Effect of Continuous GHRP-3 Infusion at on GH-IGF-I System, Blood Pressure, Glucose, and Insulin Resistance

This study has been terminated.
(Inadequate subject recruitment)
Sponsor:
Information provided by (Responsible Party):
Tina Thethi, Tulane University Health Sciences Center
ClinicalTrials.gov Identifier:
NCT00846872
First received: February 17, 2009
Last updated: May 5, 2014
Last verified: May 2014
  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 Dysfunction
Drug: GHRP-3
Drug: Saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


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 ]

Enrollment: 4
Study Start Date: July 2008
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low dose GHRP-3
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
Other Names:
  • Formerly coded as 1485
  • Fourth generation growth hormone secretagogue
Active Comparator: High dose GHRP -3
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
Other Names:
  • Formerly coded as 1485
  • Fourth generation growth hormone secretagogue
Placebo Comparator: Saline Infusion
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.
Drug: Saline
5% mannitol will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr
Other Name: 5% mannitol

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:

  1. 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.
  2. 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.
  3. 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:

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

Exclusion Criteria:

  1. Patients taking medications that may alter carbohydrate metabolism and/or insulin resistance.
  2. Female patients with a positive pregnancy test.
  3. Previous history of hypersensitivity to GHRP.
  4. Patients with overt liver disease, renal disease and/or congestive heart failure.
  5. Patients with anticipated change in medication regimen during the study period.
  6. Current use or history of use of hormone replacement therapy in the last six months.
  7. Current use or history of use of Ace Inhibitors or Angiotensin receptor blockers in the last six months.
  8. Hemoglobin of < 11.6 g/dL for women and < 12.9 g/dL for men.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Louisiana
Clinical and Translational Research center Tulane Hospital
New Orleans, Louisiana, United States, 70112
Clinical and Translational Research Center, University Hospital
New Orleans, Louisiana, United States, 70112
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: Tina Thethi, MD, MPH, Tulane University Health Sciences Center
ClinicalTrials.gov Identifier: NCT00846872     History of Changes
Other Study ID Numbers: 65-08
Study First Received: February 17, 2009
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tulane University Health Sciences Center:
GHRP-3
Insulin Resistance
Markers of inflammation
Endothelial Dysfunction
Flow Mediated Dilation
GH/IGF-1 axis
Post menopausal

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hormones
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 22, 2014