Acute Pain Management in Patients on Opioid Replacement Therapy

NCT03933865 | Terminated Phase 1 FDA Drug

• 1 other identifier: Z-1701
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid-use Disorder; Pain, Acute

Keywords

buprenorphine; quantitative sensory testing; cold pressor; abuse liability; ketamine; hydromorphone

Outcome Measures

Primary Outcomes (1)

• 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.

  1 day per session

Secondary Outcomes (2)

• peak change in cold pressor threshold

  1 day per session

• peak change in conditioned pain modulation (CPM)

  1 day per session

Other Outcomes (1)

• Peak Drug Liking Visual Analog Scale

  1 day per session

Study Arms (1)

Buprenorphine Maintained Patients

OTHER

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; Drug: Ketamine; Drug: Placebos

Interventions

HYDROmorphone Injectable Solution DRUG

Hydromorphone will be given via intramuscular injection (8 mg)

Also known as: Dilaudid

Buprenorphine Maintained Patients

Ketamine DRUG

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

Buprenorphine Maintained Patients

Placebos DRUG

Placebo will be normal saline solution given via intramuscular injection.

Buprenorphine Maintained Patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Acute Pain

Interventions

Hydromorphone; Ketamine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• D. Andrew Tompkins, MD MHS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Masking: Participant, Investigator, and Outcomes Assessor. The identity of study medication conditions will not be known to investigators, research staff, or patients.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: May 1, 2019
• Study Start: October 31, 2018
• Primary Completion: February 24, 2022
• Study Completion: February 24, 2022
• Last Updated: October 10, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)