Opioid Use Disorder (OUD)Phase 1NCT06877858
MethaLoad Dose-Finding Study
A Phase 1 study testing Methadone hydrochloride in people with Opioid Use Disorder (OUD), run by Ashish P Thakrar, MD MS at 1 site in United States.
Trial summary
Methadone is an effective treatment for opioid use disorder (OUD), but starting it has become harder now that most people with OUD use fentanyl. Methadone is usually started at a low dose and increased slowly over several weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use Disorder (OUD)
- What is being tested?
- Methadone hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2025to Jan 2028
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male, female, transgender, or non-binary, aged 18 years or older
- DSM-5 criteria for opioid use disorder, moderate-severe
- Fentanyl positive urine drug test
- Able to provide a dated \& written informed consent in English prior to the conduct of any study related procedures
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to take oral medication and be willing to adhere to the dosage regimen
- Interest in starting methadone treatment for opioid use disorder at a partner location
- Reliable access to a working phone
Who cannot join
- Hypersensitivity or allergy to methadone that is previously documented
- Pregnancy or actively lactating (with urine pregnancy test performed on screening and repeated on admission to the unit prior to randomization)
- Taking medications for opioid use disorder, per self-report or per urine drug testing detection of buprenorphine or methadone
- At risk of benzodiazepine or alcohol withdrawal as defined by: prior benzodiazepine or alcohol withdrawal in the past 3 months, current daily use of benzodiazepines or alcohol, or DSM-5 criteria for hypnotic-sedative or alcohol use disorder
- At risk of severe medetomidine withdrawal based on: serum or urine testing for medetomidine (if available), prior withdrawal syndrome requiring intensive care unit admission within past 6 months, and/or severe nausea/vomiting during first 4 hours of withdrawal, at the discretion of the study physicians
- At risk for methadone-induced QT-prolongation: prolonged QTc on screening or admission EKG (greater than 450ms in men, greater than 460ms in women), history of QT prolongation, previously documented long QT syndrome, history of ventricular arrhythmia (e.g., torsades de pointes), history of cardiac hypertrophy, history of cardiac conduction abnormalities, taking medications that affect cardiac conduction (at study physician discretion; including but not limited to: amiodarone, flecainide, sotalol, azithromycin, ciprofloxacin, levofloxacin, citalopram, escitalopram, hydroxychloroquine, chlorpromazine, haloperidol, donepezil, ibogaine, cilostazol), serum potassium concentration less than 3.5 mg/dL, or serum magnesium concentration less than 1.7 mg/dL.
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- Significant hepatic dysfunction, defined as: AST and/or ALT 3x upper limit of normal, or total bilirubin 1.5x upper limit of normal
- Significant renal dysfunction, defined as: eGFR less than or equal to 60 mL/min
- Chronic hypotension (<90/50 mmHg) or episodic symptomatic hypotension, defined as a history of active or recurrent orthostatic hypotension or syncope
- Significant pulmonary disease, defined as: baseline SpO2 <95% on screening or admission, requiring oxygen at home (chronically or at bedtime), or COPD with modified MRC Dyspnea Scale greater than 2 ("I stop for breath after walking about one city block")
- Suspected gastrointestinal obstruction, per medical history
- Active, chronic use of the CYP3A4-inducers or -inhibitors rifampin, phenytoin, St John's wort, phenobarbital, carbamazepine, voriconazole, efavirenz, nelfinavir, nevirapine, ritonavir, and lopinavir/ritonavir, abacavir, or amprenavir
- Pending legal action that could prohibit participation and/or compliance in study procedures
- Presence of any other psychiatric and/or medical disorder that, in the opinion of the PI, will interfere with completion of the study or place the patient at heightened risk through participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Kyle Kampman, MD contact
United States1 site, 1 recruiting
- Recruiting
Penn Center for Studies of Addiction (CSA)
Philadelphia, Pennsylvania, 19104
Megan Ivey, 215-746-0222, Megan.Ivey@pennmedicine.upenn.edu
Ashish P Thakrar, MD, MS
About this study
Official title: A Dose-Finding Study of Methadone Loading Dose Initiation for Opioid Use Disorder With Fentanyl Use
Methadone is an effective treatment for opioid use disorder (OUD), but starting it has become harder now that most people with OUD use fentanyl. Methadone is usually started at a low dose and increased slowly over several weeks. For people who use fentanyl, these low early doses might not relieve withdrawal and cravings, and many people stop treatment before reaching a dose that works.
