Topiramate in Adolescents With Severe Obesity
Condition: Obesity, Morbid; Obesity; Weight Loss
MeSH terms: Obesity; Obesity, Morbid; Weight Loss
Intervention: Topiramate; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Topiramate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 34.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

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.
    

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