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

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02023918
• Collaborator: San Francisco General Hospital (Other)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 23
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Metabolic Syndrome; Insulin Resistance	Drug: pegvisomant	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Role of Growth Hormone Antagonism in Modulating Insulin Sensitivity in Subjects With Insulin Resistance But Without Diabetes
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pegvisomant arm Pegvisomant 20 mg subcutaneously Qday x 28 days will be administered by the study subject.	Drug: pegvisomant; Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.; Other Names: Somavert

Outcome Measures

Primary Outcome Measures

1. Insulin Sensitivity [28 days]

   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

Secondary Outcome Measures

1. Lipolysis [28 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco General Hospital	San Francisco	California	United States	94110

Sponsors and Collaborators

• University of California, San Francisco
• San Francisco General Hospital

Investigators

• Principal Investigator: Ethan J Weiss, MD, University of California, San Francisco
• Principal Investigator: Morris Schambelan, MD, University of California, San Francisco
• Principal Investigator: Kathleen Mulligan, PhD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02023918
• Other Study ID Numbers: WI178028
• First Posted: Dec 30, 2013
• Last Update Posted: Apr 24, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by University of California, San Francisco: Growth hormone antagonism
• Additional relevant MeSH terms: Diabetes Mellitus; Metabolic Syndrome; Insulin Resistance

Study Results

Participant Flow

Arm/Group Title	Pegvisomant Arm
Arm/Group Description	Pegvisomant 20 mg subcutaneously Qday x 28 days will be administered by the study subject. pegvisomant: Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pegvisomant Arm
Arm/Group Description	pegvisomant: Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (3.6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Insulin Sensitivity
Description	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
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Patients were compared after treatment to their own baseline

Arm/Group Title	Pegvisomant Arm
Arm/Group Description	Pegvisomant 20 mg subcutaneously Qday x 28 days will be administered by the study subject.
Measure Participants	6
Baseline HOMA-IR	3.06 (1.46)
HOMA-IR after 28 days of treatment	3.33 (2.76)

2. Secondary Outcome

Title	Lipolysis
Description	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.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Ra glycerol reported

Arm/Group Title	Pegvisomant Arm
Arm/Group Description	Pegvisomant 20 mg subcutaneously Qday x 28 days will be administered by the study subject.
Measure Participants	6
Ra glycerol fasting state baseline	0.20 (0.07)
Ra glycerol fasting state after 28 days of peg	0.21 (0.02)
Ra glycerol steady state baseline	-0.01 (0.2)
Ra glycerol steady state treatment 28 days peg	0.4 (0.2)

Adverse Events

Arm/Group Title	Pegvisomant Arm
Arm/Group Description	pegvisomant: Pegvisomant 20 mg subcutaneously Qday will be administered by the study subject for 28 days during this study.
All Cause Mortality
	Pegvisomant Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pegvisomant Arm
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Pegvisomant Arm
	Affected / at Risk (%)	# Events
Total	0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.