Opioid Use DisorderPhase 2/3NCT05459402
Divided or Single Exposure (DOSE) Study
A Phase 2/3 study testing Methadone (100% dose) and Methadone (50% dose) in people with Opioid Use Disorder and Chronic Pain, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
This study will evaluate whether once versus twice daily dosing of methadone will be an effective method for managing comorbid pain and opioid use disorder. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Opioid Use Disorder, Chronic Pain, Methadone
- What is being tested?
- Methadone (100% dose) and Methadone (50% dose)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2023to 1 Jun 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years of age or older
- Currently receiving methadone for treatment of OUD for >90 days and have been consuming the same dose for >30 days
- Have previously received a take-home dose of methadone as part of routine care
- Willing to comply with study schedule
- Report pain (specific definition blinded)
- Have a cellular phone or be willing to carry phone provided by the study during one phase of the study
Who cannot join
- Pregnant
- Presence of acute medical problem that requires immediate and intense medical management
- Presence of a serious and unstable mental illness that interferes with provision of voluntary informed consent and/or adherence to study visits
- Plans to leave methadone treatment during the study period
- Maintained on a dose of methadone that would prevent effective splitting of doses
- Currently receiving split doses of methadone
- Currently receiving treatment for pain for which the split-dosing of methadone is judged by medical staff to be contraindicated or otherwise interfere with study conduct or integrity
- Does not meet criteria for mild-severe disability (definition blinded)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Addiction Treatment Services (ATS)
Baltimore, Maryland, 21224
Denis Antoine, MD
About this study
Official title: Divided or Single Exposure (DOSE) Study: Randomized Controlled Trial for Pain in Persons Receiving Methadone Treatment
This study will evaluate whether once versus twice daily dosing of methadone will be an effective method for managing comorbid pain and opioid use disorder.
Read the detailed description
This study follows a successfully completed project (NCT03254043) to now pursue the investigators overarching goal of optimizing methadone dosing as a method for managing comorbid chronic pain and opioid use disorder (OUD) among persons receiving methadone for the treatment of OUD. Up to 62% of persons maintained on methadone for OUD experience clinically significant pain, versus 31% in the general population. Pain in methadone-maintained persons (MMP) is associated with poor OUD treatment outcomes and severe distress. No effective treatment for comorbid pain and OUD currently exists; though preclinical and human data suggest divided methadone dosing may be a more optimal strategy for managing pain than once daily dosing, this has never been empirically examined. This study will evaluate an intervention for comorbid chronic pain among MMP using a Phase II double-blind, randomized, placebo-controlled comparison of treatment as usual (TAU) versus split daily methadone dosing for 12-weeks. Methadone will be remotely managed via an electronic pillbox. Outcomes will include weekly assessments of pain and OUD outcomes, ecological momentary assessment of pain before and after dosing, and point-prevalence measures of laboratory-induced pain to explore mechanism of effects. If effective, this approach could transform the care of MMP with pain because it would be feasible to implement within the operational structure of a methadone clinic and would impose low provider burden. Results could provide a high magnitude treatment for the substantial number of MMP who experience daily pain with no reliable form of treatment.
- Conditions
- Opioid Use Disorder, Chronic Pain, Methadone
- Being tested
- Methadone (100% dose), Methadone (50% dose)
- Medical subject headings
- Opioid-Related Disorders, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methadone (100% dose)Drug
Methadone for the treatment of opioid use disorder
Methadone (50% dose)Drug
Methadone for the treatment of opioid use disorder
| Study group | Role | What they receive |
|---|---|---|
| Treatment as Usual (TAU) | Active comparator | Participants in treatment as usual group will receive 100% active methadone in AM + placebo in PM. Receives: Drug: Methadone (100% dose) |
| Split-dosing | Experimental | Participants in split dosing group will receive 50% active methadone + placebo twice daily. Receives: Drug: Methadone (50% dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in worst pain rating- past 24 hour as assessed by the Brief Pain Inventory scale
Using the Brief Pain Inventory rating of "Worst Pain" in the past 24 hours, rated on a scale of 1-10, collected once weekly during weeks 1 through 12 of the intervention.
Measured: Week 1 up to week 12
Secondary outcomes (3)
Change in Pain Tolerance Latency
Time in seconds (0-300) to removal of hand from cold pressor measure of laboratory-induced pain, collected point-prevalence during weeks 1, 6, and 12 of the intervention.
Measured: Weeks 1, 6, and 12
Change in Pain Interference- past 7 days as assessed by Pain-related Disability Scale Total Score
Past 7 day Pain-related Disability Scale Total Score (range 0-70), collected once weekly during weeks 1 through 12 of the intervention.
Measured: Week 1 up to 12
Change in Opioid Withdrawal Severity- past 24 hours as assessed by the Subjective Opioid Withdrawal Scale
Past 24 hour total score (range 0-64) for the Subjective Opioid Withdrawal Scale (SOWS), collected once weekly during weeks 1 through 12 of the intervention.
Measured: Week 1 up to 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2022
- Study start21 Feb 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be enrolled for a 14-week Phase II between-group intervention period followed by a 6-month follow-up period with once monthly visits. All participants will be transitioned from liquid to tablet methadone within a 1 to 2-week period before being randomized to treatment as usual versus split daily methadone dosing for a 12-week period. Participants will complete monthly follow-up visits during months 4 - 9.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Kelly E Dunn, PhD, M.B.A., Principal investigator, University of MarylandDenis Antoine, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05459402
- Sponsor's protocol ID
- IRB00318642
- Other IDs
- 1R01DA056045, 1R01DA056045-01
- Status last verified
- Jan 2026
- First submitted
- 12 Jul 2022
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McKendrick G, Davis W, Sklar M, Brown N, Pattillo E, Finan PH, Antoine D, Walters V, Dunn KE. The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder. Subst Use Addctn J. 2025 Jan;46(1):197-200. doi: 10.1177/29767342241239167. Epub 2024 Mar 25.
