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

Primary Purpose

Type 2 Diabetes

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
L-citrulline
Placebo
Sponsored by
Texas Tech University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes focused on measuring Endothelial function, Arterial stiffness, Hyperglycemia, Oral glucose tolerance test, Aortic blood pressure, Blood glucose, Lean mass

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • TTU Kinesiology and Sport Management BuildingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

L-citrulline

Placebo

Arm Description

6 grams/day

Microcrystalline cellulose

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

Change in body composition
Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.
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.
Change in insulin levels
Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.
Change in serum arginine levels
Serum arginine levels will tested at baseline and after 4 weeks of supplementation.
Change in serum arginase activity levels
Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.
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.

Full Information

First Posted
August 19, 2023
Last Updated
October 10, 2023
Sponsor
Texas Tech University
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1. Study Identification

Unique Protocol Identification Number
NCT06016478
Brief Title
The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes
Official Title
The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas Tech University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Endothelial function, Arterial stiffness, Hyperglycemia, Oral glucose tolerance test, Aortic blood pressure, Blood glucose, Lean mass

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Double-blind (subject, investigator), randomized, cross-over, placebo-controlled
Masking
ParticipantInvestigator
Masking Description
Double-blind (subject, investigator), randomized, cross-over, placebo-controlled
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-citrulline
Arm Type
Experimental
Arm Description
6 grams/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Microcrystalline cellulose
Intervention Type
Dietary Supplement
Intervention Name(s)
L-citrulline
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
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 Outcome Measure Information:
Title
Change in macrovascular endothelial function in the fasted condition
Description
Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in macrovascular endothelial function during acute hyperglycemia
Description
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.
Time Frame
4 weeks
Title
Change in microvascular endothelial function in the fasted condition
Description
Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in microvascular endothelial function in the fasted condition
Description
Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in microvascular endothelial function during acute hyperglycemia
Description
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.
Time Frame
4 weeks
Title
Change in blood glucose levels in the fasted condition
Description
Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in blood glucose levels during acute hyperglycemia
Description
Blood glucose levels will be measured by finger prick at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in central and peripheral arterial stiffness in the fasted condition
Description
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.
Time Frame
4 weeks
Title
Change in central and peripheral arterial stiffness during acute hyperglycemia
Description
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.
Time Frame
4 weeks
Title
Change in blood pressure in the fasted condition
Description
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.
Time Frame
4 weeks
Title
Change in blood pressure during acute hyperglycemia
Description
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.
Time Frame
4 weeks
Title
Change in stroke volume in the fasted condition
Description
Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in stroke volume during acute hyperglycemia
Description
Stroke volume will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in total peripheral resistance in the fasted condition
Description
Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in total peripheral resistance during acute hyperglycemia
Description
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.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Change in body composition
Description
Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in muscle strength
Description
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.
Time Frame
4 weeks
Title
Change in insulin levels
Description
Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in serum arginine levels
Description
Serum arginine levels will tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in serum arginase activity levels
Description
Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Change in 24-hour ambulatory blood pressure monitoring
Description
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.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arturo Figueroa, Ph.D, MD
Phone
806-834-5587
Email
arturo.figueroa@ttu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arturo Figueroa, Ph.D, MD
Organizational Affiliation
Texas Tech University
Official's Role
Principal Investigator
Facility Information:
Facility Name
TTU Kinesiology and Sport Management Building
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79409
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arturo Figueroa, M.D., Ph.D.
Phone
806-834-5587
Email
arturo.figueroa@ttu.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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