A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine

Study Overview
=================
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.

Official Title
-----------------
A CTSC Clinical Research Center Study: A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine

Conditions
-----------------
Chronic Pain

Intervention / Treatment
-----------------
* Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity
* Drug: ER Morphine
* Drug: hydrocodone plus acetaminophen
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: extended-release morphine<br>Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity On one of three study dates, subjects received ER morphine tablets, 45 mg (Mallinckrodt Pharmaceuticals, St. Louis, MO). The dose of ER morphine sulfate (45 mg) was selected because of its approximate equianalgesic effect to the dose of hydrocodone-acetaminophen (30/925 mg). | Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity<br>* 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.<br>* Other names: Neurocognitive testing;Drug: ER Morphine<br> <br> * Other names: extended release morphine;|
| Active Comparator: hydrocodone<br>Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity On the day of the study session, patients received hydrocodone 30 mg plus N-acetyl-para-aminophenol 975 mg (APAP;Qualitest Pharmaceuticals Inc, Huntsville, AL). | Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity<br>* 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.<br>* Other names: Neurocognitive testing;Drug: hydrocodone plus acetaminophen<br> <br> |
| Placebo Comparator: placebo<br>Subjects received a placebo pill if randomized to this arm. Both opioid medications and the placebo were administered in identical capsules. | Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity<br>* 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.<br>* Other names: Neurocognitive testing;Drug: placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0, 60, 120, 180, 240, or 300 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Pain, Opioids