Opioid-Related DisordersPhase 3pRESTONCT03948464
Slow-Release Oral Morphine for the Treatment of Opioid Use Disorder
A Phase 3 study testing Slow release oral morphine (SROM) and Methadone in people with Opioid-Related Disorders and Opiate Substitution Treatment, run by M. Eugenia Socias at 1 site in Canada.
Trial summary
This is a non-inferiority randomized clinical trial that will compare slow release oral morphine vs methadone as a second line oral treatment for opioid use disorder. Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Opioid-Related Disorders, Opiate Substitution Treatment, Morphine
- What is being tested?
- Slow release oral morphine (SROM) and Methadone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteCanada
- Study dates
- 6 Dec 2019to 1 Jun 2020
- Phase
- Phase 3
- 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 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all the following criteria to be eligible for the study:
- Be between 19 and 65 years of age, inclusively;
- Be diagnosed with opioid use disorder requiring opioid agonist treatment (OAT), as per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria and the discretion of the study physician;
- Be interested in receiving OAT;
- Be willing and eligible to be randomized to slow release oral morphine (SROM) or methadone-based OAT as per British Columbia guidelines;
- If female:
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- Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and over 45 years of age); or (ii) documented surgical sterilization (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
- If of childbearing potential, be willing to use an acceptable method of contraception throughout the study and have a negative pregnancy test at screening;
- Be able to provide written informed consent;
- Be willing to comply with study procedures;
- Be able to communicate in English;
Who cannot join
- Participants will be excluded from the study if any of the following criteria are met:
- Any disabling, severe, or unstable medical or psychiatric condition that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent, as assessed by medical and psychiatric history, physical examination, vital signs, and/or laboratory tests. These may include but are not limited to: significant respiratory depression, severe respiratory compromise or obstructive disease, severe respiratory distress, acute or severe bronchial asthma, known or suspected paralytic ileus;
- Any severe or unstable co-morbid substance use disorder (e.g., delirium tremens, acute alcohol intoxication) that, in the opinion of the study physician, precludes safe participation in the study;
- Maintenance on buprenorphine at doses of ≥4 mg in the 5 days prior to screening and stable in the opinion of the study physician;
- Maintenance on methadone at doses of ≥60 mg in the 5 days prior to screening and stable in the opinion of the study physician;
- Maintenance on slow release oral morphine at doses of ≥250 mg in the 5 days prior to screening and stable in the opinion of the study physician;
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- Pregnant, breastfeeding, or planning to become pregnant during the study period;
- History of a serious adverse drug reaction, hypersensitivity reaction, or allergy to methadone or SROM;
- Use of an investigational drug in the 30 days prior to screening;
- Pending legal action or other reasons that might prevent completion of the study;
- Current or anticipated need for treatment with any medication that may interact with methadone or SROM (e.g., benzodiazepines, monoamine oxidase inhibitors [MAOIs] pRESTO Protocol Version 3.0, 08 October 2019 Page 21 of 66 used currently or within the past 14 days) and that, in the opinion of the study physician, would be deemed unsafe or could prevent study completion.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Repurposing Slow-Release Oral Morphine as a New Oral Alternative for the Treatment of Opioid Use Disorder
This is a non-inferiority randomized clinical trial that will compare slow release oral morphine vs methadone as a second line oral treatment for opioid use disorder.
Read the detailed description
Slow-release oral morphine (SROM) has emerged as a promising yet understudied form of oral treatment for opioid use disorder (OUD), with preliminary studies suggesting similar efficacy rates as methadone with respect to promoting abstinence, and with better improvements in a number of patient-reported outcomes, including tolerability, treatment satisfaction, mental symptoms, and craving. The proposed study is an open-label, non-inferiority, randomized controlled trial evaluating the relative effectiveness, safety and acceptability of SROM vs. methadone for the treatment of OUD in outpatient clinical settings. Participants will be randomized 1:1 to SROM or methadone for 24 weeks. Data linkages performed three years after randomization will evaluate long term health outcomes. This study aims to provide evidence to optimize care for individuals with OUD, and potentially increase access to additional form of evidence-based oral treatment.
- Being tested
- Slow release oral morphine (SROM), Methadone
- Keywords
- slow-release oral morphine, methadone, opioid use disorder, fentanyl
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Slow release oral morphine (SROM)Drug
Also called Kadian
Slow release oral morphine is an opioid agonist. Slow release oral morphine will be administered via daily witnessed ingestion at designated community pharmacies.
