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

• Status: Completed
• Trial end date: 2020-07-31
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seattle Children's Hospital
• Collaborators: Children's Hospitals and Clinics of Minnesota; Vanderbilt University
• Treatments: Exenatide; Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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