Clinical trial NCT01783717: Effects of Exenatide on Obesity and/or Diabetes Mellitus Due to Hypothalamic Damage
Official title: Effects of Exenatide on Obesity and/or Diabetes Mellitus Due to Hypothalamic Damage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypothalamic Obesity
Diabetes Mellitus
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2013-02-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the effect of exenatide on body weight and glycemic control in subjects with obesity and/or diabetes mellitus due to hypothalamic damage.

Detailed description: Patients with hypothalamus lesion caused by tumors in the hypothalamic region, such as craniopharyngioma and germ cell tumors, and inflammatory diseases are susceptible to develop severe obesity and diabetes mellitus. The occurrence of hypothalamic obesity in patients after surgery with or without radiotherapy for craniopharyngioma can be as high as 42-66%, and the incidence of type 2 diabetes mellitus of them is twice as much as healthy controls. Treatment of obesity and diabetes mellitus in this population is crucial for increasing morbidity and mortality. However, diet and exercise intervention has been proven useless in previous studies. Safe and effective medicine remains to be developed. Exenatide, a GLP-1 receptor agonist, which play an antihyperglycemic role through a variety of mechanisms, such as enhancing glucose-dependent insulin secretion, increasing beta cell mass and decreasing glucagon secretion, possesses a potent ability to induce satiety, slow gastric emptying and reduce food intake, resulting in weight loss both in diabetics and patients with simple obesity. Previous animal study has already shown GLP-1 agonist exendin-4 leads to reduction of weight and caloric intake in a rat model of hypothalamic obesity. Therefore, the investigators hypothesize exenatide treatment might lead to weight loss in hypothalamic obese patients and improve their glycemic control.

Eligibility criteria: Inclusion Criteria:

1. Be between 18 and 55 years old;
2. Greater than 6 months post-treatment (including surgery, radiotherapy or chemotherapy) of craniopharyngioma or other diseases in the hypothalamic region;
3. BMI≧28kg/m2 and/or diabetes mellitus;
4. Greater than 3 months after adequate replacement therapy for hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-thyroid (HPT) axis;
5. Sign informed consent document.

Exclusion Criteria:

1. Less than 6 months post surgery or radiotherapy or chemotherapy for craniopharyngioma or other diseases in the hypothalamic region;
2. Inadequate replacement for the HPA axis and HPT axis or undertaking adjustments of the kind or dose of the substitutive medicine;
3. Use of weight loss drugs or initiation of a weight loss program within past 3 months;
4. Use of GLP-1 agonists or analogues or dipeptidyl peptidase IV (DPP-IV) inhibitors within past 3 months;
5. History of bariatric surgery;
6. Diagnosed with simple obesity or diabetes mellitus prior to the hypothalamic disorders, and those diagnosed with type 1 diabetes mellitus;
7. With end-stage-renal diseases or history of kidney transplant or complicated with acute/chronic kidney failure (GFR≦30ml/min);
8. History of inflammatory bowel diseases or gastroparesis or other gastric mortility problems;
9. History of pancreatitis or chronic cholecystitis;
10. History of allergic reaction to exenatide or other medication components;
11. Undertaking warfarin;
12. Pregnant or lactating women;
13. Are participating in, or have participated in other drug clinical trials within past 3 months.

Primary outcomes:
measure: Change in body weight frome baseline to end of the study.
timeFrame: 3 months
measure: BMI
timeFrame: baseline and 3 months
measure: HbA1c
timeFrame: baseline and 3 months
measure: Blood glucose level.
timeFrame: 3 months.
measure: Beta cell function.
timeFrame: baseline and 3 months
measure: Insulin sensitivity.
timeFrame: baseline and 3 months
Secondary outcomes:
measure: Waistline
timeFrame: baseline and 3 months
measure: Ratio of body fat
timeFrame: baseline and 3 months
measure: The amount of daily energy intake
timeFrame: baseline and 3 months
measure: Resting energy expenditure (kcals per day)
timeFrame: baseline and 3 months
measure: Grade of metabolic equivalents (MET) scales
timeFrame: baseline and 3 months
measure: Hipline.
timeFrame: baseline and 3 months
measure: waistline/hipline ratio
timeFrame: baseline and 3 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Li yi ming
role: PRINCIPAL_INVESTIGATOR
References: