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

Hypothalamic Obesity Clinical Trial

— CRANIOEXE  

Official title:

Multicentre Double-blind Randomized Clinical Trial Assessing Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02860923
• Other study ID #: CHUBX 2012/17
• Status: Completed
• Phase: Phase 3
• Start date: January 11, 2017
• Est. completion date: September 30, 2018

Study information

• Verified date: October 2018
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 30, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Craniopharyngioma
• Craniopharyngiomas
• Hypothalamic Obesity
• Obesity

Intervention

Drug:
• Exenatide

• Placebo

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Brest	Brest
France	CHU de Grenoble	Grenoble
France	CHU de Lyon	Lyon
France	APHM	Marseille
France	Hôpital Bicêtre	Paris
France	Hôpital Cochin	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Pitié Salpétrière (APHP)	Paris
France	Hôpital Haut-Lévêque	Pessac
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare body weight change thanks to weighing machine	The primary outcome will be assessed by a weighing machine that measure until 200 kg.	baseline and 6 months
Secondary	Treatment tolerance thanks to digestive parameters	Tolerance will be assessed by the presence of: - Nauseas, vomiting.	6 months
Secondary	Treatment tolerance thanks to dermatologic parameter	Tolerance will be assessed by the presence of: - Injection-site symptoms.	6 months
Secondary	Treatment tolerance thanks to pulse rate	Tolerance will be assessed by the presence of : - Increasing of pulse rate.	6 months
Secondary	Treatment tolerance thanks to Beck scale	Tolerance will be assessed by the presence of : - Anxiety by Beck scale.	6 months
Secondary	Treatment tolerance thanks to HAD scale	Tolerance will be assessed by the presence of : - depression evaluated by HAD scale.	6 months
Secondary	Treatment tolerance thanks to enzymatic parameters	Tolerance will be assessed by the presence of : - Increasing of pancreatic enzymes.	6 months
Secondary	Treatment tolerance thanks to glycemia parameter	Tolerance will be assessed by the presence of : - Hypoglycaemia	6 months
Secondary	Assess cardiovascular risks thanks to glucose profil	Levels of blood glucose and insulin, oral glucose tolerance testing, haemoglobin A1C	6 months
Secondary	Assess cardiovascular risks thanks to lipid profil	Levels of HDL cholesterol, triglycerides, LDL cholesterol.	6 months
Secondary	Assess cardiovascular risks thanks to metabolic parameters	The metabolic parameters considered: - Body composition (Dual energy-ray absorptiometry) and abdominal obesity (waist circumference).	6 months
Secondary	Assess eating behaviour thanks to physiological parameters	The eating behaviour will be evaluated by: - Plasma level of ghrelin measured after an overnight fast.	6 months
Secondary	Assess eating behaviour thanks to energy intake		6 months
Secondary	Assess eating behaviour thanks to Three factor eating	The eating behaviour will be evaluated by: - Scores of restriction, hunger and disinhibition (French version of the Three factor Eating Questionnaire).	6 months
Secondary	Assess eating behaviour thanks to visual analogic scales	The eating behaviour will be evaluated by: - Scores of desire to eat, hunger and fullness at visual analogic scales.	6 months
Secondary	Assess quality of life thanks to Beck questionnaire	The quality of life will be assessed by: - Scores of depression (short questionnaire of Beck).	6 months
Secondary	Assess quality of life thanks to ORWELL questionnaire	The quality of life will be assessed by: - Scores of quality of life (ORWELL questionnaire).	6 months
Secondary	Assess energy expenditure thanks to physical activity	The energy expenditure will be estimated thanks to pedometer.; - Resting metabolic rate (indirect calorimetry).	6 months
Secondary	Assess energy expenditure thanks to indirect calorimetry	The energy expenditure will be estimated thanks to: - Resting metabolic rate	6 months