Topiramate in Adolescents With Severe Obesity

Obesity Clinical Trial

Official title:

BMI Reduction With Meal Replacements + Topiramate in Adolescents With Severe Obesity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01859013
• Other study ID #: 1304M31241
• Status: Recruiting
• Phase: Phase 2
• First received: May 9, 2013
• Last updated: February 24, 2016
• Start date: June 2013
• Est. completion date: December 2017

Study information

• Verified date: February 2016
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: Cameron E Naughton, MPA
• Phone: 612-625-3623
• Email: naug0009[@]umn.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

The primary object is to evaluate the effect of meal replacement therapy followed by topiramate vs. meal replacement therapy followed by placebo on percent change in BMI among 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.

The secondary objective is to characterize the safety profile of topiramate for the treatment of adolescent obesity, evaluate the effects of meal replacement therapy followed by topiramate vs. meal replacement therapy followed by placebo on risk factors for CVD and T2DM, and evaluate response to topiramate treatment based on baseline eating behavior phenotype in adolescents with severe obesity. The secondary hypothesis is that 4 weeks of meal replacement therapy followed by 24 weeks of topiramate will significantly reduce average absolute BMI, absolute and percent body weight, percent total body and visceral fat, systolic blood pressure, fasting triglycerides and insulin, compared to meal replacement therapy followed by placebo, and that the presence of binge eating disorder characteristics at baseline will be associated with greater reduction in BMI with topiramate treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity
• Obesity, Morbid
• Weight Loss

Intervention

Drug:
• Topiramate
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. Patients who do not tolerate dose escalation will be reduced to the highest tolerated dose for the remainder of the trial.

Other:
• Placebo
Placebo will be taken orally once daily in the evening for the first two weeks, and orally twice daily (AM and PM) for the remainder of the study.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Body Mass Index at 28-Weeks	The Percent Change from Baseline in Body Mass Index at 28-Weeks	Baseline and 28-Weeks	No