Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Acute Pain Management in Patients on Opioid Replacement Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03933865
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This is an outpatient randomized within subject placebo-controlled human laboratory investigation of analgesia (as assessed with quantitative sensory testing; QST) from ketamine alone and in combination with hydromorphone in buprenorphine maintained participants. The goals of this project are to characterize the analgesic, subjective, and physiologic effects of ketamine combined with hydromorphone in patients on buprenorphine maintenance for opioid use disorder.

Condition or disease Intervention/treatment Phase
Opioid-use Disorder Pain, Acute Drug: HYDROmorphone Injectable Solution Drug: Ketamine Drug: Placebos Phase 1

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

Drug: Ketamine
Ketamine will be given via intramuscular injection (0.1, 0.2 or 0.4 mg/kg)

Drug: Placebos
Placebo will be normal saline solution given via intramuscular injection.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females aged 18-60 years of age, inclusive.
  2. Maintained on stable buprenorphine/naloxone (Suboxone®) dose for at least 30 days prior to screening, with total daily dose >=4 mg and <=24 mg (Patients may also be on Zubsolv ® equivalent doses >=2.9 and <=17.2 mg). Participant must agree to stay on this dose for duration of study participation.
  3. Urine toxicology screen negative for drugs of abuse but positive for buprenorphine.
  4. Willing and able to speak, read and understand English.
  5. Able and willing to perform/tolerate QST. Persons who can tolerate cold pressor testing for 5 minutes will be disqualified.
  6. Willing to abstain from analgesic medications (other than buprenorphine) for 24 hours prior to each session.
  7. Written informed consent obtained from participant and ability for participant to comply with the requirements of the study.

Exclusion Criteria:

  1. Current alcohol or sedative-hypnotic use disorder as assessed by the Mini International Neuropsychiatric Interview.
  2. Presence of acute or chronic pain as determined by medical history and physical examination and score of 0 on pain VAS at the start of experimental sessions.
  3. Medical or psychiatric condition known to influence QST (e.g. HIV, peripheral neuropathy, Schizophrenia, Raynaud's syndrome).
  4. Women who are pregnant, breastfeeding, or planning on becoming pregnant during course of trial. Women must be using effective birth control and will receive pregnancy tests before each session.
  5. Poor venous access as an IV catheter will be used for blood draws during sessions.
  6. Past history of psychotic disorder (as assessed through MINI).
  7. Uncontrolled hypertension or clinically significant ECG abnormality.
  8. History of allergy or significant adverse reaction to hydromorphone or ketamine.
  9. Significant contraindication to ketamine use (active psychosis, uncontrolled hypertension, past or current ketamine use disorder, cardiovascular disease, glaucoma, active pulmonary infection or disease).

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Charlotte Evans 415-206-3365 charlotte.evans@ucsf.edu

Locations
Layout table for location information
United States, California
Zuckerberg San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Charlotte Evans    415-206-3365    charlotte.evans@ucsf.edu   
Contact: D. Andrew Tompkins    415-206-3645    david.tompkins@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
Investigators
Layout table for investigator information
Principal Investigator: D. Andrew Tompkins, MD MHS University of California, San Francisco
Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03933865    
Other Study ID Numbers: Z-1701
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
buprenorphine
quantitative sensory testing
cold pressor
abuse liability
ketamine
hydromorphone
Additional relevant MeSH terms:
Layout table for MeSH terms
Acute Pain
Pain
Neurologic Manifestations
Ketamine
Hydromorphone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics