Effect of Continuous Subcutaneous GHRP-3 Infusion at 2 Doses on the GH-IGF-I System, BP, Glucose, and Insulin Resistance - Full Text View

Sponsored by:	Tulane University Health Sciences Center
Information provided by:	Tulane University Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00846872

Purpose

The hypothesis is that GHRP-3 will exert beneficial effects on endothelial function and insulin resistance in older men and women via hormonal (GH, IGF-I, IGFBP-3,-1, insulin) and non-hormonal actions (anti-inflammatory).

Condition	Intervention	Phase
Insulin Resistance Endothelial Function	Drug: GHRP-3 Device: Saline	Phase I Phase II

Drug Information available for: Mannitol Insulin Insulin-like growth factor I Mecasermin rinfabate Somatotropin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Single Blind (Subject), Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	Effect of Continuous Subcutaneous GHRP-3 Infusion at 2 Dose Levels on the Physiological Secretion of the GH-IGF-I System, Blood Pressure, Glucose, Inflammatory Markers and Endothelial Function in Subjects With Insulin Resistance

Further study details as provided by Tulane University Health Sciences Center:

Primary Outcome Measures:

Determine the relative effects of 0.1µg/kg/h and 0.5µg/kg/h GHRP-3 as compared to placebo in inducing physiological secretion of the GH-IGF-I system after continuous sc delivery in healthy older men and women with insulin resistance [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine the relative interrelated effects of 0.1 and 0.5µg/kg/h GHRP-3 infusion and placebo on various hormonal and non hormonal aspects of insulin resistance. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	12
Study Start Date:	July 2008
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Active Comparator Subjects will receive the infusion for 14 ± 2 days. On day 1 of the test period, patients will report to the CTRC in a fasting state stay there for 3 - 4 hrs after the initiation of the infusion. Blood will be drawn in a fasting state and urine sample will be collected prior to insertion of the OmniPod and the CGMS. On day 7 +/- 2 days and on day 12 +/- 2 days, patients will report to the CTRC for blood draw and CGMS insertion. On day 14 +/- 2 days, patients will again report to CTRC for 24 hour admit. They will undergo urine sample collection, periodic blood draws and BP monitoring. After the 24 hour period, the CGMS will be disconnected and the patient will undergo FMD after which the test period will be terminated. There will be a washout period of 2 weeks between each test period.	Drug: GHRP-3 0.1 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr
3: Active Comparator Subjects will receive the infusion for 14 ± 2 days. On day 1 of the test period, patients will report to the CTRC in a fasting state stay there for 3 - 4 hrs after the initiation of the infusion. Blood will be drawn in a fasting state and urine sample will be collected prior to insertion of the OmniPod and the CGMS. On day 7 +/- 2 days and on day 12 +/- 2 days, patients will report to the CTRC for blood draw and CGMS insertion. On day 14 +/- 2 days, patients will again report to CTRC for 24 hour admit. They will undergo urine sample collection, periodic blood draws and BP monitoring. After the 24 hour period, the CGMS will be disconnected and the patient will undergo FMD after which the test period will be terminated. There will be a washout period of 2 weeks between each test period.	Drug: GHRP-3 0.5 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr
I: Placebo Comparator Subjects will receive Placebo for 14 ± 2 days. On day 1 of the test period, patients will report to the CTRC in a fasting state stay there for 3 - 4 hrs after the initiation of the infusion. Blood will be drawn in a fasting state and urine sample will be collected prior to insertion of the OmniPod and the CGMS. On day 7 +/- 2 days and on day 12 +/- 2 days, patients will report to the CTRC for blood draw and CGMS insertion. On day 14 +/- 2 days, patients will again report to CTRC for 24 hour admit. They will undergo urine sample collection, periodic blood draws and BP monitoring. After the 24 hour period, the CGMS will be disconnected and the patient will undergo FMD after which the test period will be terminated. There will be a washout period of 2 weeks between each test period.	Device: Saline 5% mannitol will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

Detailed Description:

At the lower dose of 0.1 µg/kg/h, GHRP-3 presumably will improve endothelial dysfunction, enhance insulin action and lower blood pressure via the anti-inflammatory effects of GHRP-3 while at the higher dose of 0.5 µg/kg/h GHRP-3 these anti-inflammatory effects will be further augmented by the hormonal action of increasing serum IGF-I and its primary serum binding protein insulin like growth hormone binding protein - 3 (IGFBP-3 as well as -1).

