Clinical trial NCT01859013: Topiramate in Adolescents With Severe Obesity
Official title: BMI Reduction With Meal Replacements + Topiramate in Adolescents With Severe Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity, Morbid
Obesity
Weight Loss
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2013-05-21
Enrollment: 34
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Body Mass Index at 28-Weeks
timeFrame: Baseline and 28-Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Aaron S Kelly, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fox CK, Kaizer AM, Rudser KD, Nathan BM, Gross AC, Sunni M, Jennifer Abuzzahab M, Schwartz BL, Kumar S, Petryk A, Billington CJ, Ryder JR, Kelly AS. Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial. Obesity (Silver Spring). 2016 Dec;24(12):2553-2561. doi: 10.1002/oby.21633. Epub 2016 Nov 3.