Double-blinded, 6 Months Study With Bydureon® or Placebo in Adolescents With Obesity to Explore Changes in BMI (Combat-JUDO)

• ClinicalTrials.gov Identifier: NCT02794402
• Recruitment Status: Completed
• First Posted: June 9, 2016
• Last Update Posted: May 18, 2022
• Sponsor: Uppsala University
• Information provided by (Responsible Party): Peter Bergsten, Uppsala University

Study Description

Brief Summary:

Combat-JUDO (Combating Juvenile Diabetes and Obesity through normalization of beta-cell function) is part of a collaborative project funded by the Seventh Framework Programme of the European Commission aiming to develop innovative therapeutic strategies by increasing pharmacology-based alternatives targeting insulin hypersecretion for the treatment of young obese individuals.

The prevalence of childhood obesity is ranging between 5-25% in Europe. The reason behind these alarming figures is mostly a changing environment with a more sedative lifestyle and supply of excess food. However, specific gene mutations have also been linked to obesity and new genes are continuously being discovered. There are very few effective means of intervention in children with obesity available today. Obesity is closely associated with a number of related metabolic diseases and some children with obesity develop the metabolic syndrome at an early stage in life. Individuals with obesity have an increased risk of developing type 2 diabetes mellitus (T2DM) and with the current increase in childhood obesity, some children will develop T2DM already in their adolescent years with huge impact on their long-term health and life expectancy.

Lifestyle modification interventions, including behavioural treatment, diet modification and physical activity, are cornerstones of primary and secondary prevention/treatment of pediatric obesity today. Exenatide is a GLP-1 (glucagon-like peptide-1) receptor agonist approved for use in adults with T2DM to improve glycemic control. A pilot study with exenatide treatment in non-diabetic children and adolescents with severe obesity showed a reduced BMI of approximately 5% and improved markers of insulin resistance and β-cell function were observed.

The Combat-JUDO study is a parallel, double-blind, randomized study comparing lifestyle intervention + exenatide 2 mg vs lifestyle and intervention + placebo in adolescents with obesity. The lifestyle intervention includes regular nutritional and psychological support at 4 occasions during the study as well as physical activity on a weekly basis. Exenatide/placebo is given as a subcutaneous injection once weekly for 24 weeks. The primary objective of the study is to compare the change in BMI-SDS (according to WHO) from baseline to the 6 months visit between the two treatment arms.

The study includes males and females of age 10-18 years and 5 months with BMI SDS >2.0 or age-adapted BMI >30 kg/m2.

Condition or disease	Intervention/treatment	Phase
Obesity	Drug: Exenatide; Behavioral: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Parallel, Double-blinded, Randomized, 6 Months, Two Arms Study With Lifestyle Intervention and Bydureon® or Lifestyle Intervention and Placebo in Adolescents With Obesity to Explore Differences With Regard to Change in BMI SDS
• Actual Study Start Date: September 2015
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bydureon; s.c. once Weekly	Drug: Exenatide; Bydureon (Exenatide once weekly) injections s.c.
Placebo Comparator: Placebo; s.c. once Weekly	Behavioral: Placebo; Placebo once weekly injections sc

Outcome Measures

Primary Outcome Measures :

1. BMI SDS (Body Mass Index Standard Deviation Score) [ Time Frame: 6 months ]
   The primary objective is to compare the change from baseline to the 6 months visit, between lifestyle intervention + exenatide 2 mg once weekly and lifestyle intervention + placebo, in BMI SDS (according to WHO) for adolescents with obesity.

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Signed informed consent prior to any study-specific procedures.
2. Males or females of age 10-18 years and 5 months.
3. Obesity (BMI SDS > 2.0 or age-adapted BMI > 30 kg/m2), according to WHO.

4. Not sexually active or usage of adequate anticonception. Female subjects must also have negative pregnancy tests. Methods that can achieve a failure rate of less than 1% per year (Pearl index <1), when used consistently and correctly, are considered as highly effective birth control methods. Such methods include:

   • Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

     • oral
     • intravaginal
     • transdermal

   • Progestogen-only hormonal contraception associated with inhibition of ovulation:

     • oral
     • injectable
     • implantable
   • Intrauterine device (IUD)
   • Intrauterine hormone-releasing system (IUS)
   • Bilateral tubal occlusion
   • Vasectomised partner Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject). 5. Ability to understand and comply with the requirements of the study.

Exclusion Criteria:

1. Known syndromal obesity, such as Prader-Willi syndrome, Laurence-Moon syndrome or Bardet-Biedl syndrome.
2. Pregnancy or lactation.
3. Indigestion-causing diseases.
4. Severe gastrointestinal disease.
5. Total or partial gastric or small intestine resection.
6. Type 1 or Type 2 diabetes mellitus.
7. Kidney disease (acute or chronic, according to physician (Creatinin/Urea/Cystatin-C for Schwartz Calculation)).
8. Hypo-/Hyperthyroidism, unless under stable treatment.
9. Severe Vitamin D insufficiency, unless under stable treatment.
10. Abnormal QT interval.
11. Clinically significant abnormal laboratory values, e.g. Triglycerides > 400 mg/dl (Salzburg) or > 4,5 mmol/L (Uppsala), Amylase > 300 U/L (Salzburg) or > 5,1 µkat/L (Uppsala), Lipase > 180 U/L (Salzburg) or > 15 µkat/L (Uppsala) or Calcitonin > 11.7 pg/ml (Salzburg) or > 3,4 pmol/L (Uppsala) for females and > 17 pg/ml (Salzburg) or > 5,0 pmol/L (Uppsala) for males.
12. Severe depression, severe anxiety or other psychiatric disorder referred to or undergoing special treatment, as judged by the investigator.
13. Severe sleep apnea (defined clinically).
14. Chronic diseases, as judged by the investigator.
15. Metformin treatment within 3 months prior to screening or concomitant medication influencing blood glucose (e.g. metformin and acarbose), influencing other parameters of metabolic syndrome (e.g. orlistat) or interfering with the investigational medicinal product.
16. Steroid treatment (oral or injected).
17. Concomitant medication addressing attention disorders.
18. Antidepressants that can lead to weight gain, as judged by the investigator.
19. Hypersensitivity to exenatide or to any of the excipients.
20. Pacemaker or metal implant that may interfere with Magnetic Resonance Imaging (MRI).
21. Claustrophobia (Uppsala and Salzburg) or abdominal diameter exceeding an MR gantry diameter of 70 cm (Salzburg).
22. Current or prior (within 3 months) participation in another clinical study involving an Investigational Medicinal Product (IMP).
23. A personal or family history of Medullary Thyroid Carcinoma (MTC)
24. A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Contacts and Locations

Locations

Austria

Department of Pediatrics, Salzburg State Hospital, Paracelsus Medical University

Salzburg, Austria, 5020

Sweden

Uppsala University Hospital

Uppsala, Sweden, 75185

Sponsors and Collaborators

Uppsala University

Investigators

• Principal Investigator: Anders Forslund, Assoc Prof; Uppsala University Hospital

More Information

• Responsible Party: Peter Bergsten, Professor, Uppsala University
• ClinicalTrials.gov Identifier: NCT02794402
• Other Study ID Numbers: 2015-001628-45
• First Posted: June 9, 2016
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

Additional relevant MeSH terms:

Obesity; Exenatide; Anti-Obesity Agents; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists