Increased Sensitivity to Pain Caused by Opioids in People Who Have Abused Prescription Opioids

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Georgetown University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Peggy Compton, Georgetown University
ClinicalTrials.gov Identifier:
NCT01821430
First received: March 27, 2013
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

Managing pain in patients who abuse prescription opioids presents many challenges, including the development of opioid-induced hyperalgesia (OIH). Hyperalgesia is a condition in which something that usually feels slightly painful is perceived as something very painful. The proposed study will test the efficacy of the well-known neurological medication pregabalin to diminish OIH and chronic pain in persons who are in Suboxone (buprenorphine) treatment for prescription drug abuse.


Condition Intervention Phase
Chronic Pain
Drug: Pregabalin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Opioid-Induced Hyperalgesia in Prescription Opioid Abusers: Effects of Pregabalin

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Improved Pain Response, threshold and tolerance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    To test the efficacy of PGB, compared to placebo, to diminish OIH, as evidenced by improved pain responses (threshold and tolerance) to experimentally induced cold-pressor pain, in a well-described sample of POA patients with chronic pain and on buprenorphine therapy.

    • Pain Threshold: On the CP assay, pain threshold is operationalized as the number of seconds after the onset of the painful stimulus when a painful sensation is first detected. Subjects will indicate threshold by saying "Pain."
    • Pain Tolerance: On the CP assay, pain tolerance is operationalized as the number of seconds after the onset of the painful stimulus when the painful sensation is subjectively intolerable. Subjects will indicate tolerance by removing their arm from the ice bath.


Secondary Outcome Measures:
  • Improvement in pain severity and daily functionality [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    To test the efficacy of PGB, compared to placebo, to diminish chronic pain, as evidenced by improvements in pain severity and functionality in a well-described sample of POA patients with chronic pain and on buprenorphine therapy.

    Pain Severity will be measured with The McGill Pain Questionnaire. Daily Functionality will be measured with the Brief Pain Inventory



Estimated Enrollment: 150
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pregabalin
Pregabalin 400mg / Day
Drug: Pregabalin
Titration of intervention will begin with 50mg PO BID x 2 days, then 100mg PO BID x 2 days, then 150mg PO BID X 2 days, then on day 7 full dose of Pregabalin 400mg PO QD for six weeks
Other Name: Lyrica
Placebo Comparator: Placebo Control
Placebo Tablet
Drug: Placebo
Placebo group will follow the same titration as the pregabalin group

Detailed Description:

The clinical management of pain in prescription opioid abusers presents a challenge to the health care professional. Investigators have novel pilot data showing that the GABA-agonist gabapentin (GPN) significantly decreases opioid-induced hyperalgesia (OIH) in methadone patients (Compton et al., 2009), providing the first empirical evidence of a pharmacotherapy for OIH in opioid abusers. The work of Gore and colleagues (2011) showed that pregabalin (PGB), a GABA analogue succeeding GPN, was shown to decrease opioid use in patients with neuropathic pain in patients, suggesting an anti-hyperalgesia effect not observed in the matched cohort receiving GPN. The proposed research will comprehensively evaluate the efficacy of PGB in treating opioid-induced hyperalgesia (OIH) in a well-described population of prescription opioid abusers (POAs) with chronic pain and on Suboxone (buprenorphine) therapy. A pressing need for such investigation is presented by the rising number of POAs presenting for treatment (SAMHSA, 2010; 2011), and for whom, chronic pain is a common co-morbidity. The proposed work is anticipated to provide vital and timely information on the efficacy of PGB in the treatment of OIH in prescription opioid abusers on Suboxone therapy.

