Study of the Treatment of Experimental Pain in Opioid Dependent Persons on Methadone or Buprenorphine Maintenance

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Johns Hopkins University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
D. Andrew Tompkins, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01642030
First received: July 9, 2012
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

Pain is very common in persons with a history of addiction, but few studies have examined the best treatment of pain in this population. This is a study to determine the pain relief provided by intravenous hydromorphone (Dilaudid) or buprenorphine given to persons maintained on stable doses of methadone or buprenorphine. Experimental sessions will require overnight stays on a residential research unit. In these sessions, persons will be exposed to standard experimental pain techniques at baseline and then rate the relief (if any) provided by the study medication when exposed to the same techniques. Persons will be asked to participate in 2 or 3 sessions, each separated by at least 7 days.


Condition Intervention Phase
Opioid Dependence
Pain
Addiction
Drug: Placebo
Drug: Hydromorphone
Drug: Buprenorphine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Analgesic Effects and Abuse Liability of Intravenous Hydromorphone and Buprenorphine in Pain-free Opioid Dependent Participants

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Cold pressor test. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    The participant places a hand up to the wrist in a circulating water bath maintained at approximately 4 degrees Celsius (up to 5 minutes). The time at which pain develops is the threshold. The time a volunteer's hand remains underwater before pain is unbearable is tolerance.

  • Innocuous stimulation. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    Participants' thresholds for warmth and touch sensations will be measured bilaterally on the ventral forearm using the FDA approved Medoc thermal stimulator (Ramat Yishai, Israel) and calibrated Von Frey filaments.

  • Pressure pain. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    An electronic algometer (Somedic; Horby, Sweden) with a 1cm2 hard rubber probe will be used to assess responses to noxious mechanical pressure on the trapezius and forearm. Pressure is gradually increased at a constant rate (30kPA/sec); the average threshold and tolerance across 2 trials will be calculated.

  • Thermal pain. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    All contact heat stimuli will be delivered using the FDA approved Medoc thermal stimulator (Ramat Yishai, Israel) on the dorsal forearm or dorsum of the foot. The thermode's temperature gradually increases (0.5oC/sec) until no longer tolerated (max 51 degrees Celsius). The average threshold and tolerance across 2 trials will be calculated.

  • Temporal summation. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    Temporal summation involves rapidly applying a series of identical noxious stimuli in the same area to determine the increase in pain across trials. For temporal summation of thermal pain, 3 sequences of 10 heat pulses each from the FDA approved Medoc thermal stimulator (Ramat Yishai, Israel) will be applied to the dorsal forearm.

  • Diffuse noxious inhibitory controls (DNIC). [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    DNIC refers to the phenomenon of one noxious stimulus inhibiting the pain of a second noxious stimulus. Baseline responses to a brief painful stimulus (e.g., algometer on right trapezius) are evaluated and then re-assessed during application of a tonic noxious stimulus (e.g., cold pressor test with left hand).


Secondary Outcome Measures:
  • Visual analog scales (VAS) of subjective drug effects. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    VAS are single item questions that assessed subjective drug effects at the time of scale completion. Ratings are entered into a computer by the participant positioning an arrow along a 100 mm line marked at either end with "none" (0) and "extremely" (100).

  • Pupil diameter. [ Time Frame: This will be measured at baseline and every 15 minutes during experimental pain testing. Testing will occur during 10 hours of each 40-hour session. Sessions will be separated by at least 7 days. ] [ Designated as safety issue: No ]
    This will be assessed with a digital pupilometer (Neuroptics, Inc.) in constant room lighting.

  • Number of participants with adverse events. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: Yes ]
  • Profile of Mood States. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    This scale consists of 72 adjectives commonly used to describe momentary mood states. Participants rate from 0 (not at all) to 5 (extremely).

  • Vital Signs. [ Time Frame: This will be measured at baseline and every 15 minutes during experimental pain testing. Testing will occur during 10 hours of each 40-hour session. Sessions will be separated by at least 7 days. ] [ Designated as safety issue: Yes ]
    These include blood pressure, pulse, respiration rate, oxygen saturation, and skin temperature.

  • Trait pain catastrophizing. [ Time Frame: This will be measured once during the screening visit. ] [ Designated as safety issue: No ]
    Pain catastrophizing scale (PCS) will be done at screening to measure trait levels of catastrophizing.

  • Situational pain catastrophizing. [ Time Frame: This will be measured 7 times during each 40-hour session. On average, all sessions will be completed within 4 weeks. ] [ Designated as safety issue: No ]
    This construct compromises the sum of 6 questions measuring the 3 primary dimensions of catastrophizing: rumination, magnification, and helplessness.


Estimated Enrollment: 100
Study Start Date: August 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Methadone Maintenance Drug: Placebo
Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other Name: Normal Saline
Drug: Hydromorphone
Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other Name: Dilaudid
Buprenorphine Maintenance Drug: Placebo
Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other Name: Normal Saline
Drug: Hydromorphone
Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other Name: Dilaudid
Drug: Buprenorphine
Intravenous injection of approximately 5 mL administered via slow push over 5 minutes. Given 4 injections during the session with each injection separated by 1.5 hours.
Other Names:
  • Suboxone
  • Subutex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age 18-55;
  2. diagnosis of opioid dependence
  3. urine toxicology negative for drugs of abuse but positive for opioid maintenance agent;
  4. stable buprenorphine (12-16 mg) or methadone (80-100 mg) dose for the past 30 days;
  5. absence of acute/chronic pain;
  6. able and willing to perform/tolerate pain procedures;
  7. able to communicate in English.

Exclusion Criteria:

  1. current illicit substance use at screening or during trial (including cannabis use);
  2. current diagnosis of alcohol dependence;
  3. acute or chronic pain;
  4. medical or psychiatric condition known to influence pain testing;
  5. current use of prescribed or over the counter analgesic agents;
  6. previous allergic reaction to hydromorphone or buprenorphine;
  7. women who are pregnant, lactating or planning to get pregnant during the course of the trial.
  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: NCT01642030

Contacts
Contact: Jessica Harras 410-550-9494 jharras2@jhmi.edu
Contact: D. Andrew Tompkins, M.D. 410-550-5953

Locations
United States, Maryland
Behavioral Pharmacology Research Unit Recruiting
Baltimore, Maryland, United States, 21224
Contact: Jessica Harras    410-550-9494    jharras2@jhmi.edu   
Principal Investigator: D. Andrew Tompkins, M.D.         
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: D. Andrew Tompkins, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: D. Andrew Tompkins, MD, Assistant Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01642030     History of Changes
Other Study ID Numbers: 1203, K23DA029609
Study First Received: July 9, 2012
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Quantitative sensory testing
Cold pressor test
Opioid dependence
Methadone maintenance
Buprenorphine maintenance
Abuse liability
DNIC
Temporal Summation

Additional relevant MeSH terms:
Behavior, Addictive
Opioid-Related Disorders
Compulsive Behavior
Impulsive Behavior
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Buprenorphine
Hydromorphone
Methadone
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
Narcotic Antagonists
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 31, 2014