PubMed 38528704
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Divided or Single Exposure (DOSE) Study: Randomized Controlled Trial for Pain in Persons Receiving Methadone Treatment
- ClinicalTrials.gov ID
- NCT05459402
- Acronym / sponsor ID
- IRB00318642
- Conditions
- Opioid Use Disorder, Chronic Pain, Methadone
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 21 Feb 2023 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 15 Jul 2022 (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 study will evaluate whether once versus twice daily dosing of methadone will be an effective method for managing comorbid pain and opioid use disorder.
Detailed description
This study follows a successfully completed project (NCT03254043) to now pursue the investigators overarching goal of optimizing methadone dosing as a method for managing comorbid chronic pain and opioid use disorder (OUD) among persons receiving methadone for the treatment of OUD. Up to 62% of persons maintained on methadone for OUD experience clinically significant pain, versus 31% in the general population. Pain in methadone-maintained persons (MMP) is associated with poor OUD treatment outcomes and severe distress. No effective treatment for comorbid pain and OUD currently exists; though preclinical and human data suggest divided methadone dosing may be a more optimal strategy for managing pain than once daily dosing, this has never been empirically examined. This study will evaluate an intervention for comorbid chronic pain among MMP using a Phase II double-blind, randomized, placebo-controlled comparison of treatment as usual (TAU) versus split daily methadone dosing for 12-weeks. Methadone will be remotely managed via an electronic pillbox. Outcomes will include weekly assessments of pain and OUD outcomes, ecological momentary assessment of pain before and after dosing, and point-prevalence measures of laboratory-induced pain to explore mechanism of effects. If effective, this approach could transform the care of MMP with pain because it would be feasible to implement within the operational structure of a methadone clinic and would impose low provider burden. Results could provide a high magnitude treatment for the substantial number of MMP who experience daily pain with no reliable form of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be enrolled for a 14-week Phase II between-group intervention period followed by a 6-month follow-up period with once monthly visits. All participants will be transitioned from liquid to tablet methadone within a 1 to 2-week period before being randomized to treatment as usual versus split daily methadone dosing for a 12-week period. Participants will complete monthly follow-up visits during months 4 - 9.
| Arm | Type | Receives |
|---|---|---|
| Treatment as Usual (TAU) | Active comparator | Drug: Methadone (100% dose)Participants in treatment as usual group will receive 100% active methadone in AM + placebo in PM. |
| Split-dosing | Experimental | Drug: Methadone (50% dose)Participants in split dosing group will receive 50% active methadone + placebo twice daily. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged 18 years of age or older
- Currently receiving methadone for treatment of OUD for >90 days and have been consuming the same dose for >30 days
- Have previously received a take-home dose of methadone as part of routine care
- Willing to comply with study schedule
- Report pain (specific definition blinded)
Key exclusion criteria (8 listed)
- Pregnant
- Presence of acute medical problem that requires immediate and intense medical management
- Presence of a serious and unstable mental illness that interferes with provision of voluntary informed consent and/or adherence to study visits
- Plans to leave methadone treatment during the study period
- Maintained on a dose of methadone that would prevent effective splitting of doses
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 |
|---|---|---|
| Methadone (100% dose)Methadone for the treatment of opioid use disorder | Drug | Treatment as Usual (TAU) |
| Methadone (50% dose)Methadone for the treatment of opioid use disorder | Drug | Split-dosing |
Primary outcome
Change in worst pain rating- past 24 hour as assessed by the Brief Pain Inventory scale
Time frame: Week 1 up to week 12
Using the Brief Pain Inventory rating of "Worst Pain" in the past 24 hours, rated on a scale of 1-10, collected once weekly during weeks 1 through 12 of the intervention.
3 secondary outcomes
Change in Pain Tolerance Latency
Time frame: Weeks 1, 6, and 12
Change in Pain Interference- past 7 days as assessed by Pain-related Disability Scale Total Score
Time frame: Week 1 up to 12
Change in Opioid Withdrawal Severity- past 24 hours as assessed by the Subjective Opioid Withdrawal Scale
Time frame: Week 1 up to 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2026.
- Derived from this study: PubMed 38528704McKendrick G, Davis W, Sklar M, Brown N, Pattillo E, Finan PH, Antoine D, Walters V, Dunn KE. The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder. Subst Use Addctn J. 2025 Jan;46(1):197-200. doi: 10.1177/29767342241239167. Epub 2024 Mar 25.
- 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.
Kelly E Dunn, PhD, M.B.A. principal investigator
University of Maryland
Denis Antoine, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Methadone (100% dose) and Methadone (50% dose) in people with Opioid Use Disorder and Chronic Pain, run by University of Maryland, Baltimore 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 8 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: looking for participants now, as of the sponsor's last update on 3 Feb 2026. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelly E Dunn, PhD, M.B.A. (802-922-1682, kelly.dunn@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in worst pain rating- past 24 hour as assessed by the Brief Pain Inventory scale (time frame: Week 1 up to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05459402, which also lists 1 linked publication.
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 3 Feb 2026.