MenopauseNCT06025383
2 Weeks of Citrulline Supplementation on Arterial Function in Postmenopausal Women With Elevated Blood Pressure or Hypertension
A study testing L-Citrulline in people with Menopause and Hypertension, run by Texas Tech University at 1 site in United States.
Trial summary
The objective of this project is to elucidate the effect of L-Citrulline (L-CIT) supplementation on vascular function at rest and during rhythmic handgrip exercise and functional sympatholysis via lower-body negative pressure in postmenopausal women with elevated blood pressure and hypertension. Read more about this study
- Who is it for?
- Ages 50 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause, Hypertension
- 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
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 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 50 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal women (defined as the absence of menstruation for at least 1 year).
- Resting systolic blood pressure 120-150 mmHg.
- Between the ages of 50 - 70 years.
- Sedentary (< 120 minutes of exercise/week).
- Body mass index of 25 - 39.9 kg/m2.
- Fasting glucose < 126 mg/dL and HbA1c < 6.5%.
Who cannot join
- Body mass index ≥ 40 or < 25 kg/m2.
- Systolic blood pressure > 150 mmHg.
- Taking more than two antihypertensive medications.
- Cardiovascular diseases, type I/II diabetes, musculoskeletal disorders, or cancer.
- Changes in hypertensive medication in the past three months.
- Began or changed hormone replacement therapy in the past 6 months.
Show all 10Show fewer
- Current smoker.
- Heavy drinking (> 7 alcoholic drinks/week).
- Participants on beta-blockers or other vasodilatory supplements (nitrates).
- Incorporated in a weight loss program and/or aerobic or resistance training program.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 2 Weeks of L-Citrulline Supplementation Improves Arterial Function and Systolic Blood Pressure at Rest and During Exercise in Postmenopausal Women With Elevated Blood Pressure and Hypertension
The objective of this project is to elucidate the effect of L-Citrulline (L-CIT) supplementation on vascular function at rest and during rhythmic handgrip exercise and functional sympatholysis via lower-body negative pressure in postmenopausal women with elevated blood pressure and hypertension.
Read the detailed description
Using a double-blind, randomized, placebo-controlled, and crossover design, overweight or obese postmenopausal women with elevated blood pressure (BP) or hypertension will receive CIT (6 grams/day) or placebo for 2 weeks, separated by a two-week washout period.
There will be a total of 5 laboratory visits. The 1st visit will take approximately 1 hour. The 2nd - 5th visits will take about 2 hours and 15 minutes. Visit 1 will be a screening visit, visits 2 and 4 will be considered baseline visits, and visits 3 and 5 will be following the participants' two weeks of supplementation. Arterial stiffness (carotid-femoral and femoral-dorsalis pedis pulse wave velocity) and endothelial function will be assessed at rest. Additionally, brachial artery blood flow, forearm muscle oxygenation, cardiovascular hemodynamics (stroke volume, cardiac output, systemic vascular resistance), and BP will be assessed at rest, during 6 minutes of rhythmic handgrip exercise at 30% of a predetermined maximal voluntary contraction, and 2 minutes of superimposed lower body negative pressure to increase sympathetic activity.
- Conditions
- Menopause, Hypertension
- Being tested
- L-Citrulline, Placebo
- Keywords
- Endothelial function, Blood flow, Blood pressure, Functional sympatholysis
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-CitrullineDietary supplement
2 weeks of L-Citrulline supplementation (6 grams/day)
PlaceboDietary supplement
2 weeks of microcrystalline cellulose supplementation (8 capsules/day)
| Study group | Role | What they receive |
|---|---|---|
| L-Citrulline | Experimental | L-Citrulline: 6 grams/day divided in 2 equal doses Receives: Dietary Supplement: L-Citrulline |
| Placebo | Placebo comparator | Microcrystalline cellulose: 8 capsules/day divided into 2 equal doses Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrovascular endothelial function at rest
Endothelial function will be assessed via brachial artery flow-mediated vasodilation (ultrasonography) during reactive hyperemia at baseline and after 2 weeks of each supplementation.
Measured: 2 weeks of each intervention
Microvascular endothelial function at rest
Endothelial function will be assessed via peripheral arterial tonometry (endoPAT) during reactive hyperemia at baseline and after 2 weeks of each supplementation.
Measured: 2 weeks of each intervention
Microvascular endothelial function at rest
Endothelial function will be assessed using forearm muscle oxygen saturation (near-infrared spectroscopy) during reactive hyperemia before and after 2 weeks of each supplementation.