This study will test whether starting methadone with a higher first-day dose (a "loading dose") is safe and comfortable for people who use fentanyl. It will also help find the best loading dose to test in future, larger studies.
We will enroll 24 adults with OUD who use fentanyl. Participants will start methadone while staying on an inpatient research unit, where staff will monitor them closely. Each person will get either the usual starting dose or one of four loading doses, assigned by chance. Participants and the staff who rate their symptoms will not know which dose was given. As the study goes on, the research team will use safety results from earlier participants to decide which loading doses later participants receive.
- Conditions
- Opioid Use Disorder (OUD)
- Being tested
- Methadone hydrochloride
- Keywords
- methadone, fentanyl, opioid use disorder, opioid addiction, opiate addiction, OUD
- 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.
Methadone hydrochlorideDrug
Methadone loading dose initiation (vs. standard initiation in the TAU arm)
| Study group | Role | What they receive |
|---|---|---|
| Treatment as usual (TAU) | Active comparator | Day 1: 40mg oral methadone Day 2: 40mg oral methadone Receives: Drug: Methadone hydrochloride |
| Loading Dose | Experimental | Day 1: loading dose (60mg, 80mg, 100mg, or 120mg oral methadone) Day 2: 50% of the loading dose (30mg, 40mg, 50, or 60mg oral methadone) Receives: Drug: Methadone hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) rate
The primary objective of the study is to identify a methadone loading dose approach appropriate for future study as an alternative initiation strategy for individuals with OUD using fentanyl or other high-potency synthetic opioids.
The loading dose appropriate for future study will be identified as the highest loading dose with a dose-limiting toxicity (DLT) rate less than 10%. DLT definition: the proportion of individuals in each loading dose arm who meet any one of four safety outcomes within 24 hours of methadone loading dose administration: (1) Richmond Agitation-Sedation Scale (RASS) less than -1, (2) respiratory rate (RR) less than 8 breaths per minute, (3) peripheral oxygen saturation (SpO2) less than 92%, or (4) corrected QT interval (QTc) greater than 500ms.
Measured: 24 hours
Secondary outcomes (3)
Opioid withdrawal severity
Peak and time-weighted mean subjective opioid withdrawal (using the Subjective Opioid Withdrawal Scale, SOWS) and the Clinical Opiate Withdrawal Scale (COWS) over 24 hours after initial methadone dose
Measured: 24 hours
Opioid craving
Peak and time-weighted mean opioid craving, using a visual analogue scale (VAS) assessment (1-100) over 24 hours after initial methadone dose
Measured: 24 hours after initial methadone dose
Peak plasma methadone concentration
Peak plasma methadone concentration after initial loading dose (Day 1) and after first maintenance dose (Day 2)
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2025
- Study start25 Sep 2025
- Primary completion31 Dec 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use Disorder (OUD)Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Bayesian Optimal Interval Design (BOIN) for dose-finding studies
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ashish P Thakrar, MD MS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ashish P Thakrar, MD MS, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06877858
- Sponsor's protocol ID
- 857972
- Status last verified
- Oct 2025
- First submitted
- 10 Mar 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-Finding Study of Methadone Loading Dose Initiation for Opioid Use Disorder With Fentanyl Use
- ClinicalTrials.gov ID
- NCT06877858
- Acronym / sponsor ID
- 857972
- Conditions
- Opioid Use Disorder (OUD)
- Keywords
- methadone, fentanyl, opioid use disorder, opioid addiction, opiate addiction, OUD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ashish P Thakrar, MD MSUniversity, hospital or other
- Study start
- 25 Sep 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 14 Mar 2025 (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.
