Substance Withdrawal Syndrome
Conditions
Brief summary
Prescription opioid addiction is a growing public health problem and more pharmacologic treatments are needed because current approved medications have had limited patient acceptance (naltrexone), limited availability (methadone), and concerns about misuse and diversion (methadone and buprenorphine). Tramadol is a currently approved medication used to treat moderate-severe pain, and initial studies demonstrate that it may be useful for treatment of the uncomfortable syndrome of opioid withdrawal without producing euphoric effects. This study will determine whether two different doses of extended release tramadol can treat opioid withdrawal and whether tramadol itself produces withdrawal after it is no longer taken.
Interventions
DRUGTramadol
Oral Medication
DRUGPlacebo
Oral Medication
Sponsors
National Institute on Drug Abuse (NIDA)
Michelle Lofwall
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Addicted to opioids
Exclusion criteria
* Any major medical or psychiatric disorder that would be contraindicated for participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Opioid Withdrawal Total Adjective Score | Days 1-7 | range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present. T |
| Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1 | Days 1-7 | There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses. |
| Subjective Opioid Withdrawal Adjective Total Score Week 2 | days 8-13 | range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present |
| Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2 | Days 8-13 (all groups now on placebo) | There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses. |
Countries
United States
Participant flow
Recruitment details
Outpatient screening. Recruitment by advertisement and word or mouth.
Pre-assignment details
Persons screening who did not meet inclusion/ exclusion criteria were not enrolled. Persons who did not complete the study were not included in analyses. The study was designed as an efficacy study that a priori stated it would enroll until 12 persons in each group completed the study and analyse only completers. No serious AEs in noncompleters.
Participants by arm
| Arm | Count |
|---|---|
| Tramadol 200 mg Medication: Extended release tramadol for 1 week and then placebo given for 1 week | 12 |
| Placebo Medication: Placebo given for two weeks | 12 |
| Tramadol 600 mg Medication: Extended release tramadol 600 mg given for 1 week and then placebo given for 1 week | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 3 |
Baseline characteristics
| Characteristic | Placebo | Tramadol 600 mg | Tramadol 200 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 12 Participants | 36 Participants |
| Age, Continuous | 32.2 years STANDARD_DEVIATION 2.2 | 31.6 years STANDARD_DEVIATION 1.5 | 26.8 years STANDARD_DEVIATION 0.9 | 30.1 years STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 12 participants | 12 participants | 12 participants | 36 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 7 Participants | 22 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 | 2 / 17 | 1 / 19 | 2 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 19 | 0 / 17 |
Outcome results
Primary
Subjective Opioid Withdrawal Adjective Total Score Week 2
range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present
Time frame: days 8-13
Population: The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean total withdrawal score across the days listed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol 200 mg Daily | Subjective Opioid Withdrawal Adjective Total Score Week 2 | 2.7 units on a scale | Standard Error 0.2 |
| Placebo | Subjective Opioid Withdrawal Adjective Total Score Week 2 | 2.9 units on a scale | Standard Error 0.2 |
| Tramadol 600 mg Daily | Subjective Opioid Withdrawal Adjective Total Score Week 2 | 2.7 units on a scale | Standard Error 0.1 |
Primary
Subjective Opioid Withdrawal Total Adjective Score
range of scores is 0-84; low scores indicate no opioid withdrawal, higher scores indicating more opioid withdrawal present. T
Time frame: Days 1-7
Population: The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean across the days listed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol 200 mg Daily | Subjective Opioid Withdrawal Total Adjective Score | 5.8 units on a scale | Standard Error 0.1 |
| Placebo | Subjective Opioid Withdrawal Total Adjective Score | 7.7 units on a scale | Standard Error 0.1 |
| Tramadol 600 mg Daily | Subjective Opioid Withdrawal Total Adjective Score | 6.9 units on a scale | Standard Error 0.1 |
Primary
Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1
There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses.
Time frame: Days 1-7
Population: These are data from week 1 -- the 12 people who completed this week in each group. This is the analysis that was specified at the start of the study. The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean across the days listed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol 200 mg Daily | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1 | 1.8 Mean doses per day | Standard Error 0.2 |
| Placebo | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1 | 2.5 Mean doses per day | Standard Error 0.2 |
| Tramadol 600 mg Daily | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 1 | 3.1 Mean doses per day | Standard Error 0.3 |
Primary
Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2
There were four medications (acetaminophen for aches/pains, zolpidem for trouble sleeping, bismuth subsalicylate for diarrhea, and alumina/magnesia/simethicone for nausea/upset stomach) available to all volunteers in all treatment arms to help relieve any withdrawal symptoms that were not relieved by the blinded tramadol/placebo doses.
Time frame: Days 8-13 (all groups now on placebo)
Population: The primary analysis was ANOVA with day and treatment arm as factors. The outcome measure described below is the mean number of doses/day across the days listed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol 200 mg Daily | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2 | 1.8 mean # of doses per day | Standard Error 0.2 |
| Placebo | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2 | 1.6 mean # of doses per day | Standard Error 0.1 |
| Tramadol 600 mg Daily | Total Number of Breakthrough Withdrawal Medication Doses Taken Week 2 | 3.2 mean # of doses per day | Standard Error 0.2 |