Type 2 DiabetesNCT06016478
The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes
A study testing L-citrulline in people with Type 2 Diabetes, run by Texas Tech University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- L-citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2023to 1 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- < 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
TTU Kinesiology and Sport Management Building
Lubbock, Texas, 79409
About this study
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.
Read the 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.
- Conditions
- Type 2 Diabetes
- Being tested
- L-citrulline, Placebo
- Keywords
- Endothelial function, Arterial stiffness, Hyperglycemia, Oral glucose tolerance test, Aortic blood pressure, Blood glucose, Lean mass
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDietary 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.
PlaceboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| L-citrulline | Experimental | 6 grams/day Receives: Dietary Supplement: L-citrulline |
| Placebo | Placebo comparator | Microcrystalline cellulose Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 4 weeks
Secondary outcomes (6)
Change in body composition
Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.
Measured: 4 weeks
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.
Measured: 4 weeks
Change in insulin levels
Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.
Measured: 4 weeks
Change in serum arginine levels
Serum arginine levels will tested at baseline and after 4 weeks of supplementation.
Measured: 4 weeks
Change in serum arginase activity levels
Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.
Measured: 4 weeks
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start1 May 2023
- Primary completion1 Jul 2024
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind (subject, investigator), randomized, cross-over, placebo-controlled
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Texas Tech University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arturo Figueroa, Texas Tech University
- Investigators
- Arturo Figueroa, Ph.D, MD, Principal investigator, Texas Tech University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06016478
- Sponsor's protocol ID
- IRB2022-1056
- Status last verified
- Oct 2023
- First submitted
- 19 Aug 2023
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06016478
- Acronym / sponsor ID
- IRB2022-1056
- Conditions
- Type 2 Diabetes
- Keywords
- Endothelial function, Arterial stiffness, Hyperglycemia, Oral glucose tolerance test, Aortic blood pressure, Blood glucose, Lean mass
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Texas Tech UniversityUniversity, hospital or other
- Study start
- 1 May 2023 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind (subject, investigator), randomized, cross-over, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| L-citrulline | Experimental | Dietary Supplement: L-citrulline6 grams/day |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboMicrocrystalline cellulose |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- < 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-citrulline4 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. | Dietary supplement | L-citrulline |
| Placebo4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night. | Dietary supplement | Placebo |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
6 secondary outcomes
Change in body composition
Time frame: 4 weeks
Change in muscle strength
Time frame: 4 weeks
Change in insulin levels
Time frame: 4 weeks
Change in serum arginine levels
Time frame: 4 weeks
Change in serum arginase activity levels
Time frame: 4 weeks
Change in 24-hour ambulatory blood pressure monitoring
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arturo Figueroa, Ph.D, MD principal investigator
Texas Tech University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-citrulline in people with Type 2 Diabetes, run by Texas Tech University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in macrovascular endothelial function in the fasted condition (time frame: 4 weeks). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.