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

Metabolic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06025357
• Other study ID #: IRB2022-362
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: August 1, 2024

Study information

• Verified date: August 2023
• Source: Texas Tech University
• Contact: Arturo Figueroa, Ph.D,MD
• Phone: 806-834-5587
• Email: arturo.figueroa[@]ttu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause
• Metabolic Syndrome
• Syndrome

Intervention

Dietary Supplement:
• L-Citrulline supplementation
4 weeks of L-Citrulline supplementation (10 grams/day).
• Placebo
4 weeks of microcrystalline Cellulose supplementation.

Locations

Country	Name	City	State
United States	TTU Kinesiology and Sport Management Building	Lubbock	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Texas Tech University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Figueroa A, Alvarez-Alvarado S, Ormsbee MJ, Madzima TA, Campbell JC, Wong A. Impact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp Gerontol. 2015 Mar;63:35-40. doi: 10.1016/j.exger.2015.01.046. Epub 2015 Jan 28. — View Citation

Figueroa A, Maharaj A, Kang Y, Dillon KN, Martinez MA, Morita M, Nogimura D, Fischer SM. Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women. Nutrients. 2023 Mar 23;15(7):1557. doi: 10.3390/nu15071557. — View Citation

Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women. Med Sci Sports Exerc. 2022 May 1;54(5):761-768. doi: 10.1249/MSS.0000000000002848. Epub 2022 Jan 3. — View Citation

Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients. 2022 Oct 20;14(20):4396. doi: 10.3390/nu14204396. — View Citation

McDonald JD, Mah E, Chitchumroonchokchai C, Dey P, Labyk AN, Villamena FA, Volek JS, Bruno RS. Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem. 2019 Jan;63:165-176. doi: 10.1016/j.jnutbio.2018.09.018. Epub 2018 Sep 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Macrovascular Endothelial function in the fasted condition	Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Microvascular endothelial function in the fasted condition	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.	4 weeks
Primary	Microvascular digital endothelial function in the fasted condition	Endothelial function will be measured using peripheral (finger) arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Macrovascular Endothelial function during acute hyperglycemia	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.	4 weeks
Primary	Microvascular forearm endothelial function during acute hyperglycemia	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.	4 weeks
Primary	Central and peripheral arterial stiffness in the fasted condition	Arterial stiffness will be measured using central (carotid-femoral) and peripheral (femoral-ankle) PWV at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Central arterial stiffness during acute hyperglycemia	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.	4 weeks
Primary	Blood pressure in the fasted condition	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.	4 weeks
Primary	Blood pressure during acute hyperglycemia	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.	4 weeks
Primary	Total peripheral resistance in the fasted condition.	Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Total peripheral resistance during acute hyperglycemia	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.	4 weeks
Primary	Stroke volume in the fasted condition	Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Stroke volume during acute hyperglycemia	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.	4 weeks
Primary	24-hour ambulatory blood pressure monitoring	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.	4 weeks
Secondary	Serum glucose and insulin levels.	Serum glucose and insulin levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Serum arginine levels	Serum L-Arginine levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Serum arginase levels	Serum arginase levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Serum Nitric Oxide levels	Serum nitric oxide levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Serum Endothelin-1 levels	Serum endothelin-1 levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks