Topiramate in Adolescents With Severe Obesity

NCT ID: NCT01859013

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2017-04-30

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).

Conditions

Obesity, Morbid; Obesity; Weight Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Topiramate

Intervention Type: DRUG

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.

Sugar Pill

Four (4) weeks of meal replacement therapy, followed by 28-weeks of placebo (sugar pill) therapy.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Topamax; Sugar Pill

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron S Kelly, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27807925 (View on PubMed)

Other Identifiers

1304M31241

Identifier Type: -

Identifier Source: org_study_id