Topiramate in Adolescents With Severe Obesity

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01859013
First received: May 9, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Obesity, Morbid
Obesity
Weight Loss
Drug: Topiramate
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: BMI Reduction With Meal Replacements + Topiramate in Adolescents With Severe Obesity

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Percent Change from Baseline in Body Mass Index at 28-Weeks [ Time Frame: Baseline and 28-Weeks ] [ Designated as safety issue: No ]
    The Percent Change from Baseline in Body Mass Index at 28-Weeks


Estimated Enrollment: 36
Study Start Date: June 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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 Name: Topamax
Placebo Comparator: Sugar Pill
Four (4) weeks of meal replacement therapy, followed by 28-weeks of placebo (sugar pill) therapy.
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.
Other Name: Sugar Pill

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).

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.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01859013

Contacts
Contact: Cameron E Naughton, MPA 612-625-3623 naug0009@umn.edu
Contact: Ann E Sheldon, B.S. 612-624-3137 shel0230@umn.edu

Locations
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Cameron E Naughton, MPA    612-625-3623    naug0009@umn.edu   
Contact: Ann E Sheldon, B.S.    612-624-3137    shel0230@umn.edu   
Principal Investigator: Aaron S Kelly, Ph.D.         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Aaron S Kelly, Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01859013     History of Changes
Other Study ID Numbers: 1304M31241
Study First Received: May 9, 2013
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Obesity
Obesity, Morbid
Weight Loss
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Body Weight Changes
Topiramate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on September 30, 2014