Topiramate and Severe Obesity

Obese Children and Adolescents Clinical Trial

— TOBI  

Official title:

Topiramate and Severe Obesity in Children and Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273804
• Other study ID #: P091122
• Secondary ID: 2011-006193-36
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2016
• Est. completion date: January 23, 2018

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 23, 2018
• Est. primary completion date: December 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Obese Children and Adolescents
• Obesity
• Obesity, Morbid

Intervention

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
Placebo will be taken orally following to the same dose regimen according to theoretical weight

Locations

Country	Name	City	State
France	Hopital Bicêtre	Le Kremlin-Bicêtre	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

Bray GA. Risks of obesity. Endocrinol Metab Clin North Am. 2003 Dec;32(4):787-804, viii. Review. — View 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. Review. — View 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. Epub 2007 Mar 15. — View 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. Epub 2006 May 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Body Mass Index (BMI)	Success is defined by a percent change > 2.5%	9 months
Secondary	Adverse event outcome		Up to 4,5 years of follow-up
Secondary	Percent Change from Baseline in Body Mass Index Z-score		9 months
Secondary	Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score		1 months
Secondary	Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score		3 months
Secondary	Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score		4 months
Secondary	Percent Change from Baseline in Body Mass Index and Body Mass Index Z-score		6 months
Secondary	Eating Behaviour	Self-administered questionnaires and scales : Binge Eating Scale ; State trait anxiety Inventory for Children; Child depression inventory, Child Behavior Checklist	6 months
Secondary	Eating Behaviour	Self-administered questionnaires and scales : Binge Eating Scale ; State trait anxiety Inventory for Children; Child depression inventory; Child Behavior Checklist	9 months
Secondary	Physical activity	Questionnaire from French Ministry of Health	6 months
Secondary	Physical activity	Questionnaire from French Ministry of Health	9 months
Secondary	Food intake	High-fat, sugary, salted food intake and beverage other than drinking water	6 months
Secondary	Food intake	High-fat, sugary, salted food intake and beverage other than drinking water	9 months
Secondary	Comorbidity outcome	Comorbidities and metabolic and cardiorespiratory complications	6 months
Secondary	Comorbidity outcome	Comorbidities and metabolic and cardiorespiratory complications	9 months