Opioid-use DisorderPhase 1NCT03933865
Acute Pain Management in Patients on Opioid Replacement Therapy
A Phase 1 study testing HYDROmorphone Injectable Solution and Ketamine in people with Opioid-use Disorder and Pain, Acute, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Opioid-use Disorder, Pain, Acute
- What is being tested?
- HYDROmorphone Injectable Solution and Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2018to 24 Feb 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110
About this study
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.
Read the 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.
- Conditions
- Opioid-use Disorder, Pain, Acute
- Being tested
- HYDROmorphone Injectable Solution, Ketamine, Placebos
- Keywords
- buprenorphine, quantitative sensory testing, cold pressor, abuse liability, ketamine, hydromorphone
- Medical subject headings
- Opioid-Related Disorders, Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HYDROmorphone Injectable SolutionDrug
Also called Dilaudid
Hydromorphone will be given via intramuscular injection (8 mg)
KetamineDrug
Ketamine will be given via intramuscular injection (0.1, 0.2 or 0.4 mg/kg)
PlacebosDrug
Placebo will be normal saline solution given via intramuscular injection.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: HYDROmorphone Injectable Solution; Drug: Ketamine; Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 day per session
Secondary outcomes (2)
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.
Measured: 1 day per session
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
Measured: 1 day per session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start31 Oct 2018
- Primary completion24 Feb 2022
- Study completion24 Feb 2022
Why it stopped: The COVID-19 pandemic and recruitment difficulties prompted the investigators to terminate study early.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- D. Andrew Tompkins, MD MHS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03933865
- Sponsor's protocol ID
- Z-1701
- Status last verified
- Oct 2022
- First submitted
- 4 Dec 2018
- Last updated
- 10 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Pain Management in Patients on Opioid Replacement Therapy
- ClinicalTrials.gov ID
- NCT03933865
- Acronym / sponsor ID
- Z-1701
- Conditions
- Opioid-use Disorder, Pain, Acute
- Keywords
- buprenorphine, quantitative sensory testing, cold pressor, abuse liability, ketamine, hydromorphone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The COVID-19 pandemic and recruitment difficulties prompted the investigators to terminate study early.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 31 Oct 2018 (actual)
- Primary completion
- 24 Feb 2022 (actual)
- Study completion
- 24 Feb 2022 (actual)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine Maintained Patients | Other | Drug: HYDROmorphone Injectable Solution, Drug: Ketamine, Drug: PlacebosAll participants will be maintained on buprenoprhine for the treatment of opioid use disorder. All participants will be exposed to all 8 study drug combinations |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HYDROmorphone Injectable SolutionAlso: DilaudidHydromorphone will be given via intramuscular injection (8 mg) | Drug | Buprenorphine Maintained Patients |
| KetamineKetamine will be given via intramuscular injection (0.1, 0.2 or 0.4 mg/kg) | Drug | Buprenorphine Maintained Patients |
| PlacebosPlacebo will be normal saline solution given via intramuscular injection. | Drug | Buprenorphine Maintained Patients |
Primary outcome
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.
2 secondary outcomes
peak change in cold pressor threshold
Time frame: 1 day per session
peak change in conditioned pain modulation (CPM)
Time frame: 1 day per session
Results and safety
The study was stopped early (reason given: The COVID-19 pandemic and recruitment difficulties prompted the investigators to terminate study early.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
D. Andrew Tompkins, MD MHS principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HYDROmorphone Injectable Solution and Ketamine in people with Opioid-use Disorder and Pain, Acute, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The COVID-19 pandemic and recruitment difficulties prompted the investigators to terminate study early.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
peak change in cold pressor tolerance (time frame: 1 day per session). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2022.