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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypothalamic Obesity; Craniopharyngiomas
• Intervention / Treatment: Drug: Placebo; Drug: Exenatide

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).

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU d'Angers
  • Brest, France
    • CHU de Brest
  • Grenoble, France
    • CHU de Grenoble
  • Lyon, France
    • Chu de Lyon
  • Marseille, France
    • APHM
  • Paris, France
    • Hopital Cochin
  • Paris, France
    • Hopital Europeen Georges Pompidou
  • Paris, France
    • Hôpital Bicêtre
  • Paris, France
    • Hôpital Pitié Salpétrière (APHP)
  • Pessac, France
    • Hôpital Haut-Lévêque
  • Toulouse, France
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Exenatide
PLACEBO_COMPARATOR: Placebo; Patients will be maintained on placebo (injected subcutaneously, twice a day) with the same dose and frequency than exenatide arm.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment tolerance thanks to digestive parameters	Tolerance will be assessed by the presence of: - Nauseas, vomiting.	6 months
Treatment tolerance thanks to dermatologic parameter	Tolerance will be assessed by the presence of: - Injection-site symptoms.	6 months
Treatment tolerance thanks to pulse rate	Tolerance will be assessed by the presence of : - Increasing of pulse rate.	6 months
Treatment tolerance thanks to Beck scale	Tolerance will be assessed by the presence of : - Anxiety by Beck scale.	6 months
Treatment tolerance thanks to HAD scale	Tolerance will be assessed by the presence of : - depression evaluated by HAD scale.	6 months
Treatment tolerance thanks to enzymatic parameters	Tolerance will be assessed by the presence of : - Increasing of pancreatic enzymes.	6 months
Treatment tolerance thanks to glycemia parameter	Tolerance will be assessed by the presence of : - Hypoglycaemia	6 months
Assess cardiovascular risks thanks to glucose profil	Levels of blood glucose and insulin, oral glucose tolerance testing, haemoglobin A1C	6 months
Assess cardiovascular risks thanks to lipid profil	Levels of HDL cholesterol, triglycerides, LDL cholesterol.	6 months
Assess cardiovascular risks thanks to metabolic parameters	The metabolic parameters considered: - Body composition (Dual energy-ray absorptiometry) and abdominal obesity (waist circumference).	6 months
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
Assess eating behaviour thanks to energy intake		6 months
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
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
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
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
Assess energy expenditure thanks to physical activity	The energy expenditure will be estimated thanks to pedometer. - Resting metabolic rate (indirect calorimetry).	6 months
Assess energy expenditure thanks to indirect calorimetry	The energy expenditure will be estimated thanks to: - Resting metabolic rate	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Blandine Gatta-Cherifi, Pr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 11, 2017
• Primary Completion (ACTUAL): June 30, 2018
• Study Completion (ACTUAL): September 30, 2018

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (ESTIMATE): August 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: placebo; exenatide; multicenter trial; glucagon-like peptide-1
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Musculoskeletal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Bone Diseases; Bone Neoplasms; Obesity; Craniopharyngioma; Adamantinoma; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: CHUBX 2012/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO