Individualized Pharmacological Approach to Obesity in Patients With Bipolar Disorder

NCT07213466 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 25-005856
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to identify the specific characteristics (phenotypes) that may be useful to help select the right medication for weight loss, and to study the effect of individualized guided medication in patients with bipolar disorder ages 18-65. The main questions it aims to answer are:

• Can the investigators compare the distribution of obesity characteristics (hungry brain, hungry gut, emotional hunger) between bipolar patients and non-bipolar participants (comparing from IRB #24-002375)?
• Can the investigators evaluate the feasibility of anti-obesity medication (AOM) in patients with bipolar disorder? Participation will last for about 20 weeks and includes 8 in-person study visits, up to 11 phone call visits, and 13 virtual group therapy sessions. The first visit lasts about 2 hours and includes going over the informed consent form, a diagnostic interview to confirm diagnosis, gathering vital signs, mood questionnaires, an ECG, a blood draw, and urine drug and pregnancy tests (if applicable). The second visit lasts about 6-7 hours and involves multiple procedures and completing questionnaires to determine which study drug would allow participants to lose weight most effectively. At the third visit, participants will be assigned to take one of three FDA approved medications for weight loss: Semaglutide (Wegovy®), Naltrexone/Bupropion (Contrave®), or Phentermine/Topiramate (Qsymia®). It is possible that participants could be assigned to a group that receives no study medication. All participants will be enrolled in a 12-week virtual group therapy program targeted for weight loss. On this third visit the investigators will also gather vital signs, and participants will give a sample of blood. After the third visit, participants will come in for study visits every 4 weeks for 20 weeks (5 visits) to assess medication adherence, vitals, and answer questions about mood and eating (participants will also give a sample of blood at the 8-week and 20-week visits). For participants assigned to a study medication, the study team will call every week for the first 2 months (excluding in-person visit weeks) to assess mood and safety. After the first 2 months, the study team will call the participant every two weeks in between in-person visits. Participants will be compensated for time spent in this study. Participants assigned to a study medication will also be given the option to participate in the open-label phase of the study, which involves 3 follow-up visits (weeks 24, 36, and 48) over 7 months after the 20-week trial. During this phase, participants can continue to take the medication through their clinical care provider.

Conditions

Bipolar I Disorder; Bipolar II Disorder; Schizo Affective Disorder; Obesity; Weight Loss; GLP - 1

Outcome Measures

Primary Outcomes (1)

• Describe the distribution of obesity phenotypes (hungry brain, hungry gut, emotional hunger and slow burn) in patients with BD and obesity, with the goal of identifying predominant phenotype patterns within this clinical population.

  From enrollment through the end of the 20-week intervention.

Secondary Outcomes (7)

• Compare the distribution of obesity phenotypes (hungry brain, hungry gut, emotional hunger, and slow burn) in patients with BD and obesity and non-BD participants published in previously cohorts.

  From the start of intervention (week 0) through the end of intervention (week 20).

• The feasibility and tolerability of anti-obesity medication (AOM) in patients with BD, assessed by adherence rates and reports on adverse events.

  from the start of intervention (week 0) through the end of intervention (week 20).

• Total body weight loss (in kilograms) from baseline to end point in patients with BD and obesity.

  From the start of intervention (week 0) through the end of intervention (week 20).

• The proportion of treatment responders, defined as individuals achieving >4% total body weight loss, from baseline to end point in patients with BD and obesity.

  From the start of intervention (week 0) through the end of intervention (week 20).

• Changes in metabolic parameters from baseline to end point in patients with BD.

  From the start of intervention (week 0) through the end of intervention (week 20).

Other Outcomes (3)

• Changes in mitochondrial biomarkers from baseline to end point in patients with BD and obesity.

  From the start of intervention (week 0) through the end of intervention (week 20)

• Changes in stress related biomarkers from baseline to end point in patients with BD and obesity.

  From the start of intervention (week 0) through the end of intervention (week 20)

• Surrogate biomarkers of obesity phenotypes.

  From the start of intervention (week 0) through the end of intervention (week 20).

Study Arms (4)

Semaglutide (Wegovy) + Group Therapy Program

EXPERIMENTAL

By meeting the satiety/return to hunger (Hungry Gut) phenotype, participants will take Semaglutide (Wegovy) and attend a 12-week group therapy session for the 16-week clinical trial.

Behavioral: Group Therapy Program; Drug: semaglutide

Naltrexone/Bupropion (Contrave) + Group Therapy Program

EXPERIMENTAL

By meeting the behavioral/psychological (Emotional Hunger) phenotype, participants will take Naltrexone/Bupropion (Contrave) and attend a 12-week group therapy session for the 16-week clinical trial.

