Opioid-use DisorderPhase 1NCT04473950
The Effect of Chronic Pain on Delay Discounting in Methadone Patients
A Phase 1 study testing Naloxone Hydrochloride in people with Opioid-use Disorder and Chronic Pain Syndrome, run by University of California, San Francisco at 1 site in United States.
Trial summary
The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid-use Disorder, Chronic Pain Syndrome
- What is being tested?
- Naloxone Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2020to 6 Oct 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female adults aged 18-65
- Stable methadone dose (at least 21 days) verified by contacting participant's opioid treatment program
- Understand and speak English
- Urine toxicology screen negative for drugs of abuse and positive for methadone
- Participants must be without signs of intoxication as evidenced by ability to receive full dose of methadone prior to research activities.
- Presence of chronic pain (>3 months) for the Pain group and absence of pain for the No Pain group.
Who cannot join
- Unstable psychiatric illness as assessed by the Mini International Neuropsychiatric Interview (e.g. active suicidal ideation, psychosis)
- Unstable medical illness as assessed by the study's independent medical monitor (e.g. uncontrolled hypertension, recent myocardial infarction, recent stroke, unstable angina) that may be affected by precipitated withdrawal
- Prescription opioid use besides methadone
- Acute pain process unrelated to chronic pain
- Women who are pregnant or lactating
- Known allergy to naloxone
Trial locations and contacts
1 site in 1 country.
United States1 site
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110
About this study
The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD). However, chronic pain can reduce treatment efficacy during medication assisted treatment and is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by which chronic pain may influence the impulsive decision making (e.g., drug relapse) in persons with OUD have not been well characterized. A better understanding is needed of decision-making in this population. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is associated with increases in impulsive decision making in OUD, whether impulsive decision making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the association between withdrawal and impulsive decision making in patients with chronic pain and OUD. An ideal population for this developmental research project are methadone maintained patients, who show high treatment attendance rates and will therefore assure study efficiency and reliable completion.
Read the detailed description
This is an outpatient Phase 1 clinical trial investigating the effect of naloxone precipitated withdrawal on delay discounting. Eligible participants will undergo two experimental sessions presented in random order. One session will involve the measurement of delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo (normal saline) and the other will have the exact same procedures performed after double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid withdrawal measures assessed at baseline and 15 minute intervals after injections. The participant should be back to baseline and free of withdrawal by the end of the study session. Sessions will occur at least 48 hours apart.
- Conditions
- Opioid-use Disorder, Chronic Pain Syndrome
- Being tested
- Naloxone Hydrochloride, Placebo
- Keywords
- delay discounting, pain catastrophizing, impulsivity
- Medical subject headings
- Opioid-Related Disorders, Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naloxone HydrochlorideDrug
Also called Narcan
An intramuscular (IM) injection of naloxone will be given.
PlaceboDrug
An IM injection of 0.9% normal saline will be given.
| Study group | Role | What they receive |
|---|---|---|
| Pain Group | Experimental | Patients with chronic pain who are maintained on methadone for opioid use disorder Receives: Drug: Naloxone Hydrochloride; Drug: Placebo |
| No Pain Group | Placebo comparator | Patients who are maintained on methadone for opioid use disorder but who do not have chronic pain. Receives: Drug: Naloxone Hydrochloride; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delay Discounting of Money Rate (k)
Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k). Delay Discounting of money rate has no units and values can go from 0-infinity. A larger discount rate indicates that a future reward is devalued more, and is associated with more impulsive behavior.
Measured: k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration.
Secondary outcomes (4)
Study Session Peak Pain Visual Analog Scale (VAS)
Current pain level rated on 0-100 VAS. This is the validated pain scale typically used by clinicians in an outpatient or inpatient clinical visit to represent current level of pain. Higher ratings indicate worse pain severity.
Measured: Peak Pain VAS will be the highest rating during each 2 hour study session.
Peak Clinical Opiate Withdrawal Scale (COWS) Rating
The COWS is an 11-item validated clinician administered scale that quantifies level of opioid withdrawal. The range of scores is 0-48, with higher scores indicating greater withdrawal severity. The peak COWS rating will be the highest measurement in the session after study drug administration.
Measured: Peak COWS rating will be the highest rating during each 2 hour study session.
Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
The SOWS is a 16 item validated self-administered scale for grading opioid withdrawal symptoms. The range of scores is 0-64, with higher scores indicating greater withdrawal severity. The peak SOWS rating will be the highest measurement in the session after study drug administration.
Measured: Peak SOWS rating will be the highest rating during each 2 hour study session.
Peak Increase From Baseline Pupil Diameter
Pupil diameter (mm) will be measured via digital pupillometer in standard room lighting at baseline and then throughout the study session after study drug administration. The peak increase from baseline value will be the largest increase from baseline pupil diameter measured after study drug administration.
