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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Barth Wilsey, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00314340
First received: April 11, 2006
Last updated: July 11, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Chronic Pain
Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity
Drug: ER Morphine
Drug: hydrocodone plus acetaminophen
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A CTSC Clinical Research Center Study: A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • 3 Scores on the Addiction Research Center Inventory (ARCI) [ Time Frame: 0, 60, 120, 180, 240, or 300 minutes ] [ Designated as safety issue: No ]
    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.


Enrollment: 12
Study Start Date: November 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.
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: placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00314340

Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Barth L Wilsey, MD University of California, CA Medical Center Division of Pain Medicine
  More Information

Publications:
Responsible Party: Barth Wilsey, Research Professor, University of California, Davis
ClinicalTrials.gov Identifier: NCT00314340     History of Changes
Other Study ID Numbers: 200513430
Study First Received: April 11, 2006
Results First Received: November 20, 2012
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
Chronic Pain
Opioids

Additional relevant MeSH terms:
Chronic Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Morphine
Hydrocodone
Acetaminophen
Amphetamine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Antipyretics
Antitussive Agents
Respiratory System Agents
Central Nervous System Stimulants
Sympathomimetics
Autonomic Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents

ClinicalTrials.gov processed this record on September 22, 2014