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

NCT ID: NCT00314340

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2008-04-30

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.

Conditions

Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

extended-release morphine

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).

Group Type: ACTIVE_COMPARATOR

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Intervention Type: BEHAVIORAL

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.

ER Morphine

Intervention Type: DRUG

hydrocodone

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).

Group Type: ACTIVE_COMPARATOR

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Intervention Type: BEHAVIORAL

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.

hydrocodone plus acetaminophen

Intervention Type: DRUG

placebo

Subjects received a placebo pill if randomized to this arm. Both opioid medications and the placebo were administered in identical capsules.

Group Type: PLACEBO_COMPARATOR

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Intervention Type: BEHAVIORAL

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.

placebo

Intervention Type: DRUG

Interventions

Markers 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.

Intervention Type: BEHAVIORAL

ER Morphine

Intervention Type: DRUG

hydrocodone plus acetaminophen

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Craving for drugs on 5 visual analog scales; Addiction Research Center; Morphine-Benzedrine Group (euphoria); Phenobarbital-Chorpromazine-Alcohol (sedation); Lysergic Acid Diethylmide (dysphoria, agitation); Benzedrine (an empiric amphetamine scale); Amphetamine (activation); Cue reactivity testing; Neurocognitive testing; extended release morphine

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barth L Wilsey, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, CA Medical Center Division of Pain Medicine

References

Wilsey BL, Fishman S, Li CS, Storment J, Albanese A. Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial. Pharmacol Biochem Behav. 2009 Nov;94(1):98-107. doi: 10.1016/j.pbb.2009.07.014. Epub 2009 Aug 4.

Reference Type: RESULT

PMID: 19660492 (View on PubMed)

Other Identifiers

200513430

Identifier Type: -

Identifier Source: org_study_id