Effects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome

Sponsor

Texas Tech University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06025357

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this project is to provide evidence that L-Citrulline (CIT) supplementation can improve vascular function in the fasted and acute hyperglycemia conditions in middle-aged and older women with metabolic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome Menopause	Dietary Supplement: L-Citrulline supplementation Dietary Supplement: Placebo	N/A

Detailed Description

Using a double-blind, randomized, placebo-controlled, and parallel design, middle-aged and older women with metabolic syndrome will be randomized into receiving either CIT supplementation (10g/day) or placebo (Microcrystalline Cellulose) for 4 weeks.

The first visit will be approximately 1hr and 30 minutes. The 2nd and 3rd visits will each be approximately 2hrs and 30 minutes, separated by 4 weeks in between each visit. During visits 2 and 3, vascular measurements will be assessed in the fasted state and 30, 60, and 90 minutes after acute glucose ingestion (75g).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel Assignment Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study designParallel Assignment Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study design

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Effects of L-Citrulline Supplementation on Vascular Function During Fasted and Acute Hyperglycemia in Middle-aged and Older Women With Metabolic Syndrome

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-citrulline L-citrulline: 10 grams/day	Dietary Supplement: L-Citrulline supplementation 4 weeks of L-Citrulline supplementation (10 grams/day).
Experimental: Placebo Microcrystalline Cellulose	Dietary Supplement: Placebo 4 weeks of microcrystalline Cellulose supplementation.

Arm

Intervention/Treatment

Experimental: L-citrulline

L-citrulline: 10 grams/day

Dietary Supplement: L-Citrulline supplementation

4 weeks of L-Citrulline supplementation (10 grams/day).

Experimental: Placebo

Microcrystalline Cellulose

Dietary Supplement: Placebo

4 weeks of microcrystalline Cellulose supplementation.

Outcome Measures

Primary Outcome Measures

Macrovascular Endothelial function in the fasted condition [4 weeks]
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Microvascular endothelial function in the fasted condition [4 weeks]
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) will assessed during reactive hyperemia at baseline and after 4 weeks of supplementation.
Microvascular digital endothelial function in the fasted condition [4 weeks]
Endothelial function will be measured using peripheral (finger) arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Macrovascular Endothelial function during acute hyperglycemia [4 weeks]
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Microvascular forearm endothelial function during acute hyperglycemia [4 weeks]
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Central and peripheral arterial stiffness in the fasted condition [4 weeks]
Arterial stiffness will be measured using central (carotid-femoral) and peripheral (femoral-ankle) PWV at baseline and after 4 weeks of supplementation.
Central arterial stiffness during acute hyperglycemia [4 weeks]
Arterial stiffness will be measured using central (carotid-femoral) PWV at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Blood pressure in the fasted condition [4 weeks]
Brachial and aortic blood pressures will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.
Blood pressure during acute hyperglycemia [4 weeks]
Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured after an oral glucose ingestion at 30, 60, and 90 minutes at baseline and after 4 weeks of supplementation.
Total peripheral resistance in the fasted condition. [4 weeks]
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Total peripheral resistance during acute hyperglycemia [4 weeks]
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Stroke volume in the fasted condition [4 weeks]
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Stroke volume during acute hyperglycemia [4 weeks]
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
24-hour ambulatory blood pressure monitoring [4 weeks]
An ambulatory blood pressure cuff, measuring blood pressure for 24-hours will be obtained on two separate days at baseline and after 4 weeks of supplementation.

Secondary Outcome Measures

Serum glucose and insulin levels. [4 weeks]
Serum glucose and insulin levels will be tested at baseline and after 4 weeks of supplementation.
Serum arginine levels [4 weeks]
Serum L-Arginine levels will be tested at baseline and after 4 weeks of supplementation.
Serum arginase levels [4 weeks]
Serum arginase levels will be tested at baseline and after 4 weeks of supplementation.
Serum Nitric Oxide levels [4 weeks]
Serum nitric oxide levels will be tested at baseline and after 4 weeks of supplementation.
Serum Endothelin-1 levels [4 weeks]
Serum endothelin-1 levels will be tested at baseline and after 4 weeks of supplementation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 79 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Must present at least 3 of the following 5 cardiometabolic risk factors

Waist circumference ≥88 cm
Fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4%.
Blood pressure ≥130 mm Hg
Triglyceride ≥ 150 mg/dL
HDL <50 mg/dL

The following are also inclusion criteria's:

Women aged 45-79 years old
Body mass index ≤ 39.9 kg/m2
Sedentary (defined as < 120 min/week of exercise)
Abstain from any dietary supplements with vascular effects for one month prior to the beginning of the study and until participation in study has terminated.

Exclusion Criteria:

< 45 and > 79 years of age
Use of medications and/or any supplements that may affect outcome variables (such as arginine-containing supplements, nitroglycerin, statin drugs, biguanides, insulin, beta blockers, statins, verapamil)
Systolic blood pressure ≥ 160 mmHg
BMI > 40 kg/m2
Recent changes in medication (3 months)
Current smoking any tobacco use
Cardiovascular disease, diabetes (Type 1 or 2), and other metabolic or chronic diseases
More than 7 alcoholic drinks/week of consumption