The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes

Not Applicable

Completed

• Conditions: Type 2 Diabetes
• Interventions: Dietary Supplement: L-citrulline; Dietary Supplement: Placebo

• Registration Number: NCT06016478
• Lead Sponsor: Texas Tech University

Brief Summary

The purpose of this study is to examine the effect of 4 weeks of Citrulline supplementation on macro- and microvascular function during acute hyperglycemia in middle-aged and older adults with type 2 diabetes.

Detailed Description

Using a double-blind, randomized, placebo-controlled, and cross-over design, middle-aged and older adults with type 2 diabetes will be randomized to receive either CIT supplementation (6g/day) or placebo (Microcrystalline Cellulose, 6g/day) for 4 weeks.

There will be a total of 5 laboratory visits. Visit 1 (screening visit) will take approximately 1 hour and 30 minutes, visit 2 will take approximately 2 hours and 30 minutes, and visits 3-5 will be approximately 3 hours each.

Visit 1 will measure blood pressure, blood glucose and lipid levels, anthropometry, body composition, and muscle strengths. Visits 2-5 will assess vascular function and glucose control during fasted and acute hyperglycemia conditions induced by 75g of glucose ingestion.

Study Timeline

• Study Start: 2023-05-01
• Study First Submitted: 2023-08-19
• Study First Submitted QC: 2023-08-24
• Study First Posted: 2023-08-29
• Status Verified: 2023-10
• Primary Completion: 2024-07-01
• Study Completion: 2024-07-01
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Middle-aged and older women and men between 40-75 years old
• A physician diagnosed type 2 diabetes at least 3 months ago
• Treated with an oral hypoglycemic medication
• Body mass index < 40 kg/m2
• Systolic blood pressure < 160 mmHg
• Sedentary (defined as < 120 min/week of exercise)
• Not currently participating in exercise or dietary interventions for at least 2 months prior the present study and willing to abstain from participating in those strategies during the duration of this study.

Exclusion Criteria

• < 40 years of age and > 65 years of age
• Use of medications and/or any supplements that may affect outcome variables (such as arginine- or citrulline-containing supplements, nitrates, and nitroglycerin)
• Body mass index ≥ 40 kg/m2
• Systolic blood pressure ≥ 160 mmHg
• Recent changes in medications within 3 months
• Current smoking any tobacco use
• Type 1 diabetes, severe cardiovascular/renal/pulmonary diseases
• More than 7 alcoholic drinks/week of consumption
• Premenopausal women with an irregular menstrual cycle (oligomenorrhea) or pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
L-citrulline	L-citrulline	6 grams/day
Placebo	Placebo	Microcrystalline cellulose

Primary Outcome Measures

Name	Time	Method
Change in blood glucose levels in the fasted condition	4 weeks	Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.
Change in central and peripheral arterial stiffness in the fasted condition	4 weeks	Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at baseline and after 4 weeks of supplementation.
Change in blood pressure during acute hyperglycemia	4 weeks	Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in macrovascular endothelial function in the fasted condition	4 weeks	Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Change in blood glucose levels during acute hyperglycemia	4 weeks	Blood glucose levels will be measured by finger prick at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in central and peripheral arterial stiffness during acute hyperglycemia	4 weeks	Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in stroke volume in the fasted condition	4 weeks	Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.
Change in macrovascular endothelial function during acute hyperglycemia	4 weeks	Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in microvascular endothelial function in the fasted condition	4 weeks	Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Change in microvascular endothelial function during acute hyperglycemia	4 weeks	Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in blood pressure in the fasted condition	4 weeks	Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.
Change in stroke volume during acute hyperglycemia	4 weeks	Stroke volume will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in total peripheral resistance during acute hyperglycemia	4 weeks	Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Change in total peripheral resistance in the fasted condition	4 weeks	Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.

Secondary Outcome Measures

Name	Time	Method
Change in insulin levels	4 weeks	Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.
Change in serum arginine levels	4 weeks	Serum arginine levels will tested at baseline and after 4 weeks of supplementation.
Change in serum arginase activity levels	4 weeks	Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.
Change in 24-hour ambulatory blood pressure monitoring	4 weeks	Ambulatory blood pressure will be obtained using a monitor during daytime and nighttime on two separate days at baseline and after 4 weeks of supplementation.
Change in body composition	4 weeks	Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.
Change in muscle strength	4 weeks	Maximal handgrip strength will be measured using handgrip dynamometer. Leg extension and plantar flexion strength will be measured using the 10RM test at baseline and after 4 weeks of supplementation.

Trial Locations

Locations (1)

TTU Kinesiology and Sport Management Building; 🇺🇸 Lubbock, Texas, United States