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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus; Hypothalamic Obesity
• Intervention / Treatment: Drug: Exenatide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhang z yun; Phone Number: 86-21-52888286

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Department of Endocrinology and Metabolism
      • Contact: Ye h ying; Phone Number: 86-21-52887027
      • Sub-Investigator: Zhang z yun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide; 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 8 weeks	Drug: Exenatide; 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 8 weeks; Other Names: Byetta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Li yi ming, Huashan Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Anticipated): January 1, 2015
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: December 25, 2012
• First Submitted That Met QC Criteria: February 1, 2013
• First Posted (Estimate): February 5, 2013

Study Record Updates

• Last Update Posted (Estimate): October 22, 2013
• Last Update Submitted That Met QC Criteria: October 20, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Diabetes Mellitus; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 2012-217