Role of Growth Hormone Antagonism in Modulating Insulin Sensitivity in Subjects With Pre-diabetes

Diabetes Clinical Trial

— PEGIR  

Official title:

Role of Growth Hormone Antagonism in Modulating Insulin Sensitivity in Subjects With Insulin Resistance But Without Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02023918
• Other study ID #: WI178028
• Status: Completed
• Phase: Phase 2
• First received: December 24, 2013
• Last updated: April 20, 2017
• Start date: January 2014
• Est. completion date: December 2015

Study information

• Verified date: April 2017
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Growth hormone is well known to cause changes in glucose regulation. People with Laron syndrome are born without the growth hormone receptor and are protected from diabetes. Mice who are engineered without the growth hormone receptor are similarly protected from diabetes. Conversely, people who have excessive amounts of growth hormone, such as patients with acromegaly, have an increased risk for type 2 diabetes. In acromegaly patients, treatment with pegvisomant, a medication that reduces insulin like growth factor-1 by blocking the growth hormone receptor, significantly improves insulin resistance. Pegvisomant has not been explored as a possibility for the treatment of type 2 diabetes or insulin resistance in people without acromegaly. In this study, the investigators hope to study the metabolic effects of pegvisomant on people who have insulin resistance but not diabetes. Pegivosmant is expected to improve insulin resistance in the liver, fat and muscle as well as decrease serum free fatty acids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• BMI between 18-35

• Homeostatic model assessment - insulin resistance (HOMA-IR) >2.77

• Able to administer daily subcutaneous injections of pegvisomant

Exclusion Criteria:

• Pregnancy

• Breastfeeding in the last 6 months

• Liver function tests greater than 3x the upper limits of normal

• unstable diet over the last 3 months

• unstable weight over the last 6 months

• unstable lipid lowering regimen

• diabetes - type 1 or type 2

• History of major gastrointestinal surgery

• History of pancreatic, liver, biliary, or intestinal disease

• Fasting blood glucose >126

• Fasting triglycerides>500

• A1c>6.5

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Insulin Resistance
• Metabolic Syndrome
• Metabolic Syndrome X

Intervention

Drug:
• pegvisomant
Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	San Francisco General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Sensitivity	Investigators will measure insulin sensitivity via hyperinsulinemic euglycemic clamp prior to the initiation of the study medication and then again at the end of the 28 days to evaluate the effect of pegvisomant on insulin sensitivity and reported as HOMA-IR.; HOMA-IR was derived from fasting insulin and fasting glucose by the calculation: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5	28 days
Secondary	Lipolysis	Treatment with pegvisomant is expected to alter lipolysis. To assess this investigators will do fasting and steady state stable isotope measurements prior to treatment with pegvisomant and at day 28 after treatment with pegvisomant.	28 days