Topiramate and Severe Obesity (TOBI)

Topiramate and Severe Obesity in Children and Adolescents

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.

Study Overview

• Status: Completed
• Conditions: Obese Children and Adolescents
• Intervention / Treatment: Drug: Topiramate; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris
    • Le Kremlin-Bicêtre, Paris, France, 94275
      • Hôpital Bicêtre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: topiramate; pill	Drug: Topiramate; 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.
Placebo Comparator: placebo; Sugar pill	Drug: Placebo; Placebo will be taken orally following to the same dose regimen according to theoretical weight

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Marie-Laure Frelut, MD, Assistance Publique - Hôpitaux de Paris; Principal Investigator: Gianpaolo De Filippo, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• McGovern L, Johnson JN, Paulo R, Hettinger A, Singhal V, Kamath C, Erwin PJ, Montori VM. Clinical review: treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials. J Clin Endocrinol Metab. 2008 Dec;93(12):4600-5. doi: 10.1210/jc.2006-2409. Epub 2008 Sep 9.
• Bray GA. Risks of obesity. Endocrinol Metab Clin North Am. 2003 Dec;32(4):787-804, viii. doi: 10.1016/s0889-8529(03)00067-7.
• Astrup A, Caterson I, Zelissen P, Guy-Grand B, Carruba M, Levy B, Sun X, Fitchet M. Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects. Obes Res. 2004 Oct;12(10):1658-69. doi: 10.1038/oby.2004.206.
• Toplak H, Hamann A, Moore R, Masson E, Gorska M, Vercruysse F, Sun X, Fitchet M. Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Int J Obes (Lond). 2007 Jan;31(1):138-46. doi: 10.1038/sj.ijo.0803382. Epub 2006 May 16.
• Rosenstock J, Hollander P, Gadde KM, Sun X, Strauss R, Leung A; OBD-202 Study Group. A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of topiramate controlled release in the treatment of obese type 2 diabetic patients. Diabetes Care. 2007 Jun;30(6):1480-6. doi: 10.2337/dc06-2001. Epub 2007 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): December 21, 2017
• Study Completion (Actual): January 23, 2018

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 22, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Adolescents; Obesity; Children; Topiramate
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: P091122; 2011-006193-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No