MethadoneDrug
Also called Methadose/ Metadol D/Compounded methadone
Methadone is an opioid agonist. Methadone will be administered via daily witnessed ingestion at designated community pharmacies.
| Study group | Role | What they receive |
|---|---|---|
| Slow release oral morphine (SROM) | Experimental | Daily witnessed ingestion of SROM (24-hour formulation) for 24 weeks as per provincial and national guidelines for opioid use disorder. Receives: Drug: Slow release oral morphine (SROM) |
| Methadone | Active comparator | Daily witnessed ingestion of methadone for 24 weeks as per provincial and national guidelines for opioid use disorder. Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid Use
This will be measured by the overall proportion of opioid-free urine drug screens during the 24 weeks of active treatment (excluding the assigned therapy and it's metabolites), with missing samples defined as being positive for opioids
Measured: 24 weeks
Secondary outcomes (9)
Treatment Retention
Treatment retention will be measured by the proportion of participants on the assigned opioid agonist treatment (OAT) at the end of the study, defined as having both a) an active prescription for the assigned OAT at week 24, and b) a positive urine drug screen result for the assigned OAT at week 24.
Measured: 24 weeks
Adverse Events Related to Study Medications
The safety of each study medication will be evaluated by monitoring and gathering information on adverse events (AE) and serious adverse events (SAE), including overdoses, from the time of treatment initiation until the Safety Follow-up Visit. AEs and SAEs will be summarized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class and Preferred Term, and the frequency and nature of AEs and SAEs will be compared across treatment arms.
Measured: 24 weeks
Number of Overdose Events
Non-fatal overdoses since the previous visit will be assessed at baseline and every 12 weeks during the 24-week active treatment period, through a combination of self-report and participant's medical record. Data on fatal overdoses will be captured using vital statistics, and supplemented with information from contacts.
Measured: 24 weeks
Treatment Satisfaction: Medication Satisfaction Questionnaire (MSQ)
Participant satisfaction with the assigned treatment will be assessed through administration of the Medication Satisfaction Questionnaire (MSQ) at weeks 4, 12 and 24 of the study. This single-item patient-completed questionnaire evaluates participant's satisfaction with treatment medication on a 7-point Likert scale ranging from "extremely dissatisfied" to "extremely satisfied."
Measured: 24 weeks
Psychological Functioning
Psychological functioning will be measured by the "PROMIS (Patient-Reported Outcomes Measurement Information System) Emotional Distress -Anxiety-Short Form" and the "PROMIS Emotional Distress-Depression-Short Form" measures for anxiety and depression. These instruments will be administered at baseline, as well as at weeks 4, 12 and 24. These measures sum the frequency with which a participant experiences symptoms of depression and anxiety.
Measured: 24 weeks
Changes in Drug-Related Problems
The Addiction Severity Index (ASI) Self-Report Form will be used to assess changes in drug-related problems between baseline and week 24. The ASI has 34 questions. The answer value of each question is divided by its maximum answer value and the total number of questions, and the individual results are then summed to create a composite value.
Measured: 24 weeks
Changes in Quality of Life: EQ-5D-5L
Changes in health-related quality of life (HRQoL) between baseline and the end of treatment will be measured by the EuroQol "EQ-5D-5L" tool. The EQ-5D-5L will be administered at baseline and every 4 weeks during the 24-week active treatment period. The EQ-5D-5L includes a 5-level descriptive system and a visual analogue scale.The descriptive system has five categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which will be rated on a scale of 1 to 5 with 1 being the least severe and 5 being the most severe. The visual analogue scale is a vertical scale from 0 to 100, with 0 labelled "the worst health you can imagine" and 100 labelled "the best health you can imagine."
Measured: 24 weeks
Opioid Craving
Opioid cravings over time will be measured using a 100 mm visual analog scale (VAS). The VAS will be administered at baseline, week 2, week 4, and every 4 weeks for the remainder of the 24-week active treatment period. The VAS is a horizontal scale with 11 lines labeled from left to right with the numbers "0" to "10", and word anchors at each end representing the extremes, where "0=no craving" and "100 mm=most intense craving".
Measured: 24 weeks
Other Substance Use
Use of other substances will be measured using the Timeline Follow-Back (TLFB) instrument, which will be administered at baseline and every study visit thereafter.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start6 Dec 2019
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Why it stopped: Study unable to proceed per protocol due to COVID-19 precautions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-Related DisordersStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- M. Eugenia Socias
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Vancouver Foundation, Mayne Pharma International Pty Ltd
- Responsible party
- Sponsor-investigator, M. Eugenia Socias, BC Centre on Substance Use
- Investigators
- M. Eugenia Socias, MD, MSc, Principal investigator, BC Centre on Substance Use
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03948464
- Sponsor's protocol ID
- BCCSU-002
- Acronym
- pRESTO
- Status last verified
- Jan 2022
- First submitted
- 7 May 2019
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing Slow-Release Oral Morphine as a New Oral Alternative for the Treatment of Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT03948464
- Acronym / sponsor ID
- pRESTO / BCCSU-002
- Keywords
- slow-release oral morphine, methadone, opioid use disorder, fentanyl
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study unable to proceed per protocol due to COVID-19 precautions
- Enrolment
- 27 participants (actual)
- Lead sponsor
- M. Eugenia SociasUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Vancouver Foundation, Mayne Pharma International Pty Ltd
- Study start
- 6 Dec 2019 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 14 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 a non-inferiority randomized clinical trial that will compare slow release oral morphine vs methadone as a second line oral treatment for opioid use disorder.
