Evolution of Analgesic Tolerance With Opioids

April 12, 2011 updated by: University of California, San Francisco

Evolution of Analgesic Tolerance During Long Term Treatment of Chronic Pain With Opioids

The purpose of this study is to determine the extent to which analgesic tolerance develops in chronic pain patients who are either started on opioids or who receive an increase in pre-study opioid dose level and then observed during long-term (20 weeks) stable opioid therapy. In addition to clinical measures of relief of ongoing chronic pain, estimation of tolerance development will be supplemented by periodic assessment of the anti-nociceptive effects of opioids using the brief thermal sensitization model.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to determine the extent to which analgesic tolerance develops in chronic pain patients who are either started on opioids or who receive an increase in pre-study opioid dose level and then observed during long-term (20 weeks) stable opioid therapy. In addition to clinical measures of relief of ongoing chronic pain, estimation of tolerance development will be supplemented by periodic assessment of the anti-nociceptive effects of opioids using the brief thermal sensitization model.

Study Type

Interventional

Enrollment

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Pain Clinical Research Center

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

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adults who are 21-80 years of age.
  2. Desires opioid dose increase (with approval of current prescribing physician), or is not on opioids and desires a trial of opioids for ongoing pain.
  3. Expected to remain in stable health for at least a six months period surrounding study participation.
  4. Able and willing to provide written informed consent.
  5. Able to understand and follow the instructions of the investigator, including all rating scales.
  6. Stable chronic pain that is either neuropathic or non-neuropathic in origin as defined above. The diagnosis will be based on history, physical examination, and review of medical records confirming the diagnosis.
  7. For a chronic user: stable opioid use of between 31 and 150 mg/day morphine equivalent. Stable use is defined as no change in the daily dose of opioids for the month preceding study entry.
  8. For naïve users: have not used opioids or use is less than or equal to 30 mg/day morphine equivalent for their chronic pain.
  9. Chronic pain must be at least moderately severe, defined as an average daily pain severity exceeding 40 mm on a 100 mm pain intensity visual analog scale (VAS).
  10. Female subjects must be post-menopausal, physically incapable of becoming pregnant, or using acceptable birth control method. Acceptable methods of birth control include hormonal contraceptives or double-barrier methods (condom or diaphragm with spermicidal agent or IUD). If practicing an acceptable method of birth control, confirmation of negative pregnancy urine test for female subjects is required at the Screening Visit. No special precautions are required for male subjects because levorphanol is an approved therapy for chronic pain.

Exclusion Criteria:

  1. Use of opioid mixed agonist-antagonists (pentazocine, buprenorphine, butorphanol), or tramadol, will not be allowed. Use of an intrathecal opioid infusion pump will not be allowed.
  2. Allergy to levorphanol.
  3. Patients who are unable to read or speak English.
  4. A pain complaint, which is believed to be psychogenic in nature or cannot be confirmed by medical records and physical examination.
  5. Pain due to a disease, such as cancer not in remission, which is expected to substantially progress during the study period.
  6. Cognitive impairment, psychiatric disorder, or unrelated neurological disorder severe enough to interfere with assessment of pain and sensory systems.
  7. Pregnancy.
  8. Has received an investigational drug within 30 days prior to Study Visit 2.
  9. A current substance abuse disorder, a positive urine drug screen, or a history of opioid drug abuse at any time in the past.
  10. Intolerable side effects, or failed to achieve adequate analgesic effect during prior attempts at opioid dose escalation within the range of doses to be used in this study.
  11. Co-existing medical conditions or required medication use that contraindicate study procedures or opioid dose escalation. Subjects with disorders, such as unusual skin fragility or severe peripheral neuropathy that contraindicate brief thermal sensitization will be allowed to participate without this component.
  12. Those, in the opinion of the investigator, who are unlikely to comply with the study protocol or who are unsuitable for any other reason.

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

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Michael Rowbotham, MD, University of California, San Francisco

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

March 1, 2001

Primary Completion (Actual)

October 1, 2004

Study Completion (Actual)

December 1, 2005

Study Registration Dates

First Submitted

January 9, 2006

First Submitted That Met QC Criteria

January 9, 2006

First Posted (Estimate)

January 11, 2006

Study Record Updates

Last Update Posted (Estimate)

April 14, 2011

Last Update Submitted That Met QC Criteria

April 12, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H5612-23841

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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