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Completed

NCT Number: NCT06016478

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

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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Hyperglycemia Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

TTU Kinesiology and Sport Management Building

Lubbock, Texas, 79409, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

L-citrulline

Dietary Supplement

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

Dietary Supplement

4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.

Primary outcomes

  1. Change in macrovascular endothelial function in the fasted condition

    Time frame: 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.

  2. Change in macrovascular endothelial function during acute hyperglycemia

    Time frame: 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.

  3. Change in microvascular endothelial function in the fasted condition

    Time frame: 4 weeks

    Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.

  4. Change in microvascular endothelial function in the fasted condition

    Time frame: 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.

  5. Change in microvascular endothelial function during acute hyperglycemia

    Time frame: 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.

  6. Change in blood glucose levels in the fasted condition

    Time frame: 4 weeks

    Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.

  7. Change in blood glucose levels during acute hyperglycemia

    Time frame: 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.

  8. Change in central and peripheral arterial stiffness in the fasted condition

    Time frame: 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.

  9. Change in central and peripheral arterial stiffness during acute hyperglycemia

    Time frame: 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.

  10. Change in blood pressure in the fasted condition

    Time frame: 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.

  11. Change in blood pressure during acute hyperglycemia

    Time frame: 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.

  12. Change in stroke volume in the fasted condition

    Time frame: 4 weeks

    Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.

  13. Change in stroke volume during acute hyperglycemia

    Time frame: 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.

  14. Change in total peripheral resistance in the fasted condition

    Time frame: 4 weeks

    Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.

  15. Change in total peripheral resistance during acute hyperglycemia

    Time frame: 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.

Secondary outcomes

  1. Change in body composition

    Time frame: 4 weeks

    Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.

  2. Change in muscle strength

    Time frame: 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.

  3. Change in insulin levels

    Time frame: 4 weeks

    Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.

  4. Change in serum arginine levels

    Time frame: 4 weeks

    Serum arginine levels will tested at baseline and after 4 weeks of supplementation.

  5. Change in serum arginase activity levels

    Time frame: 4 weeks

    Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.

  6. Change in 24-hour ambulatory blood pressure monitoring

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Texas Tech University

Other

Registry information

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Aug 29, 2023
Registry last updated
May 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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