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

Primary Purpose

Craniopharyngiomas, Hypothalamic Obesity

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Exenatide
Placebo
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Craniopharyngiomas focused on measuring glucagon-like peptide-1, exenatide, placebo, multicenter trial

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • CHU d'Angers
  • CHU de Brest
  • CHU de Grenoble
  • CHU de Lyon
  • APHM
  • Hôpital Bicêtre
  • Hôpital Cochin
  • Hôpital Européen Georges Pompidou
  • Hôpital Pitié Salpétrière (APHP)
  • Hôpital Haut-Lévêque
  • CHU de Toulouse

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Exenatide

Placebo

Arm 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.

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

Outcomes

Primary Outcome Measures

Compare body weight change thanks to weighing machine
The primary outcome will be assessed by a weighing machine that measure until 200 kg.

Secondary Outcome Measures

Treatment tolerance thanks to digestive parameters
Tolerance will be assessed by the presence of: - Nauseas, vomiting.
Treatment tolerance thanks to dermatologic parameter
Tolerance will be assessed by the presence of: - Injection-site symptoms.
Treatment tolerance thanks to pulse rate
Tolerance will be assessed by the presence of : - Increasing of pulse rate.
Treatment tolerance thanks to Beck scale
Tolerance will be assessed by the presence of : - Anxiety by Beck scale.
Treatment tolerance thanks to HAD scale
Tolerance will be assessed by the presence of : - depression evaluated by HAD scale.
Treatment tolerance thanks to enzymatic parameters
Tolerance will be assessed by the presence of : - Increasing of pancreatic enzymes.
Treatment tolerance thanks to glycemia parameter
Tolerance will be assessed by the presence of : - Hypoglycaemia
Assess cardiovascular risks thanks to glucose profil
Levels of blood glucose and insulin, oral glucose tolerance testing, haemoglobin A1C
Assess cardiovascular risks thanks to lipid profil
Levels of HDL cholesterol, triglycerides, LDL cholesterol.
Assess cardiovascular risks thanks to metabolic parameters
The metabolic parameters considered: - Body composition (Dual energy-ray absorptiometry) and abdominal obesity (waist circumference).
Assess eating behaviour thanks to physiological parameters
The eating behaviour will be evaluated by: - Plasma level of ghrelin measured after an overnight fast.
Assess eating behaviour thanks to energy intake
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).
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.
Assess quality of life thanks to Beck questionnaire
The quality of life will be assessed by: - Scores of depression (short questionnaire of Beck).
Assess quality of life thanks to ORWELL questionnaire
The quality of life will be assessed by: - Scores of quality of life (ORWELL questionnaire).
Assess energy expenditure thanks to physical activity
The energy expenditure will be estimated thanks to pedometer. - Resting metabolic rate (indirect calorimetry).
Assess energy expenditure thanks to indirect calorimetry
The energy expenditure will be estimated thanks to: - Resting metabolic rate

Full Information

First Posted
June 24, 2016
Last Updated
October 11, 2018
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT02860923
Brief Title
Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy
Acronym
CRANIOEXE
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
January 11, 2017 (Actual)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
September 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Craniopharyngiomas, Hypothalamic Obesity
Keywords
glucagon-like peptide-1, exenatide, placebo, multicenter trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Perez, Dr
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Blandine Gatta-Cherifi, Pr
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU d'Angers
City
Angers
Country
France
Facility Name
CHU de Brest
City
Brest
Country
France
Facility Name
CHU de Grenoble
City
Grenoble
Country
France
Facility Name
CHU de Lyon
City
Lyon
Country
France
Facility Name
APHM
City
Marseille
Country
France
Facility Name
Hôpital Bicêtre
City
Paris
Country
France
Facility Name
Hôpital Cochin
City
Paris
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
Country
France
Facility Name
Hôpital Pitié Salpétrière (APHP)
City
Paris
Country
France
Facility Name
Hôpital Haut-Lévêque
City
Pessac
Country
France
Facility Name
CHU de Toulouse
City
Toulouse
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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