Topiramate and Severe Obesity

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of Topiramate on the decrease of Body Mass Index compared to placebo at 9 months.

Detailed Description
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Childhood obesity remains through adulthood in main cases, and is associated with an early increase of cardiovascular risk and an excess mortality in young adults due to stroke and cancer. Bariatric surgery is very rare in France for children and can cause severe complications. Long term effects are still unknown. Topiramate is already use in thousands of children in neurology, its effects are already well known, and no lethal complication is reported. The hypothesis is that Topiramate associated with standard treatment of obesity is more effective than standard treatment alone. This will be a 4.5-years, randomized, double-blind, placebo-controlled, clinical trial of topiramate (9 months) vs placebo (9months) for Body Mass Index reduction in 160 adolescents (ages 9-17 years old) with severe obesity. The main objective is to evaluate the efficacy of Topiramate on the decrease of Body Mass Index compared to placebo at 9 months. The secondary objectives are to evaluate: the decrease of Body Mass Index Z-score the tolerance of Topiramate the effectiveness of Topiramate on weight decrease and decrease of Body Mass Index and Body Mass Index Z-score at 1, 3 ,4 and 6 months the effectiveness of Topiramate on eating behaviour, physical activity, calculated with validated questionnaires and scales at 6 and 9 months the pharmacokinetic of Topiramate in obese children and adolescents

Official Title
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Topiramate and Severe Obesity in Children and Adolescents

Conditions
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Obese Children and Adolescents

Intervention / Treatment
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* Drug: Topiramate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 9-17 years old Body Mass Index Z-score ≥ 4 SD of French reference Weight at enrolment ≥ 50 kg Therapeutic failure > 6 months For girls of childbearing age, willing to have an acceptable method of contraception (no estrogens plus progestin) Negative pregnancy test for girls of childbearing age Agreeing to participate upon written informed consent Appropriate understanding of the study Exclusion Criteria: Syndromic or secondary obesity Major neurological or psychiatric disorder Current or history of suicidal thought/attempts Current or history of breakdown Previous bariatric surgery Severe hypercapnia Renal dysfunction Deformity in the urinary tract or solitary kidney History of renal lithiasis or glaucoma Poorly controlled diabetic children or adolescents (HbA1c >10%) and diabetic patients treated with Metformine and/or glibenclamide Hepatic dysfunction Bicarbonate ≤16 mmol/L Known hypersensitivity to the active substance or to one of the excipients Intolerance to saccharose Enrolment in another therapeutic study High probability to fail to comply with treatment Females: Pregnant, planning to become pregnant No signature on consent form Uncovered by the French National health Insurance system (Sécurité sociale)

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: topiramate<br>pill | Drug: Topiramate<br>* Topiramate for 9 months treatment, and then 27 months of follow-up Dose regimen will be determined according to theoretical weight (taken orally), escalated every 15 days. Patients who do not tolerate dose escalation will be reduced to the highest tolerated dose.<br>|
| Placebo Comparator: placebo<br>Sugar pill | Drug: Placebo<br>* Placebo will be taken orally following to the same dose regimen according to theoretical weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Body Mass Index (BMI) | Success is defined by a percent change > 2.5% | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event outcome |  | Up to 4,5 years of follow-up | 
| Percent Change from Baseline in Body Mass Index Z-score |  | 9 months | 
| Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score |  | 1 months | 
| Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score |  | 3 months | 
| Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score |  | 4 months | 
| Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score |  | 6 months | 
| Eating Behaviour | Self-administered questionnaires and scales : Binge Eating Scale ; State trait anxiety Inventory for Children; Child depression inventory, Child Behavior Checklist | 6 months | 
| Eating Behaviour | Self-administered questionnaires and scales : Binge Eating Scale ; State trait anxiety Inventory for Children; Child depression inventory; Child Behavior Checklist | 9 months | 
| Physical activity | Questionnaire from French Ministry of Health | 6 months | 
| Physical activity | Questionnaire from French Ministry of Health | 9 months | 
| Food intake | High-fat, sugary, salted food intake and beverage other than drinking water | 6 months | 
| Food intake | High-fat, sugary, salted food intake and beverage other than drinking water | 9 months | 
| Comorbidity outcome | Comorbidities and metabolic and cardiorespiratory complications | 6 months | 
| Comorbidity outcome | Comorbidities and metabolic and cardiorespiratory complications | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Topiramate, Obesity, Children, Adolescents