Study of the Treatment of Experimental Pain in Opioid Dependent Persons on Methadone or Buprenorphine Maintenance - Full Text View

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:

Drug Information available for: Hydromorphone hydrochloride Methadone Hydromorphone Methadone hydrochloride Buprenorphine Buprenorphine hydrochloride

U.S. FDA Resources

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:	May 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

Arms

Assigned Interventions

Methadone Maintenance

Drug: Placebo