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

NCT ID: NCT00846872

Last Updated: 2021-01-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2012-03-31

Brief Summary

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).

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

Conditions

Insulin Resistance; Endothelial Dysfunction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

GHRP-3 low dose

Intervention Type: DRUG

0.1 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

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.

Group Type: ACTIVE_COMPARATOR

GHRP-3 high dose

Intervention Type: DRUG

0.5 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

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.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

5% mannitol will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

Interventions

GHRP-3 low dose

0.1 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

Intervention Type: DRUG

GHRP-3 high dose

0.5 µg/kg/hr will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

Intervention Type: DRUG

Saline

5% mannitol will be infused subcutaneously in a continuous manner using the Omnipod at the rate of 28 µl/hr

Intervention Type: DRUG

Other Intervention Names

Formerly coded as 1485; Fourth generation growth hormone secretagogue; Formerly coded as 1485; Fourth generation growth hormone secretagogue; 5% mannitol

Eligibility 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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tulane University Health Sciences Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tina K Thethi, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

AdventHealth

Other Identifiers

65-08

Identifier Type: -

Identifier Source: org_study_id