Acute Pain Management in Patients on Opioid Replacement Therapy
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|ClinicalTrials.gov Identifier: NCT03933865|
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : June 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Opioid-use Disorder Pain, Acute||Drug: HYDROmorphone Injectable Solution Drug: Ketamine Drug: Placebos||Phase 1|
Eligible participants will have 8 sessions where they will receive two IM injections.The dose of ketamine will be manipulated (0 mg/kg to 0.4 mg/kg) across sessions. The dose of hydromorphone will either be 0 mg or 8 mg. Therefore, participants will be exposed to ascending doses of ketamine with and without hydromorphone. Order of study medications will be randomized for each participant by an un-blinded statistician and transmitted securely to study pharmacist in charge of medication administration. This study will provide unique information on optimal hydromorphone-ketamine dosing strategies for acute pain management. in buprenorphine maintained patients.
Each session will take place 17 hours after the last buprenorphine dose (trough levels) to control for time since last dose. Sessions will be held on a dedicated unit for human subjects clinical research at Zuckerberg San Francisco General and include two IM injections of study medication given 15 minutes apart by blinded nursing staff. Study sessions will each last approximately 5 hours. Sessions will take place 1-2x weekly and must be separated by at least 72 hours to allow for drug wash-out. QST outcomes will be measured at baseline, as well as 15, 75, 135, and 195 minutes after injection #2 for each session. In addition, abuse liability outcomes will be measured at baseline (if required) and at 15, 75, 135, and 195 minutes after injection #2 for each session.
Blood will be drawn to evaluate baseline buprenorphine /norbuprenorphine levels. Then, PK analyses will be done for ketamine, norketamine and hydromorphone. Blood will be drawn at baseline as well as 15, 75, 135, and 195 minutes after injection #2.
Primary outcome will be analgesia as assessed by QST. The use of various QST measures which assess acute anti-nociception as well as central modification of pain processing will allow us to evaluate whether overall analgesia results from blocking of nociceptor signaling and/or changes to central pain facilitation to better understand the mechanism of ketamine-hydromorphone combinations.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is an outpatient randomized within subject placebo-controlled human laboratory investigation of analgesia (as assessed with quantitative sensory testing) from ketamine alone and in combination with hydromorphone in buprenorphine maintained participants.|
|Masking:||None (Open Label)|
|Masking Description:||Masking: Participant, Investigator, and Outcomes Assessor. The identity of study medication conditions will not be known to investigators, research staff, or patients.|
|Primary Purpose:||Basic Science|
|Official Title:||Acute Pain Management in Patients on Opioid Replacement Therapy|
|Actual Study Start Date :||October 31, 2018|
|Estimated Primary Completion Date :||October 2023|
|Estimated Study Completion Date :||November 2023|
Buprenorphine Maintained Patients
All participants will be maintained on buprenoprhine for the treatment of opioid use disorder. All participants will be exposed to all 8 study drug combinations
Drug: HYDROmorphone Injectable Solution
Hydromorphone will be given via intramuscular injection (8 mg)
Other Name: Dilaudid
Ketamine will be given via intramuscular injection (0.1, 0.2 or 0.4 mg/kg)
Placebo will be normal saline solution given via intramuscular injection.
- peak change in cold pressor tolerance [ Time Frame: 1 day per session ]The amount of time (seconds) a participant can keep hand in cold water bath before pain becomes unbearable. The change will be the highest value after study medications have been administered subtracted from the session baseline.
- peak change in cold pressor threshold [ Time Frame: 1 day per session ]The time (seconds) at which pain first develops after placing hand in cold water bath. The change will be the highest value after study medications have been administered subtracted from the session baseline.
- peak change in conditioned pain modulation (CPM) [ Time Frame: 1 day per session ]Responses to a brief pressure pain stimulus are evaluated alone and then re-assessed during application of a tonic noxious stimulus (hand in water bath) using validated procedures. The peak change in CPM outcome will be a difference in differences score: the largest value of CPM after study medications have been administered subtracted from CPM at baseline
- Peak Drug Liking Visual Analog Scale [ Time Frame: 1 day per session ]The participant positions an arrow along a line (labeled from 0 to 100) using the keypad to indicate his or her answer of how s/he likes the drug(s) at that moment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933865
|Contact: Charlotte Evansfirstname.lastname@example.org|
|Principal Investigator:||D. Andrew Tompkins, MD MHS||University of California, San Francisco|