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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06016478
• Other study ID #: IRB2022-1056
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: July 2024

Study information

• Verified date: October 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Dietary Supplement:
• L-citrulline
4 weeks of L-citrulline (6 g/day) in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.
• Placebo
4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in macrovascular endothelial function in the fasted condition	Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in macrovascular endothelial function during acute hyperglycemia	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.	4 weeks
Primary	Change in microvascular endothelial function in the fasted condition	Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in microvascular endothelial function in the fasted condition	Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in microvascular endothelial function during acute hyperglycemia	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.	4 weeks
Primary	Change in blood glucose levels in the fasted condition	Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in blood glucose levels during acute hyperglycemia	Blood glucose levels will be measured by finger prick at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in central and peripheral arterial stiffness in the fasted condition	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.	4 weeks
Primary	Change in central and peripheral arterial stiffness during acute hyperglycemia	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.	4 weeks
Primary	Change in blood pressure in the fasted condition	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.	4 weeks
Primary	Change in blood pressure during acute hyperglycemia	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.	4 weeks
Primary	Change in stroke volume in the fasted condition	Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in stroke volume during acute hyperglycemia	Stroke volume will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in total peripheral resistance in the fasted condition	Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.	4 weeks
Primary	Change in total peripheral resistance during acute hyperglycemia	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.	4 weeks
Secondary	Change in body composition	Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Change in muscle strength	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.	4 weeks
Secondary	Change in insulin levels	Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Change in serum arginine levels	Serum arginine levels will tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Change in serum arginase activity levels	Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.	4 weeks
Secondary	Change in 24-hour ambulatory blood pressure monitoring	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.	4 weeks