Hypothalamic Obesity Clinical Trial
— ECHOOfficial title:
Glucagon-Like Peptide-1 Agonist Effects on Energy Balance in Hypothalamic Obesity
Verified date | May 2022 |
Source | Seattle Children's Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 42 |
Est. completion date | July 31, 2020 |
Est. primary completion date | March 16, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 10 Years to 25 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospitals adn Clinics of Minnesota | Minneapolis | Minnesota |
United States | Vanderbilt University School of Medicine | Nashville | Tennessee |
United States | Seattle Childrens | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Seattle Children's Hospital | Children's Hospitals and Clinics of Minnesota, Vanderbilt University |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA) | Body composition change between baseline and the end of the 36-week randomized drug treatment phase assessed by dual energy x-ray absorptiometry (DEXA) and expressed as the change in adipose tissue mass. | At baseline and 36 weeks | |
Secondary | Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis. | Changes in fat and total calorie intake during free buffet meals assessed at baseline and after 36-weeks of study drug treatment.
The buffet meal is an objective measure of satiety as it assesses food intake and choice after a caloric preload. A standardized test meal preload provided 20% of estimated daily caloric requirements,based on the Schofield-HW equation. The purpose of the test meal is to ensure that study participants are in an equally fed state. Ninety minutes later, an ad libitum buffet meal was served consisting of a wide variety of food items and more than the child's estimated daily calorie requirements will be offered (5,000 kcal). Children had access to the buffet for 30 min, after which calorie intake and composition of consumed foods was measured by weighing back uneaten food. |
From baseline to 36 weeks | |
Secondary | Changes in Fasting Glucose | Change in fasting blood glucose between baseline and the end of the 36-week randomized drug treatment phase. | From baseline to 36 weeks | |
Secondary | Changes in HDL Cholesterol and Triglycerides Assessed by Fasting Lipids | Change in fasting HDL cholesterol and triglycerides between baseline and the end of the 36-week randomized drug treatment phase. | From baseline to 36 weeks | |
Secondary | Changes in Inflammation Assessed by C-reactive Protein (CRP) | Change in C-reactive protein (CRP) between baseline and the end of the 36-week randomized drug treatment phase. | From baseline to 36 weeks | |
Secondary | Changes of Insulin Resistance Assessed by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Changes of insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) using the formula HOMA-IR = insulin [mU/l] x glucose [mmol/l]) / 22.5 where both insulin and glucose values are obtained from a fasting blood sample. | From baseline to 36 weeks | |
Secondary | Changes of Circulating Leptin Levels | Change in circulating leptin between baseline and the end of the 36-week randomized drug treatment phase. | From baseline to 36 weeks | |
Secondary | Changes of Energy Expenditure Assessed by Doubly Labeled Water Analysis | Total energy expenditure in the free-living environment was measured using doubly labeled water which estimates carbon dioxide production by measuring the elimination of the tracers deuterium (²H) and oxygen-18 (¹8O) from the body. These measures are used to determine the average daily rate of carbon dioxide production which is then used to calculate total energy expenditure using an equation from Weir and an assumed food quotient (0.85). | Baseline and 36 weeks | |
Secondary | Changes of Energy Intake Assessed by Automated Self-Administered 24-Hour Dietary Recall (ASA24-Kids) | Self-reported daily energy intake was assessed by Automated Self-Administered 24-Hour Dietary Recall (ASA24-Kids, http://appliedresearch.cancer.gov/tools/instruments/asa24/), a web-based diet assessment tool that allows 24-hour diet recall using branded food items. | Baseline and 36 weeks | |
Secondary | Changes in Glucose 120 Minutes Following an Oral Glucose Tolerance Test | Change in blood glucose measures 120 minutes post-glucose bolus during an oral glucose tolerance test between baseline and the end of the 36-week randomized drug treatment phase. | From baseline to 36 weeks |
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