Back to resultsAcute Pain Management in Patients on Opioid Replacement Therapy
Primary Purpose
Opioid-use Disorder, Pain, Acute
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HYDROmorphone Injectable Solution
Ketamine
Placebos
Sponsored by
About this trial
This is an interventional basic science trial for Opioid-use Disorder focused on measuring buprenorphine, quantitative sensory testing, cold pressor, abuse liability, ketamine, hydromorphone
Eligibility Criteria
Inclusion Criteria:
- Males and females aged 18-60 years of age, inclusive.
- 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.
- Urine toxicology screen negative for drugs of abuse but positive for buprenorphine.
- Willing and able to speak, read and understand English.
- Able and willing to perform/tolerate QST. Persons who can tolerate cold pressor testing for 5 minutes will be disqualified.
- Willing to abstain from analgesic medications (other than buprenorphine) for 24 hours prior to each session.
- Written informed consent obtained from participant and ability for participant to comply with the requirements of the study.
Exclusion Criteria:
- Current alcohol or sedative-hypnotic use disorder as assessed by the Mini International Neuropsychiatric Interview.
- 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.
- Medical or psychiatric condition known to influence QST (e.g. HIV, peripheral neuropathy, Schizophrenia, Raynaud's syndrome).
- 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.
- Poor venous access as an IV catheter will be used for blood draws during sessions.
- Past history of psychotic disorder (as assessed through MINI).
- Uncontrolled hypertension or clinically significant ECG abnormality.
- History of allergy or significant adverse reaction to hydromorphone or ketamine.
- Significant contraindication to ketamine use (active psychosis, uncontrolled hypertension, past or current ketamine use disorder, cardiovascular disease, glaucoma, active pulmonary infection or disease).
Sites / Locations
- Zuckerberg San Francisco General Hospital
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Buprenorphine Maintained Patients
Arm Description
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
Outcomes
Primary Outcome Measures
peak change in cold pressor tolerance
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
peak change in cold pressor threshold
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)
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
Full Information
NCT ID
NCT03933865
First Posted
December 4, 2018
Last Updated
October 6, 2022
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT03933865
Brief Title
Acute Pain Management in Patients on Opioid Replacement Therapy
Official Title
Acute Pain Management in Patients on Opioid Replacement Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
The COVID-19 pandemic and recruitment difficulties prompted the investigators to terminate study early.
Study Start Date
October 31, 2018 (Actual)
Primary Completion Date
February 24, 2022 (Actual)
Study Completion Date
February 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-use Disorder, Pain, Acute
Keywords
buprenorphine, quantitative sensory testing, cold pressor, abuse liability, ketamine, hydromorphone
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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.
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Buprenorphine Maintained Patients
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
HYDROmorphone Injectable Solution
Other Intervention Name(s)
Dilaudid
Intervention Description
Hydromorphone will be given via intramuscular injection (8 mg)
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Description
Ketamine will be given via intramuscular injection (0.1, 0.2 or 0.4 mg/kg)
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Placebo will be normal saline solution given via intramuscular injection.
Primary Outcome Measure Information:
Title
peak change in cold pressor tolerance
Description
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.
Time Frame
1 day per session
Secondary Outcome Measure Information:
Title
peak change in cold pressor threshold
Description
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.
Time Frame
1 day per session
Title
peak change in conditioned pain modulation (CPM)
Description
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
Time Frame
1 day per session
Other Pre-specified Outcome Measures:
Title
Peak Drug Liking Visual Analog Scale
Description
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.
Time Frame
1 day per session
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females aged 18-60 years of age, inclusive.
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.
Urine toxicology screen negative for drugs of abuse but positive for buprenorphine.
Willing and able to speak, read and understand English.
Able and willing to perform/tolerate QST. Persons who can tolerate cold pressor testing for 5 minutes will be disqualified.
Willing to abstain from analgesic medications (other than buprenorphine) for 24 hours prior to each session.
Written informed consent obtained from participant and ability for participant to comply with the requirements of the study.
Exclusion Criteria:
Current alcohol or sedative-hypnotic use disorder as assessed by the Mini International Neuropsychiatric Interview.
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.
Medical or psychiatric condition known to influence QST (e.g. HIV, peripheral neuropathy, Schizophrenia, Raynaud's syndrome).
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.
Poor venous access as an IV catheter will be used for blood draws during sessions.
Past history of psychotic disorder (as assessed through MINI).
Uncontrolled hypertension or clinically significant ECG abnormality.
History of allergy or significant adverse reaction to hydromorphone or ketamine.
Significant contraindication to ketamine use (active psychosis, uncontrolled hypertension, past or current ketamine use disorder, cardiovascular disease, glaucoma, active pulmonary infection or disease).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
D. Andrew Tompkins, MD MHS
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zuckerberg San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Acute Pain Management in Patients on Opioid Replacement Therapy
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