Effects of Exenatide on Obesity and/or Diabetes Mellitus Due to Hypothalamic Damage

Study Overview
=================
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.

Official Title
-----------------
Effects of Exenatide on Obesity and/or Diabetes Mellitus Due to Hypothalamic Damage

Conditions
-----------------
Hypothalamic Obesity, Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Exenatide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be between 18 and 55 years old; Greater than 6 months post-treatment (including surgery, radiotherapy or chemotherapy) of craniopharyngioma or other diseases in the hypothalamic region; BMI≧28kg/m2 and/or diabetes mellitus; Greater than 3 months after adequate replacement therapy for hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-thyroid (HPT) axis; Sign informed consent document. Exclusion Criteria: Less than 6 months post surgery or radiotherapy or chemotherapy for craniopharyngioma or other diseases in the hypothalamic region; Inadequate replacement for the HPA axis and HPT axis or undertaking adjustments of the kind or dose of the substitutive medicine; Use of weight loss drugs or initiation of a weight loss program within past 3 months; Use of GLP-1 agonists or analogues or dipeptidyl peptidase IV (DPP-IV) inhibitors within past 3 months; History of bariatric surgery; Diagnosed with simple obesity or diabetes mellitus prior to the hypothalamic disorders, and those diagnosed with type 1 diabetes mellitus; With end-stage-renal diseases or history of kidney transplant or complicated with acute/chronic kidney failure (GFR≦30ml/min); History of inflammatory bowel diseases or gastroparesis or other gastric mortility problems; History of pancreatitis or chronic cholecystitis; History of allergic reaction to exenatide or other medication components; Undertaking warfarin; Pregnant or lactating women; Are participating in, or have participated in other drug clinical trials within past 3 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br>5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 8 weeks | Drug: Exenatide<br>* 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 8 weeks<br>* Other names: Byetta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight frome baseline to end of the study. |  | 3 months | 
| BMI |  | baseline and 3 months | 
| HbA1c |  | baseline and 3 months | 
| Blood glucose level. |  | 3 months. | 
| Beta cell function. |  | baseline and 3 months | 
| Insulin sensitivity. |  | baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waistline |  | baseline and 3 months | 
| Ratio of body fat |  | baseline and 3 months | 
| The amount of daily energy intake |  | baseline and 3 months | 
| Resting energy expenditure (kcals per day) |  | baseline and 3 months | 
| Grade of metabolic equivalents (MET) scales |  | baseline and 3 months | 
| Hipline. |  | baseline and 3 months | 
| waistline/hipline ratio |  | baseline and 3 months |