Detailed description
Slow-release oral morphine (SROM) has emerged as a promising yet understudied form of oral treatment for opioid use disorder (OUD), with preliminary studies suggesting similar efficacy rates as methadone with respect to promoting abstinence, and with better improvements in a number of patient-reported outcomes, including tolerability, treatment satisfaction, mental symptoms, and craving. The proposed study is an open-label, non-inferiority, randomized controlled trial evaluating the relative effectiveness, safety and acceptability of SROM vs. methadone for the treatment of OUD in outpatient clinical settings. Participants will be randomized 1:1 to SROM or methadone for 24 weeks. Data linkages performed three years after randomization will evaluate long term health outcomes. This study aims to provide evidence to optimize care for individuals with OUD, and potentially increase access to additional form of evidence-based oral treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 1:1 randomization
| Arm | Type | Receives |
|---|---|---|
| Slow release oral morphine (SROM) | Experimental | Drug: Slow release oral morphine (SROM)Daily witnessed ingestion of SROM (24-hour formulation) for 24 weeks as per provincial and national guidelines for opioid use disorder. |
| Methadone | Active comparator | Drug: MethadoneDaily witnessed ingestion of methadone for 24 weeks as per provincial and national guidelines for opioid use disorder. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be between 19 and 65 years of age, inclusively;
- Be diagnosed with opioid use disorder requiring opioid agonist treatment (OAT), as per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria and the discretion of the study physician;
- Be interested in receiving OAT;
- Be willing and eligible to be randomized to slow release oral morphine (SROM) or methadone-based OAT as per British Columbia guidelines;
- If female:
Key exclusion criteria (11 listed)
- Any disabling, severe, or unstable medical or psychiatric condition that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent, as assessed by medical and psychiatric history, physical examination, vital signs, and/or laboratory tests. These may include but are not limited to: significant respiratory depression, severe respiratory compromise or obstructive disease, severe respiratory distress, acute or severe bronchial asthma, known or suspected paralytic ileus;
- Any severe or unstable co-morbid substance use disorder (e.g., delirium tremens, acute alcohol intoxication) that, in the opinion of the study physician, precludes safe participation in the study;
- Maintenance on buprenorphine at doses of ≥4 mg in the 5 days prior to screening and stable in the opinion of the study physician;
- Maintenance on methadone at doses of ≥60 mg in the 5 days prior to screening and stable in the opinion of the study physician;
- Maintenance on slow release oral morphine at doses of ≥250 mg in the 5 days prior to screening and stable in the opinion of the study physician;
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 |
|---|---|---|
| Slow release oral morphine (SROM)Also: KadianSlow release oral morphine is an opioid agonist. Slow release oral morphine will be administered via daily witnessed ingestion at designated community pharmacies. | Drug | Slow release oral morphine (SROM) |
| MethadoneAlso: Methadose/ Metadol D/Compounded methadoneMethadone is an opioid agonist. Methadone will be administered via daily witnessed ingestion at designated community pharmacies. | Drug | Methadone |
Primary outcome
Opioid Use
Time frame: 24 weeks
This will be measured by the overall proportion of opioid-free urine drug screens during the 24 weeks of active treatment (excluding the assigned therapy and it's metabolites), with missing samples defined as being positive for opioids
9 secondary outcomes
Treatment Retention
Time frame: 24 weeks
Adverse Events Related to Study Medications
Time frame: 24 weeks
Number of Overdose Events
Time frame: 24 weeks
Treatment Satisfaction: Medication Satisfaction Questionnaire (MSQ)
Time frame: 24 weeks
Psychological Functioning
Time frame: 24 weeks
Changes in Drug-Related Problems
Time frame: 24 weeks
Changes in Quality of Life: EQ-5D-5L
Time frame: 24 weeks
Opioid Craving
Time frame: 24 weeks
Other Substance Use
Time frame: 24 weeks
Results and safety
The study was stopped early (reason given: Study unable to proceed per protocol due to COVID-19 precautions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 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.
M. Eugenia Socias, MD, MSc principal investigator
BC Centre on Substance Use
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Slow release oral morphine (SROM) and Methadone in people with Opioid-Related Disorders and Opiate Substitution Treatment, run by M. Eugenia Socias at 1 site in Canada.
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 11 inclusion and 11 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 Feb 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 Canada. 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 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?
The study was stopped early (reason given: Study unable to proceed per protocol due to COVID-19 precautions). 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?
Opioid Use (time frame: 24 weeks). 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 Feb 2022.