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

May 25, 2017 updated by: University of California, Davis

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

Characterize the relative abuse liability of a short versus a long acting opioid in chronic pain patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
Behavioral: 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.
Other 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
Drug: ER Morphine
Other Names:
  • extended release morphine
Active Comparator: 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).
Behavioral: 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.
Other 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
Drug: hydrocodone plus acetaminophen
Placebo Comparator: placebo
Subjects received a placebo pill if randomized to this arm. Both opioid medications and the placebo were administered in identical capsules.
Drug: placebo
Behavioral: 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.
Other 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 Scores on the Addiction Research Center Inventory (ARCI)
Time Frame: 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.
0, 60, 120, 180, 240, or 300 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Investigators

  • Principal Investigator: Barth L Wilsey, MD, University of California, CA Medical Center Division of Pain Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

April 1, 2008

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

April 11, 2006

First Submitted That Met QC Criteria

April 11, 2006

First Posted (Estimate)

April 13, 2006

Study Record Updates

Last Update Posted (Actual)

May 30, 2017

Last Update Submitted That Met QC Criteria

May 25, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200513430

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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