PBO (placebo). Hypothesis 2: ADHD-Rating Scale will decrease with greatest to least reductions from 80mg\>60mg\>PBO. Specific Aim 2: To determine the effect of ER-MAS on improving general functioning and impulsivity among comorbid ADHD and cocaine-dependent patients. Hypothesis 4: There will be greater improved CGI (clinical global impression scale) scores in participants receiving d-AMPH (d-amphetamine) compared to PBO. Hypothesis 5: ER-MAS will decrease impulsivity as measured by several self-report (Barratts Impulsivity Scale) and behavioral measures (Card Sort, IMT (immediate memory task), DMT (delayed memory task), BART) compared to PBO. This 14-week, three arm (two medication doses versus PBO), prospective, parallel groups, randomized PBO-controlled trial with a lead-in as well as medication run-up and run down weeks, will provide clear data on efficacy and safety for definitive Phase III trials, which if successful will lead to improved treatment for A-ADHD/S-SUD.
Interventions
DRUGPlacebo
Placebo group
DRUGAdderall-XR
Adderall-XR 60mg/day
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
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women between the ages of 18-60 who meet DSM-IV criteria for current cocaine dependence and adult ADHD (DSM-IV-TR). 2. Used cocaine at least four days in the past month 3. Must have a Body Mass Index (BMI) \> 18 kg/m2 4. Alcohol Breathalyzer (BraC) at consent of \< 0.04% 5. Individuals must be capable of giving informed consent and capable of complying with study procedures. 6. Women of child bearing age will be included in the study provided that they are not pregnant, based on the results of a blood pregnancy test drawn at the time of screening. They must also agree to use a method of contraception with proven efficacy and agree not to become pregnant during the study. To confirm this, blood pregnancy tests will be repeated monthly. Women will be provided a full explanation of the potential dangers of pregnancy while on the study medication. If a woman becomes pregnant, the study medication will be discontinued.
Exclusion criteria
1. Meets DSM-IV-TR criteria for bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse. 2. Individuals with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment are unstable or would be disrupted by study medication or are likely to require pharmacotherapy during the study period. 3. Individuals with current major depressive disorder.However,individuals who are currently stable on a psychotropic medication for three months with a HAM-D \<14 may be included. 4. Individuals physiologically dependent on any other drugs (excluding nicotine or cannabis) which require medical intervention. 5. Individuals with current suicidal risk. 6. Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG, cardiac symptoms, fainting, open-heart surgery and/or arrhythmia, and family history of ventricular tachycardia/sudden death. 7. Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension (SBP \> 140, DBP\> 90, or HR \> 100 when sitting quietly), acute hepatitis (patients with chronic mildly elevated transaminases \< 3x upper limit of normal are acceptable), or uncontrolled diabetes. 8. Individuals with a history of seizures 9. History of allergic reaction to candidate medication (amphetamine and/or ER-MAS). 10. Women who are pregnant or nursing. 11. History of failure to respond to a previous adequate trial of the candidate medication for cocaine dependence 12. Individuals who are legally mandated (e.g., to avoid incarceration, monetary or other penalties, etc.) to participate in substance abuse treatment program 13. History of glaucoma 14. Individuals who report use of MAOI within 14 days of study start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Last Three Weeks of Cocaine Abstinence Based on Urine Toxicology Results and Self Reported Use | weekly for 14 weeks of trial or for length of participation | Each week after randomization was scored dichotomously as cocaine positive or negative. Cocaine use was positive if any urine or self-report was positive. Cocaine use was negative if all urines (BE \<300 ng/ml) and all self-report were negative. Weeks with no urine or no self-report were designated missing. |
| ADHD Symptoms Based on ADHD Rating Scale | measured once per week for 14 weeks or length of study participation | The proportion of subjects exhibiting \>30% reduction of AISRS score at last enrollment week compared to week 0 |
Countries
United States
Participant flow
Pre-assignment details
Study consisted of a one week single blind placebo run-in prior to group assignment. 139 participants were enrolled and 126 were randomized following the placebo run-up
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo
Placebo: Placebo group | 43 |
| Adderall-XR 60 mg Adderall-XR 60 mg
Adderall-XR: Adderall-XR 60mg/day | 40 |
| Adderall-XR 80 mg Adderall-XR 80 mg
Adderall-XR: Adderall-XR 80mg/day | 43 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | incarceration | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 10 | 9 | 5 |
| Overall Study | moved | 1 | 0 | 1 |
| Overall Study | non-compliance | 0 | 0 | 2 |
| Overall Study | wanted treatment elsewhere | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Adderall-XR 80 mg | Adderall-XR 60 mg |
|---|---|---|---|---|
| Age, Continuous | 39.3 YEARS STANDARD_DEVIATION 7.4 | 40.4 YEARS STANDARD_DEVIATION 8.1 | 38.4 YEARS STANDARD_DEVIATION 8.6 | 43.9 YEARS STANDARD_DEVIATION 7.5 |
| Days of cocaine use (prior 28 days) | 11.3 DAYS STANDARD_DEVIATION 7.5 | 11.7 DAYS STANDARD_DEVIATION 7.4 | 11.3 DAYS STANDARD_DEVIATION 7 | 12.4 DAYS STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 22 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 26 Participants | 8 Participants | 8 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 72 Participants | 27 Participants | 21 Participants |
| Sex: Female, Male Female | 5 Participants | 20 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Male | 38 Participants | 106 Participants | 35 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 43 | 19 / 40 | 19 / 43 |
| serious Total, serious adverse events | 2 / 43 | 0 / 40 | 0 / 43 |
Outcome results
Primary
ADHD Symptoms Based on ADHD Rating Scale
The proportion of subjects exhibiting \>30% reduction of AISRS score at last enrollment week compared to week 0
Time frame: measured once per week for 14 weeks or length of study participation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | ADHD Symptoms Based on ADHD Rating Scale | 17 participants |
| Adderall-XR 60 mg | ADHD Symptoms Based on ADHD Rating Scale | 30 participants |
| Adderall-XR 80 mg | ADHD Symptoms Based on ADHD Rating Scale | 25 participants |
Primary
Last Three Weeks of Cocaine Abstinence Based on Urine Toxicology Results and Self Reported Use
Each week after randomization was scored dichotomously as cocaine positive or negative. Cocaine use was positive if any urine or self-report was positive. Cocaine use was negative if all urines (BE \<300 ng/ml) and all self-report were negative. Weeks with no urine or no self-report were designated missing.
Time frame: weekly for 14 weeks of trial or for length of participation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Last Three Weeks of Cocaine Abstinence Based on Urine Toxicology Results and Self Reported Use | 7 percentage of participants |
| Adderall-XR 60 mg | Last Three Weeks of Cocaine Abstinence Based on Urine Toxicology Results and Self Reported Use | 18 percentage of participants |
| Adderall-XR 80 mg | Last Three Weeks of Cocaine Abstinence Based on Urine Toxicology Results and Self Reported Use | 30 percentage of participants |