Obesity & OverweightPhase 4OFF-RAMPNCT07832084
Comparing Different Medication Regimens to Maintaining Weight Loss Among Adults With Obesity Using GLP-1s
A Phase 4 study testing GLP-1 dose reduction, non-GLP weight loss medication and Maintenance of GLP-1 dose in people with Obesity & Overweight and Cardiometabolic Health Indicators, run by Jing Luo at 1 site in United States.
Trial summary
The purpose of this research is to compare weight loss among 3 groups: 1. people who stay on a GLP-1 drug at full strength (Group 1) 2. people who have their dose tapered to every other week, meaning slowly decreasing the dose and frequency of the full prescription you are currently taking (Group 2) 3. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity & Overweight, Cardiometabolic Health Indicators
- What is being tested?
- GLP-1 dose reduction, non-GLP weight loss medication and Maintenance of GLP-1 dose
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2026to 30 Sep 2028
- Phase
- Phase 4
- 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
Participant Inclusion Criteria:
- Aged 18 years or older.
- Able to provide informed consent.
- Pre-treatment diagnosis of obesity (BMI≥30kg/m2).
- On a high potency GLP-1 based therapy (defined as semaglutide ≥1.7 mg or tirzepatide≥10mg).
- Has achieved, or are close to achieving, a "target body weight." Target body weight will be defined by each individual patient through self-report or their treating clinician but should generally be at least 5% below their weight prior to first starting GLP-1 based therapy.
- Has been on an incretin-based weight loss therapy for at least 6 months.
Participant Exclusion Criteria:
- Diagnosis of type 2 diabetes or pre-existing cardiovascular disease.
- Pregnancy or nursing or are seeking to become pregnant in the next year.
- Have had bariatric surgery.
- Unwilling to reduce the dose of their GLP-1 medication for weight loss, or who are unwilling to switch to another non-GLP-1based weight loss medication.
- Contraindications to phentermine: pre-existing cardiac arrhythmias, primary pulmonary hypertension, serious cardiac valvular disease, CAD, CVA, CHF, uncontrolled hypertension.
- Contraindications to bupropion/naltrexone: chronic opioid use, seizure disorders, use of other bupropion containing products, uncontrolled hypertension, monoamine oxidase inhibitors.
- Hyperthyroidism.
- Glaucoma, or at risk for glaucoma.
- History of substance use disorder.
- History of suicidal ideation.
- Concomitant monoamine oxidase inhibitors within 14 days.
- Use of lithium.
- Use of metformin.
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
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232
Jing Luo, MD, 412-383-3559, luoj@pitt.edu
About this study
Official title: OFF-RAMP Feasibility: a Pilot Trial Comparing Different Off-ramping Strategies for Maintaining Weight Loss Among Adults Using Incretin Based Therapies for Obesity
The purpose of this research is to compare weight loss among 3 groups:
- people who stay on a GLP-1 drug at full strength (Group 1)
- people who have their dose tapered to every other week, meaning slowly decreasing the dose and frequency of the full prescription you are currently taking (Group 2)
- people who go off their GLP-1 and instead take an alternative weight loss drug or combination of drugs called phentermine \& topiramate. These are not GLP-1 medications. (Group 3)
Read more
The investigators want to see if the second and third options are effective at weight loss maintenance.
This study will include a total of 60 participants. Participants will be randomly assigned to one of the three study groups.
The goals of this current study are to:
- determine the acceptability of these proposed treatment strategies,
- collect data about how people's weight changes early on and throughout the study and how well people tolerate the medications.
- determine whether it is feasible to recruit for a larger, follow-up study.
There are 3 on-site visits: at the start, and then 6 and 12 months. The study team will do monthly phone calls in between those visits. At the on-site visits the study team will do various physical measures and collect blood for lab testing and provide participants with counseling to help with weight loss.
The study team will instruct participants in a home-based resistance exercise regimen to help maintain muscle mass. This will include exercises such as: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, and bicep curls two to three times a week. If these exercises are deemed too easy, participants may choose to do regular pushups, planks, lunges and/or add a resistance band.
- Being tested
- GLP-1 dose reduction, non-GLP weight loss medication, Maintenance of GLP-1 dose, Resistance exercise regimen, Lifestyle/nutrition counseling
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1 dose reductionDrug
Participants in this intervention arm will receive a reduced GLP-1 dose compared to usual care.
non-GLP weight loss medicationDrug
Participants in this intervention arm will be switched to a non-GLP weight loss medication.
Maintenance of GLP-1 doseDrug
Participants in this arm will maintain their high-potency GLP-1 dosage.
Resistance exercise regimenBehavioural
All participants will be recommended to do a "low touch" home-based resistance exercise regimen. These strength exercises will include: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, bicep curls two to three times a week. If too easy for a particular subject, the study may recommend regular push ups, planks, lunges and/or add a resistance band.
