Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy (CRANIOEXE)

University Hospital of Bordeaux

Status and phase: Completed; Phase 3

Conditions: Hypothalamic Obesity; Craniopharyngiomas

Treatments: Drug: Placebo; Drug: Exenatide

Study type: Interventional

Funder types: Other

Identifiers

NCT02860923

CHUBX 2012/17

Details and patient eligibility

About

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.

Full 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).

Enrollment: 42 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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42 participants in 2 patient groups, including a placebo group

Exenatide

Experimental group

Description:

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.

Treatment:

Drug: Exenatide

Placebo

Placebo Comparator group

Description:

Patients will be maintained on placebo (injected subcutaneously, twice a day) with the same dose and frequency than exenatide arm.

Treatment:

Drug: Placebo