Energy Balance & Weight Loss in Craniopharyngioma-related or Other Hypothalamic Tumors in Hypothalamic Obesity
Condition: Hypothalamic Obesity
MeSH terms: Obesity
Intervention: Exenatide; placebo
Intervention description: Weekly injections of active drug.; Weekly placebo injections
Intervention MeSH terms: Exenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 10 Years
Maximum age: 25 Years
Healthy volunteers: No
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

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).
    

Eligibility 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