ObesityPhase 3NCT05157698
Pharmacological and Behavioral Treatment After Bariatric Surgery
A Phase 3 study testing Naltrexone and Bupropion Combination and Behavioral Weight Loss in people with Obesity, run by Yale University at 1 site in United States.
Trial summary
This study will compare the effectiveness of behavioral and pharmacologic treatment, alone and combined, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning following metabolic and bariatric surgery. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Obesity
- What is being tested?
- Naltrexone and Bupropion Combination and Behavioral Weight Loss
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2022to 25 May 2026
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study (up to 18 months: 6-month treatment plus 12-month follow up)
- Have a BMI ≥30 (or BMI ≥27 with a medical comorbidity) and BMI ≤50 kg/m2
- Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
- Suboptimal weight outcomes after MBS
- Be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators (physical examination, laboratory studies).
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- Have had a physical in the past year
- Read, comprehend, and write English at a sufficient level to complete study-related materials.
- For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
Who cannot join
- Has a predisposition to seizures (e.g., subject with a history or evidence of seizure disorder, febrile seizures during childhood, brain tumor, cerebrovascular disease, or significant head trauma; has a family history of idiopathic seizure disorder or is currently being treated with medications or treatment regimens that lower seizure threshold).
- Has a history of anorexia nervosa or history of bulimia nervosa.
- Is currently taking a medication that is a contraindication to NB medication (e.g., MAOI, opiates).
- Is currently using other medications for weight loss.
- Has a history of allergy or sensitivity to bupropion or naltrexone.
- Has a co-existing psychiatric condition that requires hospitalization or more intensive treatment (such as bipolar mood disorders, psychotic illnesses, or severe depression)
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- Has untreated hypertension with a seated systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg, or heart rate > 100 beats/minute.
- Has a history of congenital heart disease, cardiovascular disease, cardiac arrhythmias requiring medication, or a history of cerebrovascular pathology including stroke.
- Has current uncontrolled hypertension.
- Has current uncontrolled Type I or Type 2 diabetes mellitus.
- Has untreated hypothyroidism with a TSH > 1.5 times the upper limit of normal for the test laboratory with repeat value that also exceeds this limit.
- Has gallbladder disease.
- Has a history of severe renal, hepatic, neurological, chronic pulmonary disease, or any other unstable medical disorder.
- Has a recent history of drug or alcohol dependence.
- Is currently in active effective treatment for eating or weight loss such as behavioral weight loss of FDA-approved weight loss medications.
- Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug or device.
- Is breast-feeding or is pregnant or is not using a reliable form of birth control.
- Reports active suicidal or homicidal ideation.
- Has poor eye health
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale School of Medicine
New Haven, Connecticut, 06519
About this study
Official title: Behavioral and Pharmacological Treatments to Enhance Weight Outcomes After Metabolic and Bariatric Surgery
This study will compare the effectiveness of behavioral and pharmacologic treatment, alone and combined, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning following metabolic and bariatric surgery.
Read the detailed description
Metabolic and bariatric surgery is currently the most effective treatment for severe obesity; however, a substantial proportion of patients attain suboptimal weight losses and continue to struggle with obesity, weight regain, and related medical comorbidities after surgery. Thus, this study aims to perform a randomized double-blind placebo-controlled study to test the effectiveness of a rigorous manualized behavioral weight loss treatment and a FDA-approved weight loss agent (naltrexone+bupropion), alone and in combination, for improving weight loss, cardiovascular risk factors, and psychosocial functioning after metabolic and bariatric surgery. This study will produce important new clinical findings regarding the utility and effectiveness of pharmacotherapy and behavioral weight loss for a rapidly growing obesity subgroup and will inform care models for managing chronic and refractory obesity to enhance outcomes after metabolic and bariatric surgery.
- Conditions
- Obesity
- Being tested
- Naltrexone and Bupropion Combination, Behavioral Weight Loss, Placebo
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naltrexone and Bupropion CombinationDrug
Participants in this intervention will take active naltrexone and bupropion pills.
Behavioral Weight LossBehavioural
Participants in this intervention will receive behavioral weight loss treatment.
