Research of Exenatide for Overweight/Obese PCOS Patients With IGR

Overweight and Obesity Clinical Trial

Official title:

Research of Exenatide for Management of Reproductive and Metabolic Dysfunction in Overweight/Obese PCOS Patients With Impaired Glucose Regulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03352869
• Other study ID #: [2017]077
• Status: Completed
• Phase: Phase 4
• Start date: November 28, 2017
• Est. completion date: July 31, 2018

Study information

• Verified date: September 2019
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Compare the therapeutic effects of exenatide, metformin and their combination for 3 months on reproductive and metabolic improvements of overweight/obese PCOS patients with impaired glucose regulation.

Description:

The investigators designed a randomized control trial to compare the therapeutic effects of exenatide, metformin and their combination for 3 months on reproductive and metabolic improvements of overweight/obese PCOS patients with impaired glucose regulation. The investigators plan to enroll 183 patients. Inclusion criteria: 1) Patients who have PCOS which is diagnosed according to 2003 Rotterdam criteria; 2) Overweight / obesity diagnostic criteria is based on WHO-WPR; 3) IGR diagnostic criteria is based on 1999 WHO diagnostic criteria; 4) have been treated with dietary and behavioral intervention for 3 months but are ineffective; 5) have no use of other hypoglycemic drugs before 3 months of treatment.

Patients with serious complications (cardiovascular events and recent significant liver, kidney or lung disease within 3 months); high blood pressure (>160/100mmHg); active infection; secondary diabetes; pregnancy; alcohol abuse; allergic to GLP-1 receptor agonist or metformin are excluded.

Then the investigators plan to randomly divide the 183 patients into 3 groups: exenatide group, metformin group, and combination group, with 61 samples for each group. Each group use specific treatment (showed as the group name) for 3 months. Before and after the intervention, the blood samples would be collected to detect blood glucose, insulin, lipid profile, sex hormones, blood chemistry for liver and kidney function, hsCRP etc., as well as the anthropometric measurement and image examinations. All patients discontinue after 12 weeks of treatment and only routine lifestyle intervention is performed after that. All patients receive 75 g OGTT test and insulin releasing test again 12 weeks after drug withdrawal to observe the IGR remission rate. To accurately assess the insulin secretion of islet β-cell, 13 patients would be randomly selected from MET group and from EX group respectively to receive the two-step hyperglycemic clamp before the intervention and after 12-week treatment.

The investigators will compare the data and finally identify the treatment effect of exenatide on PCOS patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: July 31, 2018
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. have PCOS which is diagnosed according to 2003 Rotterdam criteria;

2. overweight / obesity diagnostic criteria is based on WHO-WPR ;

3. IGR diagnostic criteria is based on 1999 WHO diagnostic criteria;

4. have been treated with dietary and behavioral intervention for 3 months but are ineffective;

5. have no use of other hypoglycemic drugs before 3 months of treatment.

Exclusion Criteria:

• Except for serious complications (cardiovascular events and recent significant liver, kidney or lung disease within 3 months)

• high blood pressure (>160/100mmHg)

• active infection

• secondary diabetes

• pregnancy

• alcohol abuse

• allergic to GLP-1 receptor agonist or metformin

Related Conditions & MeSH terms

• Disorder of Glucose Regulation
• Overweight
• Overweight and Obesity
• Polycystic Ovary Syndrome

Intervention

Drug:
• Exenatide
Use Exenatide for 3 months to treat PCOS
• Metformin
Use Metformin for 3 months to treat PCOS

Locations

Country	Name	City	State
China	Renji Hospital Department of Endocrinology and Metabolism	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Jul;93(7):2670-8. doi: 10.1210/jc.2008-0115. Epub 2008 May 6. — View Citation

Jensterle M, Kocjan T, Kravos NA, Pfeifer M, Janez A. Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome. Endocr Res. 2015;40(3):133-8. doi: 10.3109/07435800.2014.966385. Epub 2014 Oct 20. — View Citation

Jensterle M, Kravos NA, Goricar K, Janez A. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. BMC Endocr Disord. 2017 Jan 31;17(1):5. doi: 10.118 — View Citation

Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar. — View Citation

Kahal H, Abouda G, Rigby AS, Coady AM, Kilpatrick ES, Atkin SL. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2014 Oct;81(4):523-8. doi: 10.1111/cen.12369. Epub 2013 Dec 12. — View Citation

Kahal H, Aburima A, Ungvari T, Rigby AS, Coady AM, Vince RV, Ajjan RA, Kilpatrick ES, Naseem KM, Atkin SL. The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls. BMC Endocr Disord. 2015 Apr 2;15:14. doi: 10.1186/s12902-015-0005-6. — View Citation

Vitek W, Alur S, Hoeger KM. Off-label drug use in the treatment of polycystic ovary syndrome. Fertil Steril. 2015 Mar;103(3):605-11. doi: 10.1016/j.fertnstert.2015.01.019. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of intravenous blood glucose from impaired glucose regulation to normal glucose regulation	To compare the intravenous blood glucose of three groups 12 weeks after withdrawal. All patients discontinue after 12 weeks of treatment and only routine lifestyle intervention is performed after that. All patients receive 75 g OGTT test and insulin releasing test again 12 weeks after drug withdrawal to observe the IGR remission rate. To accurately assess the insulin secretion of islet ß-cell, 13 patients would be randomly selected from MET group and from EX group respectively to receive the two-step hyperglycemic clamp before the intervention and after 12-week treatment. Remission rate = Number of patients who has normal glucose tolerance 12 weeks after withdrawal / Number of patients who completed treatments × 100%	up to 12 weeks
Secondary	Improvement of hyperandrogenism	To compare the free androgen index (FAI =total serum testosterone x 100 / Sex Hormone Binding Globulin) of three groups after 12-week treatment	up to 12 weeks
Secondary	Improvement of blood lipid	To compare the circulating lipid level(triglyceride, total cholesterol, HDL-C, LDL-C, etc.) of three groups after 12-week treatment	up to 12 weeks
Secondary	Improvement of fatty liver	To compare the number of fatty liver patients diagnosed by ultrasonography of three groups after 12-week treatment	up to 12 weeks