Following recruitment and screening, 75 subjects assigned to the active medication group will receive pregabalin 400 mg/day, a dose well-within published guidelines of 300-600 mg/day for the treatment of neuropathic pain (http://www.pfizerpro.com/hcp/lyrica/phndosing). During the first week of treatment, subjects will be quickly titrated up to the assigned daily PGB dose of 400 mg/day PO (50mg BID x 2 days; 100mg BID x 2 days; 150mg BID x 2 days, with full dosage of 400mg administered on day 7 ), or maximum dose tolerated) for six weeks. 75 subjects will be assigned to receive matched and undergo identical titration and study activities under double-blind conditions. Study staff will evaluate subjects daily by phone during titration; thereafter they will be seen weekly at study sessions. Tapering of medication will begin at the end of week 6. The severity of chronic pain will be measured at each time point using two standardized self report tools which report on pain severity (McGill Pain Questionnaire) and pain-related disability (Brief Pain Inventory). Opioid-induced hyperalgesia will be measured at each time point using a standardized cold pressor trial, and performance at baseline will be compared to performance following PGB/placebo administration over time.

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be between the ages of 21 and 70 years of age.
  • Have a DSM-IVR diagnosis (used through 10/1/2014) of prescription opioid abuse or dependence disorder or a DSM-5 diagnosis of opioid use disorder.
  • Be enrolled and compliant in buprenorphine treatment and on a stable dose of buprenorphine (6-24mg/day) x at least 10 days.
  • Have provided random urine samples absent of any non-prescribed drugs of abuse x 2 months
  • Screening cold-pressor pain tolerance < 70 seconds
  • Have a medically-diagnosed chronic pain problem.
  • Be otherwise in good physical health or in the case of a medical condition needing ongoing treatment, be in the care of a physician who is willing to take responsibility for such treatment. The same conditions apply in cases of patients with a psychiatric disorder needing ongoing treatment.
  • Be agreeable to and capable of signing an informed consent.

Exclusion Criteria:

  • Have known sensitivity to pregabalin.
  • Be substance dependent on alcohol, benzodiazepine, methamphetamine, cocaine or other drugs of abuse (except nicotine).
  • Have any acute medical condition that would make participation medically hazardous, (e.g., acute hepatitis, unstable cardiovascular disease, liver or renal disease) or have liver enzyme values (AST or ALT) greater than 5 times normal range.
  • Be acutely psychotic, severely depressed and in need of inpatient treatment, or an immediate suicide risk.
  • Have a neurological or psychiatric illness (i.e., schizophrenia, Raynaud's disease, urticaria, stroke) that would affect pain responses.
  • Be currently taking opioid analgesic medication for a painful condition on a regular basis.
  • Be a nursing or pregnant female. Female of childbearing potential must agree to use a medically acceptable method of birth control, (e.g. oral contraceptives, barrier (diaphragm or condom) with or without spermicide, levonorgestrel implant, intra-uterine progesterone contraceptives system, medroxyprogesterone acetate contraceptive injection) or to complete abstinence. Females who become pregnant during the course of the study will be dropped from the study.
  • Have a current or past history of high blood pressure, heart disease, stroke or currently have a pacemaker.
  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: NCT01821430

Contacts
Contact: Kristen Willard, MS 202-687-1788 willardk@georgetown.edu
Contact: Peggy Compton, RN, PhD 202-687-3157 pcompton@georgetown.edu

Locations
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Kristen Willard, MS    202-687-1788    willardk@georgetown.edu   
Contact: Peggy Compton, RN, PhD    202-687-3157    pcompton@georgetown.edu   
Principal Investigator: Peggy Compton, RN, PhD         
Sponsors and Collaborators
Georgetown University
Investigators
Principal Investigator: Peggy Compton, RN, PhD Georgetown University
  More Information

Publications:

Responsible Party: Peggy Compton, Professor and Associate Dean, Georgetown University
ClinicalTrials.gov Identifier: NCT01821430     History of Changes
Other Study ID Numbers: Pro00000669, U01DA029580
Study First Received: March 27, 2013
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Georgetown University:
Chronic Pain
Narcotic Abuse
Opioid related disorders
Opiate substitution treatment
Buprenorphrine
Pregabalin

Additional relevant MeSH terms:
Chronic Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014