Measured: 2 weeks of each intervention
Brachial artery blood flow at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Blood flow will be measured via Doppler ultrasound before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Forearm muscle oxygenation at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Muscle oxygen saturation will be measured via near-infrared spectroscopy before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Secondary outcomes (11)
Beat-to-beat blood pressure at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Blood pressure will be measured via a finger cuff (finometer) before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Aortic hemodynamics at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Aortic blood pressure and pressure waves will be assessed using radial applanation tonometry before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Stroke volume at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Stroke volume will be assessed via impedance cardiography before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Heart rate at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Heart rate will be assessed via impedance cardiography before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Systemic vascular resistance at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Systemic vascular resistance will be assessed via impedance cardiography before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Central and peripheral arterial stiffness at rest
Carotid-femoral and femoral-dorsalis pedis pulse wave velocity will be measured using arterial applanation tonometry before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Forearm muscle strength
Maximal forearm muscle strength will be measured using a handgrip dynamometer before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
L-arginine levels
Serum levels of l-arginine will be assessed before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Nitric oxide levels
Serum levels of nitric oxide will be assessed before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
L-citrulline levels
Serum levels of l-citrulline will be assessed before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
L-ornithine levels
Serum levels of l-ornithine will be assessed before and after 2 weeks of each intervention.
Measured: 2 weeks of each intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2023
- Study start20 Jul 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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies 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
- Cross-Over Assignment Double (Participant, Investigator) randomized, double-blind, placebo-controlled, cross-over study design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 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, Principal investigator, Texas Tech University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06025383
- Sponsor's protocol ID
- IRB2022-1055
- Status last verified
- Aug 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
Publications
Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women. Med Sci Sports Exerc. 2022 May 1;54(5):761-768. doi: 10.1249/MSS.0000000000002848. Epub 2022 Jan 3.
PubMed 34974502Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients. 2022 Oct 20;14(20):4396. doi: 10.3390/nu14204396.
PubMed 36297080Kang Y, Dillon KN, Martinez MA, Maharaj A, Fischer SM, Figueroa A. Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women. Nutrients. 2022 Dec 23;15(1):74. doi: 10.3390/nu15010074.
PubMed 36615732Figueroa A, Maharaj A, Kang Y, Dillon KN, Martinez MA, Morita M, Nogimura D, Fischer SM. Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women. Nutrients. 2023 Mar 23;15(7):1557. doi: 10.3390/nu15071557.
PubMed 37049398Figueroa A, Alvarez-Alvarado S, Jaime SJ, Kalfon R. l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men. Br J Nutr. 2016 Jul;116(2):279-85. doi: 10.1017/S0007114516001811. Epub 2016 May 10.
PubMed 27160957
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
- 2 Weeks of L-Citrulline Supplementation Improves Arterial Function and Systolic Blood Pressure at Rest and During Exercise in Postmenopausal Women With Elevated Blood Pressure and Hypertension
- ClinicalTrials.gov ID
- NCT06025383
- Acronym / sponsor ID
- IRB2022-1055
- Conditions
- Menopause, Hypertension
- Keywords
- Endothelial function, Blood flow, Blood pressure, Functional sympatholysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Texas Tech UniversityUniversity, hospital or other
- Study start
- 20 Jul 2023 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 6 Sep 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 objective of this project is to elucidate the effect of L-Citrulline (L-CIT) supplementation on vascular function at rest and during rhythmic handgrip exercise and functional sympatholysis via lower-body negative pressure in postmenopausal women with elevated blood pressure and hypertension.
Detailed description
Using a double-blind, randomized, placebo-controlled, and crossover design, overweight or obese postmenopausal women with elevated blood pressure (BP) or hypertension will receive CIT (6 grams/day) or placebo for 2 weeks, separated by a two-week washout period.
There will be a total of 5 laboratory visits. The 1st visit will take approximately 1 hour. The 2nd - 5th visits will take about 2 hours and 15 minutes. Visit 1 will be a screening visit, visits 2 and 4 will be considered baseline visits, and visits 3 and 5 will be following the participants' two weeks of supplementation. Arterial stiffness (carotid-femoral and femoral-dorsalis pedis pulse wave velocity) and endothelial function will be assessed at rest. Additionally, brachial artery blood flow, forearm muscle oxygenation, cardiovascular hemodynamics (stroke volume, cardiac output, systemic vascular resistance), and BP will be assessed at rest, during 6 minutes of rhythmic handgrip exercise at 30% of a predetermined maximal voluntary contraction, and 2 minutes of superimposed lower body negative pressure to increase sympathetic activity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Cross-Over Assignment Double (Participant, Investigator) randomized, double-blind, placebo-controlled, cross-over study design
| Arm | Type | Receives |
|---|---|---|
| L-Citrulline | Experimental | Dietary Supplement: L-CitrullineL-Citrulline: 6 grams/day divided in 2 equal doses |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboMicrocrystalline cellulose: 8 capsules/day divided into 2 equal doses |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Postmenopausal women (defined as the absence of menstruation for at least 1 year).
