Obesity Clinical Trial
Official title:
Role of Pharmacotherapy in Counteracting Weight Regain in Adolescents With Severe Obesity
Long-term weight loss maintenance is seldom achieved by individuals with obesity owing to numerous biological adaptations occurring in the post-weight loss setting, including neuroendocrine-mediated changes in appetite/satiety and reduction of energy expenditure. Following weight loss, peripheral and central mechanisms respond in a way similar to starvation by conveying a sense that energy reserves have dwindled, activating a strong counter-response to increase caloric intake. Moreover, metabolic rate drops, further compounding the propensity for weight rebound. Adolescents with severe obesity are not immune to the vexing issue of weight regain; therefore, effective and scalable treatments are urgently needed. Pharmacotherapy has the potential to prevent weight regain by targeting counter-regulatory mechanisms in the post-weight loss setting. Unfortunately, only one obesity medication is FDA-approved for long-term use in adolescents and is seldom prescribed owing to modest efficacy and notable side effects. Among the most promising candidates in the pediatric pipeline is the combination of phentermine and topiramate, which is the most effective adult weight loss medication currently available. The mechanisms of action are thought to reduce appetite, enhance satiety, and potentially increase energy expenditure, making this medication particularly well-suited for the purpose of weight loss maintenance since it targets many of the biological adaptations known to induce relapse and subsequent weight regain. The investigators have generated preliminary data demonstrating that both phentermine and topiramate reduce BMI in adolescents with severe obesity and have acceptable safety profiles. In this clinical trial, the investigators will utilize combination phentermine/topiramate to target counter-regulatory pathways responsible for weight regain after meal replacement therapy (structured meals of known caloric content) in adolescents with severe obesity with a goal of enhancing weight loss maintenance and improving obesity-related complications. Importantly, the investigators will maximize the clinical utility and overall impact of the study by comprehensively characterizing the safety of phentermine/topiramate utilizing sensitive measures of cardiac autonomic function, arterial stiffness, cognition, and bone health as well as examine the extent to which this medication counteracts mechanisms of weight regain.
Status | Recruiting |
Enrollment | 143 |
Est. completion date | June 30, 2026 |
Est. primary completion date | June 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years to 18 Years |
Eligibility | Inclusion Criteria: - Severe obesity (BMI >/= 120% of the 95th percentile or BMI >/= 35 kg/m2) - Age 12 to < 18 years of age at enrollment (screening) and Tanner stage >/= 2 - Female participants who are sexually active with males and who are able to get pregnant must agree to use two forms of contraception throughout the trial Exclusion Criteria: - Diabetes (type 1 or 2) - Current or recent (< six months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination phentermine/topiramate, liraglutide, and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion) - Previous metabolic/bariatric surgery - Current use of a stimulant medication - History of glaucoma - Current or recent (<14 days) use of monoamine oxidase inhibitor - Known hypersensitivity to sympathomimetic amines - Any history of treatment with growth hormone - Any history of bulimia nervosa - Major psychiatric disorder as determined by the local medical monitor - Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression - Any history of active suicide attempt - History of suicidal ideation or self-harm within the previous 30 days of screening - PHQ-9 score >15 at screening - Current pregnancy or plans to become pregnant during study participation - Current tobacco use - ALT or AST >/= 3 times the upper limit of normal - Bicarbonate <18 mmol/L - Creatinine > 1.2 mg/dL - Any history of seizures - Uncontrolled hypertension as determined by the local medical monitor - History of structural heart defect or clinically significant arrhythmia - Diagnosed monogenic obesity - Any history of cholelithiasis - Any history of nephrolithiasis - Clinically diagnosed hyperthyroidism - Untreated thyroid disorder - Any disorder, unwillingness, or inability, not covered by any other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol |
Country | Name | City | State |
---|---|---|---|
United States | University of Minnesota | Minneapolis | Minnesota |
Lead Sponsor | Collaborator |
---|---|
University of Minnesota |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To measure changes in BMI. | The investigators will measure the change in BMI reduction during the meal replacement therapy intervention as well as during the treatment with phentermine/topiramate or placebo. Weight and height will be combined to report BMI in kg/m^2 | 58 weeks. | |
Primary | To measure changes in total body fat | The investigators will measure the change in total body fat during the meal replacement therapy intervention and during the treatment with phentermine/topiramate or placebo via use of dual-energy x-ray absorptiometry (iDXA). | iDXA will be conducted at four timepoints (Baseline, 1 day of Randomization, Week 26 and Week 52). | |
Primary | To measure changes in visceral fat. | The investigators will measure the change in visceral fat during the meal replacement therapy intervention and during the treatment with phentermine/topiramate or placebo via use of the iDXA. | iDXA will be conducted at four timepoints (Baseline, 1 day of Randomization, Week 26 and Week 52). | |
Primary | To measure changes in lipids. | Lipids (consisting of total lipids, LDL, HDL, cholesterol and triglycerides) | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. | |
Primary | To measure changes in glucose. | The investigators will track whether fasting glucose levels come down during the course of participation in the study. Glucose can be an indicator of diabetes. Typical fasting glucose ranges for individuals 6 months and older are approximately 70-99 mg/dL. Investigators will track whether glucose levels reduce during the course of the study. | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. | |
Primary | To measure changes in insulin. | Investigators will track whether insulin levels reduce during the course of the study. | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. | |
Primary | To measure changes in hemoglobin A1c. | Investigators will track whether hemoglobin A1c levels (which can indicate pre-diabetes or diabetes) decrease during the course of the study. Normal ranges for hemoglobin A1c are less than 5/7%. Prediabetes ranges are 5.7-7.5% and diabetes ranges are 6.5% or greater. | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. | |
Primary | To measure changes in C-reactive protein (CRP). | C-reactive protein tests help to measure cardiac risk. Investigators will review C-reactive protein levels during the study to see if they decrease. Normal ranges for CRP are: <1 mg/L for low risk, 1.0-3.0 mg/L for average risk, >3.0 mg/L for high risk and > 10.0 mg/L for acute inflammation. | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. | |
Primary | To measure changes in oxidized LDL. | Investigators will measure changes in oxidized low-density lipoprotein. Oxidized LDL is a potentially harmful cholesterol that is produced in the body when normal LDL cholesterol is damaged by chemical interactions. | Baseline, 1 day of Randomization, Week 26 and Week 52 visits. |
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