Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy
- Conditions
- CraniopharyngiomasHypothalamic Obesity
- Interventions
- Drug: Placebo
- Registration Number
- NCT02860923
- Lead Sponsor
- University Hospital, Bordeaux
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exenatide Exenatide Treatment with exenatide at the initial dose of 5 µg x 2/day (subcutaneously administered) during 4 weeks, and treatment with 10 µg x 2/day during 5 months. Placebo Placebo Patients will be maintained on placebo (injected subcutaneously, twice a day) with the same dose and frequency than exenatide arm.
- Primary Outcome Measures
Name Time Method Compare body weight change thanks to weighing machine baseline and 6 months The primary outcome will be assessed by a weighing machine that measure until 200 kg.
- Secondary Outcome Measures
Name Time Method Assess eating behaviour thanks to Three factor eating 6 months The eating behaviour will be evaluated by:
- Scores of restriction, hunger and disinhibition (French version of the Three factor Eating Questionnaire).Assess eating behaviour thanks to visual analogic scales 6 months The eating behaviour will be evaluated by:
- Scores of desire to eat, hunger and fullness at visual analogic scales.Assess quality of life thanks to Beck questionnaire 6 months The quality of life will be assessed by:
- Scores of depression (short questionnaire of Beck).Assess quality of life thanks to ORWELL questionnaire 6 months The quality of life will be assessed by:
- Scores of quality of life (ORWELL questionnaire).Assess energy expenditure thanks to physical activity 6 months The energy expenditure will be estimated thanks to pedometer.
- Resting metabolic rate (indirect calorimetry).Treatment tolerance thanks to glycemia parameter 6 months Tolerance will be assessed by the presence of :
- HypoglycaemiaAssess cardiovascular risks thanks to metabolic parameters 6 months The metabolic parameters considered:
- Body composition (Dual energy-ray absorptiometry) and abdominal obesity (waist circumference).Treatment tolerance thanks to digestive parameters 6 months Tolerance will be assessed by the presence of:
- Nauseas, vomiting.Treatment tolerance thanks to Beck scale 6 months Tolerance will be assessed by the presence of :
- Anxiety by Beck scale.Treatment tolerance thanks to HAD scale 6 months Tolerance will be assessed by the presence of :
- depression evaluated by HAD scale.Assess cardiovascular risks thanks to lipid profil 6 months Levels of HDL cholesterol, triglycerides, LDL cholesterol.
Assess eating behaviour thanks to energy intake 6 months Treatment tolerance thanks to dermatologic parameter 6 months Tolerance will be assessed by the presence of:
- Injection-site symptoms.Treatment tolerance thanks to pulse rate 6 months Tolerance will be assessed by the presence of :
- Increasing of pulse rate.Treatment tolerance thanks to enzymatic parameters 6 months Tolerance will be assessed by the presence of :
- Increasing of pancreatic enzymes.Assess cardiovascular risks thanks to glucose profil 6 months Levels of blood glucose and insulin, oral glucose tolerance testing, haemoglobin A1C
Assess eating behaviour thanks to physiological parameters 6 months The eating behaviour will be evaluated by:
- Plasma level of ghrelin measured after an overnight fast.Assess energy expenditure thanks to indirect calorimetry 6 months The energy expenditure will be estimated thanks to:
- Resting metabolic rate
Trial Locations
- Locations (11)
Hôpital Pitié Salpétrière (APHP)
🇫🇷Paris, France
CHU de Toulouse
🇫🇷Toulouse, France
Hôpital Bicêtre
🇫🇷Paris, France
CHU de Brest
🇫🇷Brest, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
CHU de Grenoble
🇫🇷Grenoble, France
CHU d'Angers
🇫🇷Angers, France
APHM
🇫🇷Marseille, France
Hôpital Haut-Lévêque
🇫🇷Pessac, France
CHU de Lyon
🇫🇷Lyon, France
Hôpital Cochin
🇫🇷Paris, France