PlaceboOther
Participants in this intervention will take inactive (placebo) pills.
| Study group | Role | What they receive |
|---|---|---|
| BWL + NB medication | Experimental | Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form. Receives: Drug: Naltrexone and Bupropion Combination; Behavioral: Behavioral Weight Loss |
| BWL + Placebo | Experimental | Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and placebo. Placebo will be inactive and taken daily in pill form. Receives: Behavioral: Behavioral Weight Loss; Other: Placebo |
| NB medication | Experimental | Participants randomly assigned to this arm will receive 6 months of NB medication taken daily in pill form. Receives: Drug: Naltrexone and Bupropion Combination |
| Placebo | Placebo comparator | Participants randomly assigned to this arm will receive 6 months of placebo. Placebo will be inactive and taken daily in pill form. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Body Mass Index (BMI)
BMI is calculated using measured height and weight
Measured: Baseline to after the 6-month treatment
Change in Body Mass Index (BMI)
BMI is calculated using measured height and weight
Measured: From post-treatment (6-months) to the 12-month follow-up
Secondary outcomes (14)
Change in Total cholesterol
Total cholesterol will be measured by bloodwork.
Measured: From baseline at study enrollment to after the 6-month treatment
Change in Total cholesterol
Total cholesterol will be measured by bloodwork.
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in HbA1C
HbA1C will be measured by bloodwork.
HbA1C
Measured: From baseline at study enrollment to after the 6-month treatment
Change in HbA1C
HbA1C will be measured by bloodwork.
HbA1C
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in Glucose
Glucose will be measured by bloodwork.
Measured: From baseline at study enrollment to after the 6-month treatment
Change in Glucose
Glucose will be measured by bloodwork.
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in Loss-of-Control Eating Frequency
Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes .during the past 28 days assessed using the Eating Disorder Examination interview
Measured: From baseline interview at study enrollment to after the 6-month treatment
Change in Loss-of-Control Eating Frequency
Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes during the past 28 days assessed using the Eating Disorder Examination interview.
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in Eating Disorder Psychopathology
Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology).
Measured: From baseline interview at study enrollment to after the 6-month treatment
Change in Eating Disorder Psychopathology
Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology).
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in Food Craving
Food craving is a continuous variable of food craving as assessed by the Food Craving Inventory. Scores range from 0-5 (0=no food craving; 5=greatest food craving).
Measured: From baseline interview at study enrollment to after the 6-month treatment
Change in Food Craving
Food craving is a continuous variable of food craving as assessed by the Food Craving Inventory. Scores range from 0-5 (0=no food craving; 5=greatest food craving).
Measured: From post-treatment (6-months) to the 12-month follow-up
Change in Depressive Symptoms
Depressive Symptoms [ Time Frame: From baseline interview at study enrollment to after the 6-month treatment ] Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).
Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).
Measured: From baseline interview at study enrollment to after the 6-month treatment
Change in Depressive Symptoms
Depressive Symptoms [ Time Frame: From baseline interview at study enrollment to after the 6-month treatment ] Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).
Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).
Measured: From post-treatment (6-months) to the 12-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2021
- Study start13 Jan 2022
- Primary completion25 May 2026
- Study completion25 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Valentina Ivezaj, Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05157698
- Sponsor's protocol ID
- 2000029934
- Other IDs
- 1R01DK125650-01A1
- Status last verified
- Sep 2026
- First submitted
- 22 Nov 2021
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Behavioral and Pharmacological Treatments to Enhance Weight Outcomes After Metabolic and Bariatric Surgery
- ClinicalTrials.gov ID
- NCT05157698
- Acronym / sponsor ID
- 2000029934
- Conditions
- Obesity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 13 Jan 2022 (actual)
- Primary completion
- 25 May 2026 (actual)
- Study completion
- 25 May 2026 (actual)
- First posted
- 15 Dec 2021 (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 compare the effectiveness of behavioral and pharmacologic treatment, alone and combined, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning following metabolic and bariatric surgery.
