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

What Was Tested

This registered phase 3 trial tested Exenatide for fat loss, obesity & body recomposition.

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).

It had two arms (groups): Exenatide once weekly extended-release (active comparator) and Matching placebo (placebo 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.

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

The registry classes the interventions as drug.

More on the Plan

Excessive weight gain and its cardiometabolic sequela are frequent complications of hypothalamic tumors, a condition known as hypothalamic obesity (HO).

Patients with CP typically become obese and have more features of the metabolic syndrome compared to matched controls.

Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways.

Recently, the investigators developed a semi-quantitative assessment of hypothalamic damage on brain magnetic resonance imaging (MRI) to predict the risk for HO development in CP.

Who Took Part

42 actual participants took part.

It was open to people of any sex aged from 10 years up to 25 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Age 10-25 years at time of enrollment. History of craniopharyngioma or another tumor located in the hypothalamic area. Hypothalamic lesion documented by neuroradiology. ≥ 6 months post-surgical or radiation treatment. Stable hormone replacement for at least 3 months prior to screening visit.

The full record lists 7 inclusion and 14 exclusion criteria; among the exclusions: 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; initiation of weight loss medications within 3 months of screening visit.

How the Study Was Run

Design: randomized, parallel-group and quadruple-blind.

The fat loss, obesity & body recomposition participants were allocated by chance, so the Exenatide group and the comparison group should start out alike.

Groups ran in parallel: each of the fat loss, obesity & body recomposition participants stayed in one arm throughout.

Neither the fat loss, obesity & body recomposition participants nor the staff measuring them knew who was on Exenatide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2016-03 with completion listed for 2020-03-16.

It ran at 3 sites in United States (3).

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Percent Change of Body Mass Index (BMI) as Calculated by the Formula: Body Weight in kg Divided by Height in Meters² (time frame: From baseline to 36 weeks).

It also tracked 10 secondary outcomes, for example Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA), Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis, Changes in Fasting Glucose, Changes in HDL Cholesterol and Triglycerides Assessed by Fasting Lipids, Changes in Inflammation Assessed by C-reactive Protein (CRP) and Changes of Insulin Resistance Assessed by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Exenatide in 42 people with fat loss, obesity & body recomposition.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the Exenatide compound page, Fat loss, obesity & body recomposition research.