Topiramate in Adolescents With Severe Obesity

Phase 2

Completed

Conditions: Obesity, Morbid
Obesity
Weight Loss

Interventions: Other: Placebo
Drug: Topiramate

Registration Number: NCT01859013

Lead Sponsor: University of Minnesota

Brief Summary: The prevalence of severe pediatric obesity is on the rise and youth with this condition are at elevated risk for developing chronic diseases such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Topiramate, a medication approved by the Food and Drug Administration (FDA) for the treatment of seizures in adults and children, is associated with weight loss. Although not FDA approved for the treatment of obesity, studies in obese adults have demonstrated weight reduction of approximately 5% with 6-12 months of therapy. However, the weight loss effect of topiramate has never been evaluated among children and adolescents. Therefore, the goal of this pilot study is to evaluate the safety and efficacy of 24 weeks of topiramate therapy with a 4-week run-in of meal replacement therapy in adolescents with severe obesity. The primary hypothesis is that 4 weeks of meal replacement therapy followed by 24 weeks of topiramate will have a larger average percent decline in BMI between baseline and 28 weeks compared to meal replacement therapy followed by placebo.

Detailed Description: The prevalence of severe pediatric obesity is on the rise and youth with this condition are at elevated risk for developing chronic diseases such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Lifestyle modification therapy alone is ineffective for most adolescents with severe obesity and few patients qualify for bariatric surgery. Many patients would likely benefit from pharmacotherapy but only one medication (orlistat) is approved for use in adolescents but notable side effects and limited efficacy impede its clinical use. Topiramate, a medication approved by the Food and Drug Administration (FDA) for the treatment of seizures in adults and children, is associated with weight loss. Although not FDA approved for the treatment of obesity, studies in obese adults have demonstrated weight reduction of approximately 5% with 6-12 months of therapy. However, the weight loss effect of topiramate has never been evaluated among children and adolescents. Therefore, the goal of this pilot study is to evaluate the safety and efficacy of 24 weeks of topiramate therapy with a 4-week run-in of meal replacement therapy in adolescents with severe obesity.

This will be a 28-week, randomized, double-blind, placebo-controlled, pilot clinical trial of meal replacement therapy (4 weeks) followed by topiramate (24 weeks) vs. meal replacement therapy (4 weeks) followed by placebo (24 weeks) for BMI reduction and cardiometabolic risk factor improvement in 36 adolescents (ages 12-17 years old) with severe obesity. Monthly lifestyle modification/behavioral counseling will be delivered by trained study coordinators to patients in both groups. The lifestyle modification education materials will be given to patients and selected sections will be discussed at each monthly contact (five face-to-face sessions and three phone sessions).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

BMI ≥1.2 times the 95th percentile (based on gender and age) or BMI ≥35 kg/m2
12-18 years old
Tanner stage IV or V by physical exam

Exclusion Criteria

Tanner stage I, II, or III
Type 1 or 2 diabetes mellitus
Previous (within 6-months) or current use of weight loss medication (patients may undergo washout)
Previous (within 6-months) or current use of drugs associated with weight gain (e.g. steroids/anti-psychotics)
Previous bariatric surgery
Recent initiation (within 3-months) of anti-hypertensive or lipid medication
Previous (within 6-months) or current use of medication to treat insulin resistance or hyperglycemia (patients may undergo washout)
Major psychiatric disorder
Females: Pregnant, planning to become pregnant, or unwilling to use 2 or more acceptable methods of contraception when engaging in sexual activity throughout the study
Tobacco use
Liver/renal dysfunction
- ALT or AST >2.5 times the upper limit of normal
- Bicarbonate <18 mmol/L
- Creatinine >1.2 mg/dL
Glaucoma
Obesity associated with genetic disorder (monogenetic obesity)
Hyperthyroidism or uncontrolled hypothyroidism
History of suicidal thought/attempts
History of kidney stones
History of cholelithiasis
Current use of other carbonic anhydrase inhibitor

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar Pill	Placebo	Four (4) weeks of meal replacement therapy, followed by 28-weeks of placebo (sugar pill) therapy.
Topiramate	Topiramate	Four (4) weeks of meal replacement therapy, followed by 28-weeks of topiramate therapy. Topiramate will be initiated at a dose of 25 mg (taken orally once daily in the evening), escalated to 50 mg (taken orally once daily in the evening) after 1 week, and escalated to 75 mg (taken orally 25 mg in the morning and 50 mg in the evening) after 2 weeks.

Primary Outcome Measures