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

NCT06016478 | Completed

• 1 other identifier: IRB2022-1056
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Keywords

Endothelial function; Arterial stiffness; Hyperglycemia; Oral glucose tolerance test; Aortic blood pressure; Blood glucose; Lean mass

Outcome Measures

Primary Outcomes (15)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (6)

• Change in body composition

  4 weeks

• Change in muscle strength

  4 weeks

• Change in insulin levels

  4 weeks

• Change in serum arginine levels

  4 weeks

• Change in serum arginase activity levels

  4 weeks

Study Arms (2)

L-citrulline

EXPERIMENTAL

6 grams/day

Dietary Supplement: L-citrulline

Placebo

PLACEBO COMPARATOR

Microcrystalline cellulose

Dietary Supplement: Placebo

Interventions

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.

L-citrulline

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.

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \< 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

Sponsors & Collaborators

• Texas Tech University: lead

Study Sites (1)

TTU Kinesiology and Sport Management Building

Lubbock, Texas, 79409, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Arturo Figueroa, Ph.D, MD

  Texas Tech University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind (subject, investigator), randomized, cross-over, placebo-controlled
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Arturo Figueroa, Principal Investigator

Model Details: Double-blind (subject, investigator), randomized, cross-over, placebo-controlled

Study Record Dates

• First Submitted: August 19, 2023
• First Posted: August 29, 2023
• Study Start: May 1, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: May 15, 2025

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)