Detailed description
Metabolic and bariatric surgery is currently the most effective treatment for severe obesity; however, a substantial proportion of patients attain suboptimal weight losses and continue to struggle with obesity, weight regain, and related medical comorbidities after surgery. Thus, this study aims to perform a randomized double-blind placebo-controlled study to test the effectiveness of a rigorous manualized behavioral weight loss treatment and a FDA-approved weight loss agent (naltrexone+bupropion), alone and in combination, for improving weight loss, cardiovascular risk factors, and psychosocial functioning after metabolic and bariatric surgery. This study will produce important new clinical findings regarding the utility and effectiveness of pharmacotherapy and behavioral weight loss for a rapidly growing obesity subgroup and will inform care models for managing chronic and refractory obesity to enhance outcomes after metabolic and bariatric surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BWL + NB medication | Experimental | Drug: Naltrexone and Bupropion Combination, Behavioral: Behavioral Weight LossParticipants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form. |
| BWL + Placebo | Experimental | Behavioral: Behavioral Weight Loss, Other: PlaceboParticipants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and placebo. Placebo will be inactive and taken daily in pill form. |
| NB medication | Experimental | Drug: Naltrexone and Bupropion CombinationParticipants randomly assigned to this arm will receive 6 months of NB medication taken daily in pill form. |
| Placebo | Placebo comparator | Other: PlaceboParticipants randomly assigned to this arm will receive 6 months of placebo. Placebo will be inactive and taken daily in pill form. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study (up to 18 months: 6-month treatment plus 12-month follow up)
- Have a BMI ≥30 (or BMI ≥27 with a medical comorbidity) and BMI ≤50 kg/m2
- Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
- Suboptimal weight outcomes after MBS
Key exclusion criteria (19 listed)
- Has a predisposition to seizures (e.g., subject with a history or evidence of seizure disorder, febrile seizures during childhood, brain tumor, cerebrovascular disease, or significant head trauma; has a family history of idiopathic seizure disorder or is currently being treated with medications or treatment regimens that lower seizure threshold).
- Has a history of anorexia nervosa or history of bulimia nervosa.
- Is currently taking a medication that is a contraindication to NB medication (e.g., MAOI, opiates).
- Is currently using other medications for weight loss.
- Has a history of allergy or sensitivity to bupropion or naltrexone.
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 |
|---|---|---|
| Naltrexone and Bupropion CombinationParticipants in this intervention will take active naltrexone and bupropion pills. | Drug | BWL + NB medication, NB medication |
| Behavioral Weight LossParticipants in this intervention will receive behavioral weight loss treatment. | Behavioural | BWL + NB medication, BWL + Placebo |
| PlaceboParticipants in this intervention will take inactive (placebo) pills. | Other | BWL + Placebo, Placebo |
Primary outcome
Change in Body Mass Index (BMI)
Time frame: Baseline to after the 6-month treatment
BMI is calculated using measured height and weight
Change in Body Mass Index (BMI)
Time frame: From post-treatment (6-months) to the 12-month follow-up
BMI is calculated using measured height and weight
14 secondary outcomes
Change in Total cholesterol
Time frame: From baseline at study enrollment to after the 6-month treatment
Change in Total cholesterol
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in HbA1C
Time frame: From baseline at study enrollment to after the 6-month treatment
Change in HbA1C
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in Glucose
Time frame: From baseline at study enrollment to after the 6-month treatment
Change in Glucose
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in Loss-of-Control Eating Frequency
Time frame: From baseline interview at study enrollment to after the 6-month treatment
Change in Loss-of-Control Eating Frequency
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in Eating Disorder Psychopathology
Time frame: From baseline interview at study enrollment to after the 6-month treatment
Change in Eating Disorder Psychopathology
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in Food Craving
Time frame: From baseline interview at study enrollment to after the 6-month treatment
Change in Food Craving
Time frame: From post-treatment (6-months) to the 12-month follow-up
Change in Depressive Symptoms
Time frame: From baseline interview at study enrollment to after the 6-month treatment
Change in Depressive Symptoms
Time frame: From post-treatment (6-months) to the 12-month follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- 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.
Valentina Ivezaj, Ph.D. principal investigator
Yale University
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 Naltrexone and Bupropion Combination and Behavioral Weight Loss in people with Obesity, run by Yale University 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 10 inclusion and 19 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: finished, as of the sponsor's last update on 21 Sep 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. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Body Mass Index (BMI) (time frame: Baseline to after the 6-month treatment). The study lists 2 primary outcomes in all. 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 21 Sep 2026.