Trial Outcomes & Findings for Disulfiram for Cocaine Abuse (NCT NCT00395850)
NCT ID: NCT00395850
Last Updated: 2013-11-13
Results Overview
Urine toxicology results (dichotomous: positive or negative) for the presence of cocaine/cocaine metabolite during the disulfiram phase of the study. The change in the probability of a cocaine positive urine sample per day was assessed for each dose compared with placebo and slopes for each dose condition were calculated from Repeated Measures Genearlized Linear Models on a Binomial distribution (thus a Repeated Measures Logistic Regression)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
118 participants
Primary outcome timeframe
thrice weekly for 12 weeks
Results posted on
2013-11-13
Participant Flow
Recruitment occurred between April 2006 and September 2011. Opioid- or nonopioid dependent treatment seekers recruited via newspaper ads, radio ads, flyer, word-of-mouth and referrals and attended the Treatment Research Unit, initially located in an off-campus facility and then relocated to the the Psychiatric Research Institute (12/08).
Participants underwent either a two-week induction onto methadone (if opioid dependent) or a two-week baseline period prior to randomization to the treatment arms and receiving medication starting in week 3. Those receiving at \>1 dose of medication and completing assessments at at least 2 time points during week 3 were include in the analyses.
Participant milestones
| Measure |
Placebo
microcrystalline cellulose
|
Disulfiram 250
disulfiram at 250 mg/day
|
Disulfiram 375
Disulfiram at 375 mg/day
|
Disulfiram 500
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Pre-randomization Baseline/Induction
STARTED
|
118
|
0
|
0
|
0
|
|
Pre-randomization Baseline/Induction
COMPLETED
|
107
|
0
|
0
|
0
|
|
Pre-randomization Baseline/Induction
NOT COMPLETED
|
11
|
0
|
0
|
0
|
|
Randomization to Disulfiram/ Pre-admin
STARTED
|
27
|
25
|
30
|
25
|
|
Randomization to Disulfiram/ Pre-admin
COMPLETED
|
22
|
23
|
24
|
21
|
|
Randomization to Disulfiram/ Pre-admin
NOT COMPLETED
|
5
|
2
|
6
|
4
|
|
Disulfiram/Placebo Treatment
STARTED
|
20
|
23
|
24
|
21
|
|
Disulfiram/Placebo Treatment
COMPLETED
|
11
|
9
|
5
|
8
|
|
Disulfiram/Placebo Treatment
NOT COMPLETED
|
9
|
14
|
19
|
13
|
Reasons for withdrawal
| Measure |
Placebo
microcrystalline cellulose
|
Disulfiram 250
disulfiram at 250 mg/day
|
Disulfiram 375
Disulfiram at 375 mg/day
|
Disulfiram 500
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Pre-randomization Baseline/Induction
noncompliance (missed med/urine)
|
6
|
0
|
0
|
0
|
|
Pre-randomization Baseline/Induction
Withdrawal by Subject
|
4
|
0
|
0
|
0
|
|
Pre-randomization Baseline/Induction
Inconsistent attendance
|
1
|
0
|
0
|
0
|
|
Randomization to Disulfiram/ Pre-admin
noncompliance - missed med/urines
|
2
|
2
|
6
|
4
|
|
Randomization to Disulfiram/ Pre-admin
noncompliance with alcohol use
|
1
|
0
|
0
|
0
|
|
Randomization to Disulfiram/ Pre-admin
suicidal ideation
|
1
|
0
|
0
|
0
|
|
Randomization to Disulfiram/ Pre-admin
work schedule conflict
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Disulfiram for Cocaine Abuse
Baseline characteristics by cohort
| Measure |
Placebo
n=27 Participants
microcrystalline cellulose
|
Disulfiram 250
n=25 Participants
disulfiram at 250 mg/day
|
Disulfiram 375
n=30 Participants
Disulfiram at 375 mg/day
|
Disulfiram 500
n=25 Participants
Disulfiram at 500 mg/day
|
Total
n=107 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
27 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
107 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age Continuous
|
43.0 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
39.8 years
STANDARD_DEVIATION 11.3 • n=7 Participants
|
39.4 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
40.4 years
STANDARD_DEVIATION 10.1 • n=4 Participants
|
40.6 years
STANDARD_DEVIATION 11.0 • n=21 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
41 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
25 participants
n=7 Participants
|
30 participants
n=5 Participants
|
25 participants
n=4 Participants
|
107 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: thrice weekly for 12 weeksPopulation: number is based on those who participated long enough to have assessments completed at two time points during the disulfiram phase
Urine toxicology results (dichotomous: positive or negative) for the presence of cocaine/cocaine metabolite during the disulfiram phase of the study. The change in the probability of a cocaine positive urine sample per day was assessed for each dose compared with placebo and slopes for each dose condition were calculated from Repeated Measures Genearlized Linear Models on a Binomial distribution (thus a Repeated Measures Logistic Regression)
Outcome measures
| Measure |
Placebo
n=27 Participants
microcrystalline cellulose
|
Disulfiram 250
n=25 Participants
disulfiram at 250 mg/day
|
Disulfiram 375
n=30 Participants
Disulfiram at 375 mg/day
|
Disulfiram 500
n=25 Participants
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Cocaine Use Over Time
|
0.01 slope (change in prob of coc-pos utox/d)
|
0.007 slope (change in prob of coc-pos utox/d)
|
-0.01 slope (change in prob of coc-pos utox/d)
|
0.007 slope (change in prob of coc-pos utox/d)
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: those who were entered the disulfiram phase,e tc.
