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Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women

Primary Purpose

Hypercholesterolemia, Postmenopause

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
L-arginine
Estrogen
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring Adhesion Molecules, Endothelial Function, Inflammation, Lipoproteins, Nitric Oxide, Hormone Therapy, Postmenopausal Women

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleAccepts Healthy Volunteers

All volunteer subjects will be assessed for study participation, including a cardiovascular physical examination and resting electrocardiogram. Fasting blood will be taken for SMAC, CBC, thyroid battery, lipid levels, estradiol and FSH levels under screening protocol 94-H-0045. A urine pregnancy test will be performed in women with a uterus and cessation of menses less than 6 months. Aspirin and non-steroidal anti-inflammatory drugs and steroidal drugs (oral, ointment, drops or inhalation) will be stopped 10 days prior to starting the study and discontinued throughout the study. Thirty hypercholesterolemic (LDL greater than 130 mg/dL) postmenopausal women who have not taken estrogenic hormone, antioxidant vitamins (A, C, E), or lipid-lowering therapy in the preceding 2 months will be selected to take part in this double-blind, cross-over study. No subjects with plasma estradiol level greater than 50 pg/ml and FSH less than 50 pg/ml. No subjects with blood pressure greater than 160/100 mm/Hg (off medication). No subjects smoking cigarettes within 6 months. No pregnant subjects. No subjects with a history of deep venous thrombosis/pulmonary embolus. No subjects with important chronic medical conditions (cancer, coronary artery disease, diabetes mellitus, COPD, renal disease) other than hypothyroidism if the subject is euthyroid on thyroid replacement. No subjects who refuse to follow nitrate-restricted diet for 3 days prior to each study.

Sites / Locations

  • National Heart, Lung and Blood Institute (NHLBI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001752
Brief Title
Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women
Official Title
Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
August 1999
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

Brief Summary
Estrogen therapy has been associated with reduced risk of coronary heart disease events in observational studies of postmenopausal women. Although favorable effects of estrogen on lipoprotein cholesterol levels probably account for much of this benefit, direct vascular effects (vasomotor, hemostatic, anti-inflammatory) regulated by nitric oxide (NO) may also be of importance. We have recently shown that vasodilator effects of estrogen in the coronary circulation are due to enhanced bioactivity of NO released from the endothelium. Estrogen has been shown to stimulate synthesis and activity of the enzyme NO synthase with enhanced NO synthesis in endothelial cells in culture. Because L-arginine is the natural substrate for the enzyme NO synthase, we propose that the combination of L-arginine and estrogen might have additive vasomotor, hemostatic and anti-inflammatory effects in hypercholesterolemic postmenopausal women.
Detailed Description
Estrogen therapy has been associated with reduced risk of coronary heart disease events in observational studies of postmenopausal women. Although favorable effects of estrogen on lipoprotein cholesterol levels probably account for much of this benefit, direct vascular effects (vasomotor, hemostatic, anti-inflammatory) regulated by nitric oxide (NO) may also be of importance. We have recently shown that vasodilator effects of estrogen in the coronary circulation are due to enhanced bioactivity of NO released from the endothelium. Estrogen has been shown to stimulate synthesis and activity of the enzyme NO synthase with enhanced NO synthesis in endothelial cells in culture. Because L-arginine is the natural substrate for the enzyme NO synthase, we propose that the combination of L-arginine and estrogen might have additive vasomotor, hemostatic and anti-inflammatory effects in hypercholesterolemic postmenopausal women.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Postmenopause
Keywords
Adhesion Molecules, Endothelial Function, Inflammation, Lipoproteins, Nitric Oxide, Hormone Therapy, Postmenopausal Women

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
L-arginine
Intervention Type
Drug
Intervention Name(s)
Estrogen

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
All volunteer subjects will be assessed for study participation, including a cardiovascular physical examination and resting electrocardiogram. Fasting blood will be taken for SMAC, CBC, thyroid battery, lipid levels, estradiol and FSH levels under screening protocol 94-H-0045. A urine pregnancy test will be performed in women with a uterus and cessation of menses less than 6 months. Aspirin and non-steroidal anti-inflammatory drugs and steroidal drugs (oral, ointment, drops or inhalation) will be stopped 10 days prior to starting the study and discontinued throughout the study. Thirty hypercholesterolemic (LDL greater than 130 mg/dL) postmenopausal women who have not taken estrogenic hormone, antioxidant vitamins (A, C, E), or lipid-lowering therapy in the preceding 2 months will be selected to take part in this double-blind, cross-over study. No subjects with plasma estradiol level greater than 50 pg/ml and FSH less than 50 pg/ml. No subjects with blood pressure greater than 160/100 mm/Hg (off medication). No subjects smoking cigarettes within 6 months. No pregnant subjects. No subjects with a history of deep venous thrombosis/pulmonary embolus. No subjects with important chronic medical conditions (cancer, coronary artery disease, diabetes mellitus, COPD, renal disease) other than hypothyroidism if the subject is euthyroid on thyroid replacement. No subjects who refuse to follow nitrate-restricted diet for 3 days prior to each study.
Facility Information:
Facility Name
National Heart, Lung and Blood Institute (NHLBI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9386140
Citation
Guetta V, Quyyumi AA, Prasad A, Panza JA, Waclawiw M, Cannon RO 3rd. The role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women. Circulation. 1997 Nov 4;96(9):2795-801. doi: 10.1161/01.cir.96.9.2795.
Results Reference
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PubMed Identifier
1454805
Citation
Hayashi T, Fukuto JM, Ignarro LJ, Chaudhuri G. Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11259-63. doi: 10.1073/pnas.89.23.11259.
Results Reference
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Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women

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