The Effects of Opioid Taper on Opioid-Induced Hyperalgesia

March 19, 2018 updated by: Georgetown University
Evidence to support the effectiveness of ongoing opioid therapy for the treatment of chronic non-malignant pain is lacking. In fact, data suggest that patient outcomes improve when tapered off opioid analgesics. To better understand the role opioid therapy plays in the experience of pain, we will study measured pain sensitivity in opioid dependent patients over the course of and 3 months following a standardized opioid taper. By isolating the effect of opioid taper in patients without pain, preliminary evidence of effect size can be used to guide clinicians treating patients with chronic pain.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Chronic pain impacts the daily lives of fully one-third of Americans over the age of 45, with prevalence expected to increase as the population ages. In well-intended and industry-driven efforts to provide relief to chronic pain sufferers, the prescription of opioids has increased dramatically since the turn of the century, such that it is currently estimated that between 5 and 8 million Americans use opioids on a daily basis for chronic pain management. Yet, prescription opioid therapy for chronic pain is not an evidence-based intervention. In fact, as evaluation data accumulate, it is becoming clear that outcomes are often poorer for patients on opioid therapy, and that improvements are appreciated when tapered off the medications. In the midst of an "epidemic of prescription drug abuse" it is critical that opioid prescription practices be evidence-based and delivered "in the best possible manner that maximizes effectiveness and minimizes harm".

A theorized explanation for poorer outcomes (functionality, quality of life) for patients on opioid therapy is the phenomenon of opioid-induced hyperalgesia (OIH). Well-demonstrated in animal and inferred in patients, ongoing opioid use results in increased sensitivity to experimental pain, which, in the case of the chronic pain patient, is believed to interfere with (if not preclude) desired pain relief outcomes. However, the causal relationship between opioid discontinuation and OIH has received little empirical attention, such that it is not clear the degree to which opioid taper improves pain responses and outcomes, if at all. Evidence supporting that prescription opioids makes the pain experience worse for chronic pain patients would support a sea change in current practice of chronic opioid therapy.

Studying the direct effects of an opioid taper on pain responses in chronic pain patients is challenging; complicated by the reemergence of pain, variable compliance with taper and concomitant increased use of non-opioid pain medications, a controlled examination of pain responses during and following opioid detoxification is not immediately tenable in this patient population. Thus, funded is a proof-of concept trial to identify and characterize the direct effects of opioid detoxification on experimental pain responses in opioid-dependent patients without chronic pain to establish if, in fact, a notable effect size can be discerned. If supported, these findings will provide a foundation upon which to predict efficacy in patients with the more complicated picture of chronic pain.

Specifically, in a well-characterized sample of men and women seeking addiction treatment in a residential setting, experimental pain responses will be serially described over the course of and for three months following a standard observed opioid (buprenorphine) taper, and compared to those of matched control patients initiated on buprenorphine maintenance therapy. Pain responses will be measured with two valid and reliable experimental pain induction techniques commonly used to measure OIH (cold-pressor, quantitative sensory testing), and subject-level predictors of response identified.

Study Type

Observational

Enrollment (Actual)

15

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
    • Maryland
      • Rockville, Maryland, United States, 20853
        • Avery Road Treatment Center
      • Silver Spring, Maryland, United States, 20910
        • Kolmac Clinic

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 50 years (Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Men and women seeking addiction treatment in a residential or outpatient setting

Description

Inclusion Criteria:

  1. between ages of 18-50
  2. able to provide a positive urine toxicology test for heroin, morphine and/or methadone (and free of other drugs of abuse) upon treatment admission
  3. without known background disease, including chronic or acute pain
  4. otherwise in good physical and mental health, or in the care of a physician who is willing to take responsibility for such treatment
  5. able to understand the purpose and instructions of the study, and provide informed consent as approved by the Western and Georgetown University Institutional Review Boards

Exclusion Criteria:

  1. meet diagnostic criteria for an active substance use disorder other than opioids and nicotine
  2. be acutely psychotic, severely depressed, and/or in need of inpatient psychiatric treatment
  3. have a neurological (i.e. Raynaud's syndrome or symptomatic cold neuropathy) or psychiatric illness that would affect pain responses
  4. have a history of heart disease, stroke, or a pacemaker or uncontrolled high blood pressure. Good cardiovascular health is stipulated to ensure subjects can tolerate the sympathetic nervous system responses associated with the pain induction procedures.
  5. have sensory deficits at pain testing site resulting from medical conditions such as diabetes, alcoholic neuropathy, AIDS neuropathy, severe thyroid, and liver or kidney diseases

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

  • Observational Models: Case-Control
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Opioid Taper
Patients tapering off their buprenorphine treatment
Drug: Buprenorphine
Patients taking buprenorphine to wean off an opiate addiction
Other Names:
  • Suboxone
Opioid Maintenance
Patients starting their buprenorphine treatment
Drug: Buprenorphine
Patients taking buprenorphine to wean off an opiate addiction
Other Names:
  • Suboxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Threshold Response (in seconds) - Cold Pressor Test
Time Frame: 3 months
To compare the effects of opioid taper with initiating buprenorphine maintenance therapy by undergoing experimentally induced cold-pressor test (measured in seconds). Cold pain threshold responses will be compared within-subject in the taper group and between the two groups.
3 months
Pain Tolerance Response (in seconds) - Cold Pressor Test
Time Frame: 3 months
To compare the effects of opioid taper with initiating buprenorphine maintenance therapy by undergoing experimentally induced cold-pressor test (measured in seconds). Cold pain tolerance responses will be compared within-subject in the taper group and between the two groups.
3 months
Pain Threshold Response (in seconds) - Quantitative Sensory Test
Time Frame: 3 months
To compare the effects of opioid taper with initiating buprenorphine maintenance therapy by undergoing experimentally induced quantitative sensory test pain (measured in seconds). Heat pain threshold responses will be compared within-subject in the taper group and between the two groups.
3 months
Pain Tolerance Response (in seconds) - Quantitative Sensory Test
Time Frame: 3 months
To compare the effects of opioid taper with initiating buprenorphine maintenance therapy by undergoing experimentally induced quantitative sensory test pain (measured in seconds). Heat pain tolerance responses will be compared within-subject in the taper group and between the two groups.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in opioid taper
Time Frame: 3 months
A sub-aim of the project is to study how the degree of improvement related to opioid taper in experimental pain responses is related to socio-demographic, psychological, and opioid use history characteristic of the subject.
3 months

Collaborators and Investigators

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

Sponsor

Georgetown University

Collaborators

National Institute on Drug Abuse (NIDA)

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 (Actual)

January 1, 2017

Primary Completion (Actual)

February 28, 2018

Study Completion (Actual)

February 28, 2018

Study Registration Dates

First Submitted

February 8, 2017

First Submitted That Met QC Criteria

February 21, 2017

First Posted (Actual)

February 24, 2017

Study Record Updates

Last Update Posted (Actual)

March 21, 2018

Last Update Submitted That Met QC Criteria

March 19, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-0028
  • U01DA029580 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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