Also, the more detailed inter-relationships between the actions of GHRP-3, GH and IGF-I on serum glucose, blood pressure, and lipid levels over 24h periods will be determined at the end of the 14 day placebo and two GHRP-3 infusion periods. The GHRP-3 will be administered in escalating doses.

The Specific Aims of this study are as follows:

To determine the relative effects of 0.1µg/kg/h and 0.5µg/kg/h GHRP-3 as compared to placebo infusion in inducing physiological secretion of the GH-IGF-I system after continuous sc delivery for 14 days in healthy older men and women with insulin resistance.
To determine the relative interrelated effects of 0.1 and 0.5µg/kg/h GHRP-3 infusion and placebo on various hormonal and non hormonal aspects of insulin resistance such as blood pressure (BP), plasma glucose and FFA as well as GH, IGF-I, IGFBP-1, -3, insulin and endothelin-1 levels.
To determine the relative effects of placebo and the above 2 doses of GHRP-3 infusion on flow mediated dilation (FMD) and nitroglycerin-dependent dilation

Eligibility

Ages Eligible for Study:	45 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Men and post-menopausal women 50-70 years.
Elevated fasting plasma glucose ranging <125 mg/dL
Waist circumference >35 inches in women and >40 inches in men

Exclusion Criteria:

Patients taking medications that may alter carbohydrate metabolism and/or insulin resistance.
Female patients with a positive pregnancy test.
Previous history of hypersensitivity to GHRP.
Patients with overt liver disease, renal disease and/or congestive heart failure.
Patients with anticipated change in medication regimen during the study period.
Current use or history of use of hormone replacement therapy in the last six months.
Current use or history of use of Ace Inhibitors or Angiotensin receptor blockers in the last six months.
Hemoglobin of < 11.6 g/dL for women and < 12.9 g/dL for men.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846872

Contacts

Contact: Tina K Thethi, MD, MPH	504-988-5044	tthethi@tulane.edu
Contact: Jennifer J Kalarickal, MD	504-988-5990	jjohnkal@tulane.edu

Locations

United States, Louisiana
Clinical and Translational Research center Tulane Hospital	Recruiting
New Orleans, Louisiana, United States, 70112
Principal Investigator: Tina K Thethi, MD, MPH
Principal Investigator: Jennifer J Kalarickal, MD
Sub-Investigator: Vivian Fonseca, MD, FRCP
Sub-Investigator: Cyril Bowers, MD
Clinical and Translational Research Center, University Hospital	Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Virginia Garrison 504-988-4000 vgarris@tulane.edu
Contact: Mary Meyaski-Schluter 504-988-4000 mmeyask@tulane.edu
Principal Investigator: Tina K Thethi, MD, MPH
Principal Investigator: Jennifer J Kalarickal, MD
Sub-Investigator: Vivian Fonseca, MD, FRCP
Sub-Investigator: Cyril Bowers, MD

Sponsors and Collaborators

Tulane University Health Sciences Center

Investigators

Principal Investigator:	Tina K Thethi, MD, MPH	Tulane Universtiy Health Sciences Center
Principal Investigator:	Jennifer J Kalarickal, MD	Tulane University Health Sciences Center
Principal Investigator:	Vivian Fonseca, MD, FRCP	Tulane University Health Sciences Center
Principal Investigator:	Cyril Bowers, MD	Tulane University Health Sciences Center

More Information

No publications provided

Responsible Party:	Tulane University Health Sciences Center ( Tina Thethi, MD, MPH )
Study ID Numbers:	65-08
Study First Received:	February 17, 2009
Last Updated:	February 18, 2009
ClinicalTrials.gov Identifier:	NCT00846872 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Tulane University Health Sciences Center:

GHRP-3
Insulin Resistance
Markers of inflammation
Endothelial function

Flow Mediated Dilation
GH/IGF-1 axis
Post menopausal

Study placed in the following topic categories:

Hyperinsulinism
Metabolic Diseases
Dilatation, Pathologic
Mannitol
Insulin Resistance
Glucose Metabolism Disorders

Hormones
Metabolic Disorder
Insulin
Menopause
Inflammation

Additional relevant MeSH terms:

Hyperinsulinism
Metabolic Diseases
Insulin Resistance
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on May 07, 2009