Methadone is an effective treatment for opioid use disorder (OUD), but starting it has become harder now that most people with OUD use fentanyl. Methadone is usually started at a low dose and increased slowly over several weeks. For people who use fentanyl, these low early doses might not relieve withdrawal and cravings, and many people stop treatment before reaching a dose that works.
This study will test whether starting methadone with a higher first-day dose (a "loading dose") is safe and comfortable for people who use fentanyl. It will also help find the best loading dose to test in future, larger studies.
We will enroll 24 adults with OUD who use fentanyl. Participants will start methadone while staying on an inpatient research unit, where staff will monitor them closely. Each person will get either the usual starting dose or one of four loading doses, assigned by chance. Participants and the staff who rate their symptoms will not know which dose was given. As the study goes on, the research team will use safety results from earlier participants to decide which loading doses later participants receive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Bayesian Optimal Interval Design (BOIN) for dose-finding studies
| Arm | Type | Receives |
|---|---|---|
| Treatment as usual (TAU) | Active comparator | Drug: Methadone hydrochlorideDay 1: 40mg oral methadone Day 2: 40mg oral methadone |
| Loading Dose | Experimental | Drug: Methadone hydrochlorideDay 1: loading dose (60mg, 80mg, 100mg, or 120mg oral methadone) Day 2: 50% of the loading dose (30mg, 40mg, 50, or 60mg oral methadone) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male, female, transgender, or non-binary, aged 18 years or older
- DSM-5 criteria for opioid use disorder, moderate-severe
- Fentanyl positive urine drug test
- Able to provide a dated \& written informed consent in English prior to the conduct of any study related procedures
- Stated willingness to comply with all study procedures and availability for the duration of the study
Key exclusion criteria (14 listed)
- Hypersensitivity or allergy to methadone that is previously documented
- Pregnancy or actively lactating (with urine pregnancy test performed on screening and repeated on admission to the unit prior to randomization)
- Taking medications for opioid use disorder, per self-report or per urine drug testing detection of buprenorphine or methadone
- At risk of benzodiazepine or alcohol withdrawal as defined by: prior benzodiazepine or alcohol withdrawal in the past 3 months, current daily use of benzodiazepines or alcohol, or DSM-5 criteria for hypnotic-sedative or alcohol use disorder
- At risk of severe medetomidine withdrawal based on: serum or urine testing for medetomidine (if available), prior withdrawal syndrome requiring intensive care unit admission within past 6 months, and/or severe nausea/vomiting during first 4 hours of withdrawal, at the discretion of the study physicians
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 hydrochlorideMethadone loading dose initiation (vs. standard initiation in the TAU arm) | Drug | Loading Dose, Treatment as usual (TAU) |
Primary outcome
Dose-limiting toxicity (DLT) rate
Time frame: 24 hours
The primary objective of the study is to identify a methadone loading dose approach appropriate for future study as an alternative initiation strategy for individuals with OUD using fentanyl or other high-potency synthetic opioids. The loading dose appropriate for future study will be identified as the highest loading dose with a dose-limiting toxicity (DLT) rate less than 10%. DLT definition: the proportion of individuals in each loading dose arm who meet any one of four safety outcomes within 24 hours of methadone loading dose administration: (1) Richmond Agitation-Sedation Scale (RASS) less than -1, (2) respiratory rate (RR) less than 8 breaths per minute, (3) peripheral oxygen saturation (SpO2) less than 92%, or (4) corrected QT interval (QTc) greater than 500ms.
3 secondary outcomes
Opioid withdrawal severity
Time frame: 24 hours
Opioid craving
Time frame: 24 hours after initial methadone dose
Peak plasma methadone concentration
Time frame: 48 hours
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 19 Oct 2026.
- Individual participant dataSharing planned: Yes
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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.
Kyle Kampman, MD contact
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 Methadone hydrochloride in people with Opioid Use Disorder (OUD), run by Ashish P Thakrar, MD MS 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 8 inclusion and 14 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 19 Oct 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 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?
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 Ashish P Thakrar, MD, MS ((215) 662-2250, apthakrar@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) rate (time frame: 24 hours). 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 19 Oct 2026.