Measured: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2020
- Study start8 Jan 2020
- Primary completion6 Oct 2022
- Study completion6 Oct 2022
Why it stopped: The COVID-19 Pandemic prevented us from meeting target goals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- D. Andrew Tompkins, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04473950
- Sponsor's protocol ID
- Z-1902
- Other IDs
- R21DA047520
- Status last verified
- Mar 2025
- First submitted
- 12 Jun 2020
- Last updated
- 26 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be made available to the public through presentation at scientific meetings and research publications in peer-reviewed journals. I have routinely kept an open policy to share data with the scientific and medical community upon request, and this policy will be continued with the present project.
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Chronic Pain on Delay Discounting in Methadone Patients
- ClinicalTrials.gov ID
- NCT04473950
- Acronym / sponsor ID
- Z-1902
- Conditions
- Opioid-use Disorder, Chronic Pain Syndrome
- Keywords
- delay discounting, pain catastrophizing, impulsivity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The COVID-19 Pandemic prevented us from meeting target goals.
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Johns Hopkins University, National Institute on Drug Abuse (NIDA)
- Study start
- 8 Jan 2020 (actual)
- Primary completion
- 6 Oct 2022 (actual)
- Study completion
- 6 Oct 2022 (actual)
- First posted
- 16 Jul 2020 (actual)
- Results
- Posted 26 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD). However, chronic pain can reduce treatment efficacy during medication assisted treatment and is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by which chronic pain may influence the impulsive decision making (e.g., drug relapse) in persons with OUD have not been well characterized. A better understanding is needed of decision-making in this population. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is associated with increases in impulsive decision making in OUD, whether impulsive decision making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the association between withdrawal and impulsive decision making in patients with chronic pain and OUD. An ideal population for this developmental research project are methadone maintained patients, who show high treatment attendance rates and will therefore assure study efficiency and reliable completion.
Detailed description
This is an outpatient Phase 1 clinical trial investigating the effect of naloxone precipitated withdrawal on delay discounting. Eligible participants will undergo two experimental sessions presented in random order. One session will involve the measurement of delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo (normal saline) and the other will have the exact same procedures performed after double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid withdrawal measures assessed at baseline and 15 minute intervals after injections. The participant should be back to baseline and free of withdrawal by the end of the study session. Sessions will occur at least 48 hours apart.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study
| Arm | Type | Receives |
|---|---|---|
| Pain Group | Experimental | Drug: Naloxone Hydrochloride, Drug: PlaceboPatients with chronic pain who are maintained on methadone for opioid use disorder |
| No Pain Group | Placebo comparator | Drug: Naloxone Hydrochloride, Drug: PlaceboPatients who are maintained on methadone for opioid use disorder but who do not have chronic pain. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female adults aged 18-65
- Stable methadone dose (at least 21 days) verified by contacting participant's opioid treatment program
- Understand and speak English
- Urine toxicology screen negative for drugs of abuse and positive for methadone
- Participants must be without signs of intoxication as evidenced by ability to receive full dose of methadone prior to research activities.
Key exclusion criteria (6 listed)
- Unstable psychiatric illness as assessed by the Mini International Neuropsychiatric Interview (e.g. active suicidal ideation, psychosis)
- Unstable medical illness as assessed by the study's independent medical monitor (e.g. uncontrolled hypertension, recent myocardial infarction, recent stroke, unstable angina) that may be affected by precipitated withdrawal
- Prescription opioid use besides methadone
- Acute pain process unrelated to chronic pain
- Women who are pregnant or lactating
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 |
|---|---|---|
| Naloxone HydrochlorideAlso: NarcanAn intramuscular (IM) injection of naloxone will be given. | Drug | No Pain Group, Pain Group |
| PlaceboAn IM injection of 0.9% normal saline will be given. | Drug | No Pain Group, Pain Group |
Primary outcome
Delay Discounting of Money Rate (k)
Time frame: k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration.
Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k). Delay Discounting of money rate has no units and values can go from 0-infinity. A larger discount rate indicates that a future reward is devalued more, and is associated with more impulsive behavior.
4 secondary outcomes
Study Session Peak Pain Visual Analog Scale (VAS)
Time frame: Peak Pain VAS will be the highest rating during each 2 hour study session.
Peak Clinical Opiate Withdrawal Scale (COWS) Rating
Time frame: Peak COWS rating will be the highest rating during each 2 hour study session.
Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
Time frame: Peak SOWS rating will be the highest rating during each 2 hour study session.
Peak Increase From Baseline Pupil Diameter
Time frame: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data will be made available to the public through presentation at scientific meetings and research publications in peer-reviewed journals. I have routinely kept an open policy to share data with the scientific and medical community upon request, and this policy will be continued with the present project.
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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 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 Naloxone Hydrochloride in people with Opioid-use Disorder and Chronic Pain Syndrome, 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 6 inclusion and 6 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 26 Mar 2025. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 26 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Delay Discounting of Money Rate (k) (time frame: k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration.). 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 26 Mar 2025.