Clinical trial NCT00846872: Effect of Continuous GHRP-3 Infusion at on GH-IGF-I System, Blood Pressure, Glucose, and Insulin Resistance
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Insulin Resistance
Endothelial Dysfunction
Keywords: GHRP-3
Insulin Resistance
Markers of inflammation
Endothelial Dysfunction
Flow Mediated Dilation
GH/IGF-1 axis
Post menopausal
Lead sponsor: Tulane University
Sponsor class: OTHER
First posted: 2009-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

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.

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: 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.
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: AdventHealth
name: Tina K Thethi, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: