Energy Balance & Weight Loss in Craniopharyngioma-related or Other Hypothalamic Tumors in Hypothalamic Obesity

NCT02664441 | Completed Phase 3 Results DMC

• 1 other identifier: R01DK104936-01A1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

The proposed multicenter study will test the effect of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (ExQW, Bydureon®) on clinical outcomes and metabolic parameters in a double-blind, placebo-controlled 36 week randomized trial with an 18 week open label extension. Following baseline testing, 48 patients will be randomly assigned with equal allocation to ExQW or matching placebo injection for 36 weeks, followed by an 18 week open label extension during which all patients receive ExQW. Changes of weight status, body composition, free-living total daily energy expenditure (EE) by doubly labeled water (DLW), activity by acetimetry, energy intake (questionnaires and food diary), as well as glucose tolerance and hormonal parameters of energy homeostasis and insulin resistance will be assessed before treatment and at the end of the placebo-controlled phase (week 36). Activity, metabolic outcomes, energy intake will be also assessed at study week 18 (mid treatment of randomized study), as well as week 54 (end of open label treatment).

Conditions

Hypothalamic Obesity

Keywords

Obesity; Drug intervention; Children; Adolescents; Young adults; Hypothalamic lesion; Change of weight status; Food intake; Energy expenditure; Hormonal changes; Glucagon-like peptide-1 agonist; Bydureon; Weight Loss; Energy balance

Outcome Measures

Primary Outcomes (1)

• Percent Change of Body Mass Index (BMI) as Calculated by the Formula: Body Weight in kg Divided by Height in Meters².

  Percent change of body mass index (BMI), as calculated by the formula: body weight in kg divided by height in meters², between baseline and the end of the 36-week randomized drug treatment phase.

  From baseline to 36 weeks

Secondary Outcomes (10)

• Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)

  At baseline and 36 weeks

• Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis.

  From baseline to 36 weeks

• Changes in Fasting Glucose

  From baseline to 36 weeks

• Changes in HDL Cholesterol and Triglycerides Assessed by Fasting Lipids

  From baseline to 36 weeks

• Changes in Inflammation Assessed by C-reactive Protein (CRP)

  From baseline to 36 weeks

Study Arms (2)

Exenatide once weekly extended-release

ACTIVE COMPARATOR

Injections of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (Bydureon®) for 36 weeks in randomized intervention followed by 18 weeks open label exenatide once weekly extended-release.

Drug: Exenatide

Matching placebo

PLACEBO COMPARATOR

Weekly injections of placebo for 36 weeks followed by 18 weeks open label exenatide once weekly extended-release.

Drug: placebo

Interventions

Exenatide DRUG

Weekly injections of active drug.

Also known as: Bydureon®

Exenatide once weekly extended-release

placebo DRUG

Weekly placebo injections

Matching placebo

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 10-25 years at time of enrollment
• Diagnosis of hypothalamic obesity with age- and sex adjusted BMI ≥ 95% or BMI ≥30 kg/m² if over 18 y
• History of craniopharyngioma or another tumor located in the hypothalamic area
• Hypothalamic lesion documented by neuroradiology
• ≥ 6 months post-surgical or radiation treatment
• Weight stable or increasing over 3 months prior to screening visit
• Stable hormone replacement for at least 3 months prior to screening visit

You may not qualify if:

• Renal impairment (GFR\<60 ml/min/1.73m² using the Schwarz formula)
• History of gastroparesis; pancreatitis or gallstones (unless status post cholecystectomy)
• Family history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma metabolic disorders
• Any insulin-treated diabetes mellitus, poorly controlled type 2 diabetes (HbA1c ≥ 10%), or any other chronic serious medical conditions such as cardiovascular disease, malignancy or hematologic disorder, complicated syndromic disorder, or psychiatric disorders (schizophrenia, major depression, history of suicide attempts)
• Calcitonin \>50 mg/L at screening
• Initiation of weight loss medications within 3 months of screening visit
• Previous donation of blood \>10% of estimated blood volume within 3 months prior study
• Current warfarin use
• Current use of any other GLP1 receptor agonist
• Untreated thyroid disorder or adrenal insufficiency
• History of bariatric surgery or planned bariatric surgery until end of study
• Pregnancy, lactation or expectation to conceive during study period
• Subject unlikely to adhere to study procedures in opinion of investigator
• Subject with contraindication to neuroimaging by MRI

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Children's Hospitals and Clinics of Minnesota: collaborator
• Vanderbilt University: collaborator

Study Sites (3)

Children's Hospitals adn Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37235, United States

Location

Seattle Childrens

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Sexual Infantilism; Obesity; Weight Loss

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Christian L. Roth, MD
• Organization: Seattle Children's Hospital

christian.roth@seattlechildrens.org

206-987-5428

Study Officials

• Christian Roth, MD

  Seattle Childrens

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 27, 2016
• Study Start: March 1, 2016
• Primary Completion: March 16, 2020
• Study Completion: July 31, 2020
• Last Updated: May 5, 2022
• Results First Posted: May 5, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)