Outcome measures
| Measure |
Placebo
n=27 Participants
microcrystalline cellulose
|
Disulfiram 250
n=25 Participants
disulfiram at 250 mg/day
|
Disulfiram 375
n=30 Participants
Disulfiram at 375 mg/day
|
Disulfiram 500
n=25 Participants
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Retention
|
8.3 Weeks
Standard Deviation 5.4
|
9.0 Weeks
Standard Deviation 4.9
|
6.4 Weeks
Standard Deviation 4.7
|
8.3 Weeks
Standard Deviation 4.8
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Disulfiram 250
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Disulfiram 375
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Disulfiram 500
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=20 participants at risk
microcrystalline cellulose
|
Disulfiram 250
n=23 participants at risk
disulfiram at 250 mg/day
|
Disulfiram 375
n=24 participants at risk
Disulfiram at 375 mg/day
|
Disulfiram 500
n=21 participants at risk
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Psychiatric disorders
Suicidal ideation
|
5.0%
1/20 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/23 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/21 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Cardiac disorders
Acute COPD exacerbation
|
0.00%
0/20 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.3%
1/23 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/21 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Nervous system disorders
Spinal Abcess
|
0.00%
0/20 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/23 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.2%
1/24 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/21 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
Other adverse events
| Measure |
Placebo
n=20 participants at risk
microcrystalline cellulose
|
Disulfiram 250
n=23 participants at risk
disulfiram at 250 mg/day
|
Disulfiram 375
n=24 participants at risk
Disulfiram at 375 mg/day
|
Disulfiram 500
n=21 participants at risk
Disulfiram at 500 mg/day
|
|---|---|---|---|---|
|
Gastrointestinal disorders
GI Distress (e.g., nausea, vomiting, etc.)
|
10.0%
2/20 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
30.4%
7/23 • Number of events 9 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
25.0%
6/24 • Number of events 8 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
28.6%
6/21 • Number of events 6 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Musculoskeletal and connective tissue disorders
Slurred speech
|
0.00%
0/20 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/23 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
9.5%
2/21 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Psychiatric disorders
Confusion
|
5.0%
1/20 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/23 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
9.5%
2/21 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
General disorders
Sweating
|
10.0%
2/20 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
13.0%
3/23 • Number of events 3 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.8%
1/21 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Cardiac disorders
Increased Vital Signs (e.g., BP, HR)
|
5.0%
1/20 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
17.4%
4/23 • Number of events 5 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.3%
2/24 • Number of events 3 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
9.5%
2/21 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
General disorders
Metallic or Garlic Taste
|
10.0%
2/20 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.7%
2/23 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.3%
2/24 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
14.3%
3/21 • Number of events 3 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Gastrointestinal disorders
Dry mouth/Excessive Thirst
|
5.0%
1/20 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.7%
2/23 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/21 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
13.0%
3/23 • Number of events 3 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.2%
1/24 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.8%
1/21 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
General disorders
Lethargy/Sedation
|
5.0%
1/20 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.3%
1/23 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.3%
2/24 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
14.3%
3/21 • Number of events 3 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/20 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.3%
1/23 • Number of events 1 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
4.8%
1/21 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
|
Psychiatric disorders
Anxiety/Nervousness
|
0.00%
0/20 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
8.7%
2/23 • Number of events 2 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/24 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
0.00%
0/21 • 12 weeks (during disulfiram phase) plus 2 wk washout
although participants were out of the protocol at the end of week 14, because disulfiram could interact with alcohol for up to 2 weeks after stopping use, we continued to monitor participants during this time.
|
Additional Information
Dr. Alison Oliveto
University of Arkansas for Medical Sciences
Phone: 501-526-8441
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place