Behavioral: Group Therapy Program; Drug: naltrexone and bupropion (combination)

Phentermine/Topiramate (Qsymia) + Group Therapy Program

EXPERIMENTAL

By meeting the satiation (Hungry Brain) phenotype, participants will take Phentermine/Topiramate (Qsymia) and attend a 12-week group therapy session for the 16-week clinical trial.

Behavioral: Group Therapy Program; Drug: Phentermine-Topiramate

No Study Medication + Group Therapy Program

EXPERIMENTAL

By meeting the slow burn phenotype, participants will attend a 12-week group therapy session for the 16-week clinical trial.

Behavioral: Group Therapy Program

Interventions

Group Therapy Program BEHAVIORAL

a 12-week group therapy program centered around weight loss and healthy eating.

Naltrexone/Bupropion (Contrave) + Group Therapy Program; No Study Medication + Group Therapy Program; Phentermine/Topiramate (Qsymia) + Group Therapy Program; Semaglutide (Wegovy) + Group Therapy Program

semaglutide DRUG

Brand name: Wegovy

Semaglutide (Wegovy) + Group Therapy Program

Phentermine-Topiramate DRUG

Brand name: Qsymia

Phentermine/Topiramate (Qsymia) + Group Therapy Program

naltrexone and bupropion (combination) DRUG

Brand name: Contrave

Naltrexone/Bupropion (Contrave) + Group Therapy Program

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women between 18 to 65 years old.
• Patients with a SCID IV confirmed diagnosis of bipolar disorder (BDI or BDII) or schizoaffective bipolar type (SZA-BD).
• Women with a negative pregnancy test 48 hours before study entry (obesity phenotyping visit).
• Patients with a negative urine drug screen except for allowable drugs.
• Patients with a BMI ≥ 30 kg/m2 or a BMI ≥ 27 kg/m2 plus one medical comorbidity (e.g., type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea)
• Patients must be undergoing mood stabilizer treatment but may also receive concurrent antidepressant or anxiolytic therapy.
• Patients must be on a stable regimen of a mood stabilizer, with no changes to the medication, for at least one month prior to study enrollment.
• Continuation of mood-stabilizing treatment is preferred but not required; the decision should be made in collaboration with the participant's primary mental health provider.

You may not qualify if:

• Abdominal bariatric surgery: Gastric bypass surgery (Roux-en-Y), Adjustable gastric band (Lap band), and Gastric sleeve surgery (Sleeve gastrectomy).
• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, such as diabetic gastroparesis; or use of medications that may alter gastrointestinal motility and appetite.
• Positive history of chronic gastrointestinal diseases that could affect gastrointestinal absorption such as inflammatory bowel disease (IBD), celiac disease, small intestinal bacterial overgrowth (SIBO), etc; or use of medications that may alter gastrointestinal absorption.
• Significant untreated psychiatric dysfunction.
• Hypersensitivity to any of the study medications.
• Contraindications to the FDA-approved medications: Phentermine-Topiramate Extended Release; Oral naltrexone extended-release/bupropion extended-release (NBSR; Contrave®, Mysimba™); and Semaglutide (Weygovy™).
• Inability to provide informed consent: participants who are on involuntary commitment, conservatorship or under a legal guardian.
• Patients with active hypomania or mania (YMRS ≥ 20 points)
• Patients with active psychosis (YMRS item 8 ≥ 6 points)
• Patients with active suicide ideation (MADRS item 10 ≥ 4 points)
• Patients with any medication changes (mood stabilizers) without advisement of study clinicians or clinical provider.
• Patients with active bulimia (purging) or anorexia (severe restriction)
• Patients with a history of bulimia (purging behaviors) or anorexia (severe dietary restriction) within the 12 months preceding study enrollment will be excluded
• Current drug and/or alcohol use disorders (except nicotine)
• Patients with a positive toxicology screening (except cannabis)

Sponsors & Collaborators

• Mayo Clinic: lead
• University of Toronto: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Psychotic Disorders; Obesity; Weight Loss

Interventions

semaglutide; Qsymia; Naltrexone-Bupropion combination

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Study Officials

• Mark A Frye, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura N Harper

CONTACT

507-255-9352; harper.laura1@mayo.edu

Karin M Lindstrom, Ph.D.

CONTACT

507-293-3876; lindstrom.karin@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: October 9, 2025
• Study Start: January 19, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)