Clinical trial NCT02273804: Topiramate and Severe Obesity
Official title: Topiramate and Severe Obesity in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obese Children and Adolescents
Keywords: Topiramate
Obesity
Children
Adolescents
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2014-10-24
Enrollment: 18
Sex: ALL
Minimum age (years): 9
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Percent Change from Baseline in Body Mass Index (BMI)
timeFrame: 9 months
Secondary outcomes:
measure: Adverse event outcome
timeFrame: Up to 4,5 years of follow-up
measure: Percent Change from Baseline in Body Mass Index Z-score
timeFrame: 9 months
measure: Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score
timeFrame: 1 months
measure: Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score
timeFrame: 3 months
measure: Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score
timeFrame: 4 months
measure: Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score
timeFrame: 6 months
measure: Eating Behaviour
timeFrame: 6 months
measure: Eating Behaviour
timeFrame: 9 months
measure: Physical activity
timeFrame: 6 months
measure: Physical activity
timeFrame: 9 months
measure: Food intake
timeFrame: 6 months
measure: Food intake
timeFrame: 9 months
measure: Comorbidity outcome
timeFrame: 6 months
measure: Comorbidity outcome
timeFrame: 9 months
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Hopital Bicêtre
state: Paris
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marie-Laure Frelut, MD
role: STUDY_CHAIR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Gianpaolo De Filippo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.