- Resting systolic blood pressure 120-150 mmHg.
- Between the ages of 50 - 70 years.
- Sedentary (< 120 minutes of exercise/week).
- Body mass index of 25 - 39.9 kg/m2.
Key exclusion criteria (10 listed)
- Body mass index ≥ 40 or < 25 kg/m2.
- Systolic blood pressure > 150 mmHg.
- Taking more than two antihypertensive medications.
- Cardiovascular diseases, type I/II diabetes, musculoskeletal disorders, or cancer.
- Changes in hypertensive medication in the past three 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-Citrulline2 weeks of L-Citrulline supplementation (6 grams/day) | Dietary supplement | L-Citrulline |
| Placebo2 weeks of microcrystalline cellulose supplementation (8 capsules/day) | Dietary supplement | Placebo |
Primary outcome
Macrovascular endothelial function at rest
Time frame: 2 weeks of each intervention
Endothelial function will be assessed via brachial artery flow-mediated vasodilation (ultrasonography) during reactive hyperemia at baseline and after 2 weeks of each supplementation.
Microvascular endothelial function at rest
Time frame: 2 weeks of each intervention
Endothelial function will be assessed via peripheral arterial tonometry (endoPAT) during reactive hyperemia at baseline and after 2 weeks of each supplementation.
Microvascular endothelial function at rest
Time frame: 2 weeks of each intervention
Endothelial function will be assessed using forearm muscle oxygen saturation (near-infrared spectroscopy) during reactive hyperemia before and after 2 weeks of each supplementation.
Brachial artery blood flow at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Time frame: 2 weeks of each intervention
Blood flow will be measured via Doppler ultrasound before and after 2 weeks of each intervention.
Forearm muscle oxygenation at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Time frame: 2 weeks of each intervention
Muscle oxygen saturation will be measured via near-infrared spectroscopy before and after 2 weeks of each intervention.
11 secondary outcomes
Beat-to-beat blood pressure at rest and during rhythmic handgrip exercise with and without lower-body negative pressure
Time frame: 2 weeks of each intervention
Aortic hemodynamics at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Time frame: 2 weeks of each intervention
Stroke volume at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Time frame: 2 weeks of each intervention
Heart rate at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Time frame: 2 weeks of each intervention
Systemic vascular resistance at rest and during rhythmic handgrip exercise with and without lower body negative pressure
Time frame: 2 weeks of each intervention
Central and peripheral arterial stiffness at rest
Time frame: 2 weeks of each intervention
Forearm muscle strength
Time frame: 2 weeks of each intervention
L-arginine levels
Time frame: 2 weeks of each intervention
Nitric oxide levels
Time frame: 2 weeks of each intervention
L-citrulline levels
Time frame: 2 weeks of each intervention
L-ornithine levels
Time frame: 2 weeks of each intervention
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.
- Background: PubMed 34974502Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women. Med Sci Sports Exerc. 2022 May 1;54(5):761-768. doi: 10.1249/MSS.0000000000002848. Epub 2022 Jan 3.
- Background: PubMed 36297080Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients. 2022 Oct 20;14(20):4396. doi: 10.3390/nu14204396.
- Background: PubMed 36615732Kang Y, Dillon KN, Martinez MA, Maharaj A, Fischer SM, Figueroa A. Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women. Nutrients. 2022 Dec 23;15(1):74. doi: 10.3390/nu15010074.
- Background: PubMed 37049398Figueroa A, Maharaj A, Kang Y, Dillon KN, Martinez MA, Morita M, Nogimura D, Fischer SM. Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women. Nutrients. 2023 Mar 23;15(7):1557. doi: 10.3390/nu15071557.
- Background: PubMed 27160957Figueroa A, Alvarez-Alvarado S, Jaime SJ, Kalfon R. l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men. Br J Nutr. 2016 Jul;116(2):279-85. doi: 10.1017/S0007114516001811. Epub 2016 May 10.
- 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 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 Menopause and Hypertension, 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 6 inclusion and 10 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?
Macrovascular endothelial function at rest (time frame: 2 weeks of each intervention). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06025383, which also lists 5 linked publications.
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.