Lifestyle/nutrition counselingBehavioural
Participants will be provided with guideline concordant weight loss maintenance education and counseling (i.e., calorie restriction, amount and intensity of physical activity, self-monitoring of weight, and measuring portion sizes).
| Study group | Role | What they receive |
|---|---|---|
| Usual care | Active comparator | Maintenance of high-potency GLP-1 based therapy. Participants will continue their dose at enrollment for the entire duration of study follow-up. This is the current standard of care when the medication is covered and available. Receives: Drug: Maintenance of GLP-1 dose; Behavioral: Resistance exercise regimen; Behavioral: Lifestyle/nutrition counseling |
| Low dose, alternate frequency | Experimental | GLP-1 dose reduction to lower-dose, alternate frequency. Participants on semaglutide at enrollment will gradually reduce their dose from 2.4mg to 1.7mg to 1.0mg to 0.5mg once a week to 0.5mg every other week. Participants on tirzepatide at baseline will gradually reduce their dose from 15mg to 12.5mg to 10mg to 7.5mg to 5mg once a week to 5mg every other week. Dose reductions are scheduled every 4 weeks. Receives: Drug: GLP-1 dose reduction; Behavioral: Resistance exercise regimen; Behavioral: Lifestyle/nutrition counseling |
| Non-incretin based therapy | Experimental | After gradually reducing GLP-1 therapy, participants will start phentermine with topiramate. Participants will reduce their semaglutide or tirzepatide dosage following the schedule of the "low dose, alternate frequency" arm until either semaglutide is 0.5mg once a week or tirzepatide is 5mg once a week. Participants will then start phentermine at 15mg once a day. Four weeks later, they will add topiramate at 25mg once a day. Four weeks later, they will increase the phentermine dose to 30mg once a day. Four weeks later, they will increase topiramate to 50mg once a day. Participants who cannot tolerate or have contraindications to phentermine will be offered bupropion + naltrexone. Dosages for bupropion would start at 75mg twice a day (maintenance dose 150mg twice a day). Dosages for naltrexone would start at 25mg per day. For subjects where a review by the PI or Co-I suggest a favorable benefit/risk profile, an option would be provided to increase naltrexone to 25mg twice per day. Receives: Drug: non-GLP weight loss medication; Behavioral: Resistance exercise regimen; Behavioral: Lifestyle/nutrition counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of recruitment and retention
The primary study endpoint is feasibility. This trial will be considered feasible if the study achieves:
- ≥60% consent to approach rate.
- ≥80% enrolled to consent rate.
- A total of at least 60 participants (20 per study arm).
- ≥80% protocol completion rate among enrolled participants at 6 months.
- ≥70% protocol completion rate among enrolled participants at 12 months.
Measured: Completion of participation, up to 12 months.
Secondary outcomes (1)
Acceptability of lower-dose, alternate frequency dosing or switching to non-incretin based weight loss therapy
Acceptability of the individual comparators will be based on participant responses to a survey questionnaire developed for this study. The proposed comparators will be considered acceptable if at the 6-month study visit:
- ≥70% of patients would recomend the intervention to other patients using incretin based therapies for weight loss, OR
- ≥70% of patients agree or strongly agree that the randomly assigned intervention has "helped me maintain me weight loss or level of function".
Measured: 6-month study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2026
- Study startDec 2026 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity & OverweightStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jing Luo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jing Luo, University of Pittsburgh
- Investigators
- Jing Luo, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07832084
- Sponsor's protocol ID
- STUDY26060140
- Other IDs
- 1R01DK148666
- Acronym
- OFF-RAMP
- Status last verified
- Sep 2026
- First submitted
- 15 Sep 2026
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant level data generated from the PI's institution (UPMC) will be shared to eligible individuals by request in writing to the PI and through deposit in Zenodo (see below). Data sharing at the de-identified individual level will be sufficient to replicate the study results. These data made available must be under terms and conditions consistent with the informed consent provided by individual participants, and as approved by the awardees' Institutional Review Board (IRB) and any local, state and Federal laws and regulations
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OFF-RAMP Feasibility: a Pilot Trial Comparing Different Off-ramping Strategies for Maintaining Weight Loss Among Adults Using Incretin Based Therapies for Obesity
- ClinicalTrials.gov ID
- NCT07832084
- Acronym / sponsor ID
- OFF-RAMP / STUDY26060140
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Jing LuoUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Dec 2026 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 21 Sep 2026 (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.
The purpose of this research is to compare weight loss among 3 groups:
- people who stay on a GLP-1 drug at full strength (Group 1)
- people who have their dose tapered to every other week, meaning slowly decreasing the dose and frequency of the full prescription you are currently taking (Group 2)
- people who go off their GLP-1 and instead take an alternative weight loss drug or combination of drugs called phentermine \& topiramate. These are not GLP-1 medications. (Group 3)
The investigators want to see if the second and third options are effective at weight loss maintenance.
This study will include a total of 60 participants. Participants will be randomly assigned to one of the three study groups.
The goals of this current study are to:
- determine the acceptability of these proposed treatment strategies,
- collect data about how people's weight changes early on and throughout the study and how well people tolerate the medications.
- determine whether it is feasible to recruit for a larger, follow-up study.
