Chronic Pain
Conditions
Keywords
Chronic Pain, Opioids
Brief summary
Characterize the relative abuse liability of a short versus a long acting opioid in chronic pain patients.
Detailed description
A placebo-controlled, double-blind, crossover trial will be conducted providing study subjects either hydrocodone/acetaminophen 30mg/975mg, sustained release morphine 45mg or placebo on separate GCRC visits. A long acting comparator (slow-release morphine sulfate 45 mg) will be chosen because of its putative equianalgesic effects to the dose of hydrocodone (30 mg) selected. Subjects will participate in the three sessions at the UC Davis/Mather Medical Center General Clinical Research Center (GCRC) at intervals of 7-10 days. Sessions will be approximately 360 min in duration. Subjects will receive either hydrocodone/acetaminophen or sustained release morphine around-the-clock for 7-10 days prior to the experimental session. At each experimental session, an assessment of abuse liability will be completed before the intake of medications, as well as at 0, 60, 120, 180, 240 minutes after the ingestion of the study medication.
Interventions
BEHAVIORALMarkers of Abuse Liability, Neuropsych Testing, and Cue Reactivity
The first dose of the study medication was taken following collection of baseline measurements, and subsequent measurements were taken hourly thereafter. Respiration, heart rate, arterial oxygen saturation (pulse oximetry), and blood pressure were also monitored at these intervals to insure the safety of subjects.
DRUGER Morphine
DRUGhydrocodone plus acetaminophen
DRUGplacebo
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients with chronic pain for periods greater than 6 months * Patients taking greater than 80 mg morphine equivalents of a short acting opioid (\>8 vicodin or 4 oxycodone/day) * Referral to Pain or Substance Abuse Clinic for self-escalation of opioids
Exclusion criteria
* Inability to understand and comprehend spoken English * Patients with Munchausen's syndrome * Patient has a history of Peripheral Vascular Disease * Patient has a history of Raynaud's Phenomenon * Liver Disease; Child's classification greater than 1 (liver cirrhosis) will be excluded * Renal disease (BUN \>25 or Cr \>1.5) * Congestive Heart Failure; Subjects with New York Heart Association (NYHA)Heart Failure Symptom Classification System Level of Impairment II, III and IV will be excluded * Coronary artery disease; recent MI within the past six months or recent history of angina not controlled with NTG within the past six months * Hypertension; 1)previously normotensive subject; systolic bp \>140 mm Hg and diastolic bp \> 90 mm Hg 2) Hx of active treatment with antihypertensive medications; systolic bp \>150 mm Hg and diastolic bp \> 100 mm Hg * Cerebrovascular disease; recent history within the past year of a transient ischemic attack or recent history within the past year of a cerebrovascular event * Malignancy requiring active treatment * Patient is pregnant (as ascertained by a self-report and a mandatory commercial pregnancy test before any study medication is consumed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3 Scores on the Addiction Research Center Inventory (ARCI) | 0, 60, 120, 180, 240, or 300 minutes | The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria. |
Participant flow
Recruitment details
Participants were recruited from the UC Davis Medical Center Pain and VA Northern California Pain Clinics in 2007-8. They had to have had chronic pain for more than 3 months and to have self-escalated their dose of a short-acting opioid (i.e., a combination product containing hydrocodone, codeine, or oxycodone)prescribed to treat their pain.
Pre-assignment details
Of 55 patients approached, 18 were evaluated, and 14 met entry criteria and were enrolled. Two withdrew before starting the study. One subject withdrew after starting the study because of insufficient pain relief from the study medications leaving 35 visits by 12 patients for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Prescription Opioid Abusers The subjective effects of the study drug were evaluated with the short form of the Addiction Research Center Inventory (ARCI. This inventory consists of 49 true/ false questions which survey major domains of drug effects. Participants indicated the pleasurable effects or desirability of the medications on 4 locally developed drug-liking ratings: craving, liking, strong desire, and want more pain medication. Ratings were made on a 100-mm VAS anchored with 0 at the low end and 10 at the high end. Participants also responded to 11 locally developed drug-effect ratings to assess psychoactive effects. Ratings were again made on a 100-mmVAS anchoredwith 0 at the lowend and 10 at the high end for:on cloud 9, high, good drug effect, bad drug effect, impaired,stoned, sedated, confused, nauseated from, anxious, and down. The rating levels over a six hour period were examined to explore the timing of these effects. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | lost interest | 1 |
Baseline characteristics
| Characteristic | Prescription Opioid Abusers |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
3 Scores on the Addiction Research Center Inventory (ARCI)
The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria.
Time frame: 0, 60, 120, 180, 240, or 300 minutes
Population: Treatment effects at baseline, 60, 120, 180, 240, and 300 min were assessed with repeated measures ANOVA. A liner mixed-effects model with inclusion of interaction terms (1) treatment and time and (2) random order visit number and time was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ER Morphine Tablets, 45mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | peak euphoria | 3.3 scores on a scale | Standard Deviation 0.8 |
| ER Morphine Tablets, 45mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough sedation | 7.6 scores on a scale | Standard Deviation 1 |
| ER Morphine Tablets, 45mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough agitation | 4.7 scores on a scale | Standard Deviation 0.8 |
| Hydrocodone 30 mg Plus N-acetyl-para-aminophenol 975 mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | peak euphoria | 4.6 scores on a scale | Standard Deviation 0.9 |
| Hydrocodone 30 mg Plus N-acetyl-para-aminophenol 975 mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough sedation | 5.4 scores on a scale | Standard Deviation 0.9 |
| Hydrocodone 30 mg Plus N-acetyl-para-aminophenol 975 mg | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough agitation | 4.2 scores on a scale | Standard Deviation 0.6 |
| Placebo | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough sedation | 5.2 scores on a scale | Standard Deviation 0.8 |
| Placebo | 3 Scores on the Addiction Research Center Inventory (ARCI) | trough agitation | 3.6 scores on a scale | Standard Deviation 0.5 |
| Placebo | 3 Scores on the Addiction Research Center Inventory (ARCI) | peak euphoria | 3.5 scores on a scale | Standard Deviation 1 |