Clinical trial NCT03063905: The Effects of Opioid Taper on Opioid-Induced Hyperalgesia
Official title: The Effects of Opioid Taper on Opioid-Induced Hyperalgesia
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Buprenorphine
Pain
Keywords: Opioid related disorders
Narcotic abuse
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2017-02-24
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women seeking addiction treatment in a residential or outpatient setting

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain Threshold Response (in seconds) - Cold Pressor Test
timeFrame: 3 months
measure: Pain Tolerance Response (in seconds) - Cold Pressor Test
timeFrame: 3 months
measure: Pain Threshold Response (in seconds) - Quantitative Sensory Test
timeFrame: 3 months
measure: Pain Tolerance Response (in seconds) - Quantitative Sensory Test
timeFrame: 3 months
Secondary outcomes:
measure: Improvement in opioid taper
timeFrame: 3 months
Other outcomes:
Locations:
city: Rockville
country: United States
facility: Avery Road Treatment Center
state: Maryland
city: Silver Spring
country: United States
facility: Kolmac Clinic
state: Maryland
Study officials:
affiliation: Georgetown University
name: Peggy Compton, RN, PhD
role: PRINCIPAL_INVESTIGATOR
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