There are 3 on-site visits: at the start, and then 6 and 12 months. The study team will do monthly phone calls in between those visits. At the on-site visits the study team will do various physical measures and collect blood for lab testing and provide participants with counseling to help with weight loss.
The study team will instruct participants in a home-based resistance exercise regimen to help maintain muscle mass. This will include exercises such as: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, and bicep curls two to three times a week. If these exercises are deemed too easy, participants may choose to do regular pushups, planks, lunges and/or add a resistance band.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Usual care | Active comparator | Drug: Maintenance of GLP-1 dose, Behavioral: Resistance exercise regimen, Behavioral: Lifestyle/nutrition counselingMaintenance of high-potency GLP-1 based therapy. Participants will continue their dose at enrollment for the entire duration of study follow-up. This is the current standard of care when the medication is covered and available. |
| Low dose, alternate frequency | Experimental | Drug: GLP-1 dose reduction, Behavioral: Resistance exercise regimen, Behavioral: Lifestyle/nutrition counselingGLP-1 dose reduction to lower-dose, alternate frequency. Participants on semaglutide at enrollment will gradually reduce their dose from 2.4mg to 1.7mg to 1.0mg to 0.5mg once a week to 0.5mg every other week. Participants on tirzepatide at baseline will gradually reduce their dose from 15mg to 12.5mg to 10mg to 7.5mg to 5mg once a week to 5mg every other week. Dose reductions are scheduled every 4 weeks. |
| Non-incretin based therapy | Experimental | Drug: non-GLP weight loss medication, Behavioral: Resistance exercise regimen, Behavioral: Lifestyle/nutrition counselingAfter gradually reducing GLP-1 therapy, participants will start phentermine with topiramate. Participants will reduce their semaglutide or tirzepatide dosage following the schedule of the "low dose, alternate frequency" arm until either semaglutide is 0.5mg once a week or tirzepatide is 5mg once a week. Participants will then start phentermine at 15mg once a day. Four weeks later, they will add topiramate at 25mg once a day. Four weeks later, they will increase the phentermine dose to 30mg once a day. Four weeks later, they will increase topiramate to 50mg once a day. Participants who cannot tolerate or have contraindications to phentermine will be offered bupropion + naltrexone. Dosages for bupropion would start at 75mg twice a day (maintenance dose 150mg twice a day). Dosages for naltrexone would start at 25mg per day. For subjects where a review by the PI or Co-I suggest a favorable benefit/risk profile, an option would be provided to increase naltrexone to 25mg twice per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| GLP-1 dose reductionParticipants in this intervention arm will receive a reduced GLP-1 dose compared to usual care. | Drug | Low dose, alternate frequency |
| non-GLP weight loss medicationParticipants in this intervention arm will be switched to a non-GLP weight loss medication. | Drug | Non-incretin based therapy |
| Maintenance of GLP-1 doseParticipants in this arm will maintain their high-potency GLP-1 dosage. | Drug | Usual care |
| Resistance exercise regimenAll participants will be recommended to do a "low touch" home-based resistance exercise regimen. These strength exercises will include: sit-to-stand, mini-squats, calf raises, leg extension, wall press-up, bicep curls two to three times a week. If too easy for a particular subject, the study may recommend regular push ups, planks, lunges and/or add a resistance band. | Behavioural | Low dose, alternate frequency, Non-incretin based therapy, Usual care |
| Lifestyle/nutrition counselingParticipants will be provided with guideline concordant weight loss maintenance education and counseling (i.e., calorie restriction, amount and intensity of physical activity, self-monitoring of weight, and measuring portion sizes). | Behavioural | Low dose, alternate frequency, Non-incretin based therapy, Usual care |
Primary outcome
Feasibility of recruitment and retention
Time frame: Completion of participation, up to 12 months.
The primary study endpoint is feasibility. This trial will be considered feasible if the study achieves: * ≥60% consent to approach rate. * ≥80% enrolled to consent rate. * A total of at least 60 participants (20 per study arm). * ≥80% protocol completion rate among enrolled participants at 6 months. * ≥70% protocol completion rate among enrolled participants at 12 months.
1 secondary outcome
Acceptability of lower-dose, alternate frequency dosing or switching to non-incretin based weight loss therapy
Time frame: 6-month study visit
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 Nov 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant level data generated from the PI's institution (UPMC) will be shared to eligible individuals by request in writing to the PI and through deposit in Zenodo (see below). Data sharing at the de-identified individual level will be sufficient to replicate the study results. These data made available must be under terms and conditions consistent with the informed consent provided by individual participants, and as approved by the awardees' Institutional Review Board (IRB) and any local, state and Federal laws and regulations
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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.
Jing Luo, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing GLP-1 dose reduction, non-GLP weight loss medication and Maintenance of GLP-1 dose in people with Obesity & Overweight and Cardiometabolic Health Indicators, run by Jing Luo 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?
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: opening soon, as of the sponsor's last update on 3 Nov 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Jing Luo, MD (412-383-3559, luoj@pitt.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of recruitment and retention (time frame: Completion of participation, up to 12 months.). 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 3 Nov 2026.