Clinical trial NCT02860923: Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy
Official title: Multicentre Double-blind Randomized Clinical Trial Assessing Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Craniopharyngiomas
Hypothalamic Obesity
Keywords: glucagon-like peptide-1
exenatide
placebo
multicenter trial
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2016-08-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This hypothalamic obesity is associated with serious metabolic and psychosocial consequences.

The purpose of the study is to compare the change of body weight after 6 months treatment with a lifestyle intervention + exenatide compare to the one after the same lifestyle intervention+ placebo in adults patients suffering from a hypothalamic obesity due to treatment of craniopharyngioma.

Detailed description: The development of glucagon-like peptide-1 (GLP-1) analogues might be a solution since native GLP-1 suppresses appetite and energy intake in both normal weight and obese individuals as well as in people with type 2 diabetes and delays gastric emptying. The underlying mechanisms that mediate the effects of weight involve not only central regions like the hypothalamus and the solitary tractus nucleus and area postrema but also peripheral regions as the gastrointestinal tract. These extra hypothalamic effects are of particular interest in the cases of obesity due to hypothalamic lesions.

Exenatide is a glucagon-like peptide-1 (GLP-1) analogue with a high structural homology to human GLP-1, a gut derived incretin hormone. Since exenatide causes a dose-dependent weight loss, decreasing concentration of glycosylated haemoglobin as well as improving ß-cell function and systolic blood pressure, it could be an attractive treatment for both type 2 diabetes and obesity. In a double-blind placebo-controlled 24-week trial, it has been recently shown that non diabetic obese patients maintained on exenatide 10µg x 2/j lost significantly more weight than did those on placebo (5.1 kg versus 1.6).

Eligibility criteria: Inclusion Criteria:

* They are between 18 and 75 yrs.
* They had been diagnosed with a craniopharyngioma treated by surgery and/or irradiation without sign of recurrence.
* They have a BMI upper than 30kg/m² with intractable weight gain following therapy for craniopharyngioma.
* They demonstrate at least one other endocrinopathy, as a marker of hypothalamic damage.
* All pituitary deficiencies are correctly treated.
* They gave their written, informed consent before the beginning of the study.

Exclusion Criteria:

* They have type 1 diabetes.
* They have type 2 diabetes treated with insulin.
* Acidocetosis.
* Bariatric surgery
* Previous personal history of thyroid or pancreatic cancer.
* Hypercalcitoninemia.
* They have been previously treated by GLP1 analogs.
* Hypertriglyceridemia upper than 5g/l
* They had previously demonstrated voluntary weight loss during the three previous months.
* They are under the age of 18 years or over the age of 65 yrs.
* They are maintained on medical treatment against obesity.
* They are receiving supraphysiologic hydrocortisone therapy (upper than 30 mg/jour).
* Their GH status change during the course of the study.
* Exenatide is contraindicated.
* Psychological and/or medical problems that would create difficulties for the patient to comply with the study protocol are present.

Primary outcomes:
measure: Compare body weight change thanks to weighing machine
timeFrame: baseline and 6 months
Secondary outcomes:
measure: Treatment tolerance thanks to digestive parameters
timeFrame: 6 months
measure: Treatment tolerance thanks to dermatologic parameter
timeFrame: 6 months
measure: Treatment tolerance thanks to pulse rate
timeFrame: 6 months
measure: Treatment tolerance thanks to Beck scale
timeFrame: 6 months
measure: Treatment tolerance thanks to HAD scale
timeFrame: 6 months
measure: Treatment tolerance thanks to enzymatic parameters
timeFrame: 6 months
measure: Treatment tolerance thanks to glycemia parameter
timeFrame: 6 months
measure: Assess cardiovascular risks thanks to glucose profil
timeFrame: 6 months
measure: Assess cardiovascular risks thanks to lipid profil
timeFrame: 6 months
measure: Assess cardiovascular risks thanks to metabolic parameters
timeFrame: 6 months
measure: Assess eating behaviour thanks to physiological parameters
timeFrame: 6 months
measure: Assess eating behaviour thanks to energy intake
timeFrame: 6 months
measure: Assess eating behaviour thanks to Three factor eating
timeFrame: 6 months
measure: Assess eating behaviour thanks to visual analogic scales
timeFrame: 6 months
measure: Assess quality of life thanks to Beck questionnaire
timeFrame: 6 months
measure: Assess quality of life thanks to ORWELL questionnaire
timeFrame: 6 months
measure: Assess energy expenditure thanks to physical activity
timeFrame: 6 months
measure: Assess energy expenditure thanks to indirect calorimetry
timeFrame: 6 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Brest
country: France
facility: CHU de Brest
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: CHU de Lyon
city: Marseille
country: France
facility: APHM
city: Paris
country: France
facility: Hôpital Bicêtre
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Pitié Salpétrière (APHP)
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital, Bordeaux
name: Paul Perez, Dr
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux
name: Blandine Gatta-Cherifi, Pr
role: PRINCIPAL_INVESTIGATOR
References: