HypertensionPhase 1/2NCT01185041
Watermelon Supplementation and Arterial Stiffness
A Phase 1/2 study testing Watermelon Extract in people with Hypertension, run by Florida State University at 1 site in United States.
Trial summary
Increased abdominal obesity (waist circumference) and systolic blood pressure (BP) are main risk factors for the metabolic syndrome. Approximately 60% of adults in the United States are prehypertensive or hypertensive. Read more about this study
- Who is it for?
- Ages 45 to 70 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Watermelon Extract
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Aug 2011
- Phase
- Phase 1/2
- 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 45 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Thirty men and women 45-70 years of age
- BP between 120-159/80-99 mmHg
- Waist circumference >102 cm in men and > 80 cm in women
Who cannot join
- BP >160/100 mmHg
- Asthma
- Glaucoma
- Herpes simplex
- Uncontrolled diabetes
- Neurological disease
Show all 18Show fewer
- Cardiovascular disease
- Inflammatory disease
- Kidney disease
- Hormone replacement therapy (HRT)
- Amino acid/vitamin supplementation\
- Corticosteroids or non-steroidal anti-inflammatory drugs
- Any drug known to affect BP or heart rate
- Glycemic control drugs
- Lipids reducing drugs
- Participants should not consume > 12 alcoholic drink/week
- Smokers
- Regular Exercisers (= 1.5 hour/week).
Trial locations and contacts
1 site in 1 country.
United States1 site
Cardiovascular Physiology Laboratory
Tallahassee, Florida, 32306
About this study
Official title: Effects of Oral L-citrulline/L-arginine in Watermelon on Central Blood Pressure and Arterial Stiffness in Individuals With Obesity-related High Blood Pressure
Increased abdominal obesity (waist circumference) and systolic blood pressure (BP) are main risk factors for the metabolic syndrome. Approximately 60% of adults in the United States are prehypertensive or hypertensive. Hypertension has been associated with abnormal endothelial and autonomic function, the two main mechanisms of BP regulation. Endothelial dysfunction, as a result of reduced NO (a vasodilator), and increased sympathetic nervous system activity contribute to arterial stiffness by enhancing the vasomotor tone. Because BP variations are sensed by baroreceptors in the wall of large arteries, increased stiffness of arteries may attenuate the control of BP by the autonomic nervous system leading to hypertension. High production of proinflammatory cytokines and low adiponectin (vascular protective molecule), are considered the underlying mechanisms leading to endothelial dysfunction and arterial stiffness. The recommended intervention for controlling BP in overweight/obese individuals with pre- and stage 1- hypertension is lifestyle modifications and not drug therapy. Among the dietary regimens that are reported to reduce BP is L-arginine, the substrate for endothelial NO production. Recently, oral L-citrulline has been shown to be more effective than L-arginine in improving circulating NO levels because is not affected by enzymatic degradation. Watermelon, the leading US melon crop, is one of the few natural foods rich in L-citrulline which is efficiently transformed to arginine in humans. The investigators long-term goal is to provide feasible and effective dietary ways to reduce cardiovascular risk factors in individuals with high abdominal fat and BP. The overall objective of this study is to bring forth evidence that watermelon supplementation will reduce BP and cardiovascular risk factors such as arterial stiffness, autonomic dysfunction and endothelial dysfunction. The investigators postulate that watermelon supplementation will reduce BP and arterial stiffness by enhancing endothelial function and reducing vascular inflammation. The findings of this study will provide a foundation for disseminating feasible, safe approaches for preventing and combating obesity-related hypertension at its early stage which does not require drug therapy.
Read the detailed description
The purpose of the study is to examine the effect of 12 weeks of L-citrulline/L-arginine in the form of watermelon supplementation on arterial function and autonomic neural control of the heart rate and blood pressure in older overweight/obese men and women with pre- and stage 1- hypertension. The specific aims of the study are:
- To investigate the extent to which daily consumption of watermelon supplementation containing L-citrulline/L-arginine (4/2 g) will reduce BP and arterial stiffness. This aim will examine the working hypothesis that watermelon supplementation will reduce BP and improve arterial function. This aim will be tested by measuring brachial and central (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and cold pressor test), and by evaluating arterial stiffness using pulse wave velocity of the aorta and legs as primary variables.
- To determine the effect of watermelon supplementation on endothelial function. There is evidence that watermelon improves endothelial function in rats. Hence, we postulate that watermelon in part exerts its vascular protective effects by modulating indices of endothelial function. This aim will be tested by measuring flow-mediated dilation using vascular ultrasound and circulating levels of vasodilators, vasoconstrictors, and markers of vascular inflammation (adiponectin, leptin, endothelin-1, angiotensin II, prostaglandin F2α, sVCAM-1, sICAM-1, and 8-isoprostane).
- To determine whether watermelon supplementation will improve the autonomic control of BP and heart rate in individuals with high abdominal obesity and BP. There is evidence that food high in L-arginine improves baroreflex sensitivity (BRS) in individuals with pre-hypertension. This aim will examine the working hypothesis that watermelon will improve cardiovascular autonomic control of BP by measuring heart rate variability, BP variability and BRS at rest and during physiological stress as secondary variables.
- Conditions
- Hypertension
- Being tested
- Watermelon Extract
- Keywords
- Arterial Stiffness, Wave Reflection, Watermelon Supplementation, Aortic Blood Pressure, Obesity
- Medical subject headings
- Hypertension, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Watermelon ExtractDietary supplement
Also called Watermelon extract from Milne fruit Products Inc
6 weeks of watermelon extract taken in two doses of 3g each per day (6g per day)containing L-citrulline/L-arginine (4/2 g)
| Study group | Role | What they receive |
|---|---|---|
| Maltodextrin | Placebo comparator | 6g/day of placebo (maltodextrin) Receives: Dietary Supplement: Watermelon Extract |
| Watermelon | Experimental | (6g per day)containing L-citrulline/L-arginine (4/2 g) Receives: Dietary Supplement: Watermelon Extract |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Pressure
By measuring brachial and central (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and cold pressor test)
Measured: 12 weeks
Secondary outcomes (4)
Arterial Stiffness
Using pulse wave velocity of the aorta and legs.
Measured: 12 weeks
Endothelial function
By measuring flow-mediated dilation using vascular ultrasound and circulating levels of vasodilators, vasoconstrictors, and markers of vascular inflammation (adiponectin, leptin, endothelin-1, angiotensin II, prostaglandin F2α, sVCAM-1, sICAM-1, and 8-isoprostane).
Measured: 12 weeks
Autonomic control of BP
By measuring BP variability and BRS at rest and during physiological stress
Measured: 12 weeks
Autonomic control of heart rate
By measuring heart rate variability at rest and during physiological stress
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arturo Figueroa, Florida State University
- Investigators
- Arturo Figueroa, MD, PhD, Principal investigator, The Florida State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01185041
- Sponsor's protocol ID
- RF02032
- Status last verified
- Mar 2012
- First submitted
- 17 Aug 2010
- Last updated
- 20 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Figueroa A, Wong A, Kalfon R. Effects of watermelon supplementation on aortic hemodynamic responses to the cold pressor test in obese hypertensive adults. Am J Hypertens. 2014 Jul;27(7):899-906. doi: 10.1093/ajh/hpt295. Epub 2014 Feb 26.
PubMed 24572702
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral L-citrulline/L-arginine in Watermelon on Central Blood Pressure and Arterial Stiffness in Individuals With Obesity-related High Blood Pressure
- ClinicalTrials.gov ID
- NCT01185041
- Acronym / sponsor ID
- RF02032
- Conditions
- Hypertension
- Keywords
- Arterial Stiffness, Wave Reflection, Watermelon Supplementation, Aortic Blood Pressure, Obesity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Florida State UniversityUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 19 Aug 2010 (estimated)
- 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.
Increased abdominal obesity (waist circumference) and systolic blood pressure (BP) are main risk factors for the metabolic syndrome. Approximately 60% of adults in the United States are prehypertensive or hypertensive. Hypertension has been associated with abnormal endothelial and autonomic function, the two main mechanisms of BP regulation. Endothelial dysfunction, as a result of reduced NO (a vasodilator), and increased sympathetic nervous system activity contribute to arterial stiffness by enhancing the vasomotor tone. Because BP variations are sensed by baroreceptors in the wall of large arteries, increased stiffness of arteries may attenuate the control of BP by the autonomic nervous system leading to hypertension. High production of proinflammatory cytokines and low adiponectin (vascular protective molecule), are considered the underlying mechanisms leading to endothelial dysfunction and arterial stiffness. The recommended intervention for controlling BP in overweight/obese individuals with pre- and stage 1- hypertension is lifestyle modifications and not drug therapy. Among the dietary regimens that are reported to reduce BP is L-arginine, the substrate for endothelial NO production. Recently, oral L-citrulline has been shown to be more effective than L-arginine in improving circulating NO levels because is not affected by enzymatic degradation. Watermelon, the leading US melon crop, is one of the few natural foods rich in L-citrulline which is efficiently transformed to arginine in humans. The investigators long-term goal is to provide feasible and effective dietary ways to reduce cardiovascular risk factors in individuals with high abdominal fat and BP. The overall objective of this study is to bring forth evidence that watermelon supplementation will reduce BP and cardiovascular risk factors such as arterial stiffness, autonomic dysfunction and endothelial dysfunction. The investigators postulate that watermelon supplementation will reduce BP and arterial stiffness by enhancing endothelial function and reducing vascular inflammation. The findings of this study will provide a foundation for disseminating feasible, safe approaches for preventing and combating obesity-related hypertension at its early stage which does not require drug therapy.
Detailed description
The purpose of the study is to examine the effect of 12 weeks of L-citrulline/L-arginine in the form of watermelon supplementation on arterial function and autonomic neural control of the heart rate and blood pressure in older overweight/obese men and women with pre- and stage 1- hypertension. The specific aims of the study are:
- To investigate the extent to which daily consumption of watermelon supplementation containing L-citrulline/L-arginine (4/2 g) will reduce BP and arterial stiffness. This aim will examine the working hypothesis that watermelon supplementation will reduce BP and improve arterial function. This aim will be tested by measuring brachial and central (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and cold pressor test), and by evaluating arterial stiffness using pulse wave velocity of the aorta and legs as primary variables.
- To determine the effect of watermelon supplementation on endothelial function. There is evidence that watermelon improves endothelial function in rats. Hence, we postulate that watermelon in part exerts its vascular protective effects by modulating indices of endothelial function. This aim will be tested by measuring flow-mediated dilation using vascular ultrasound and circulating levels of vasodilators, vasoconstrictors, and markers of vascular inflammation (adiponectin, leptin, endothelin-1, angiotensin II, prostaglandin F2α, sVCAM-1, sICAM-1, and 8-isoprostane).
- To determine whether watermelon supplementation will improve the autonomic control of BP and heart rate in individuals with high abdominal obesity and BP. There is evidence that food high in L-arginine improves baroreflex sensitivity (BRS) in individuals with pre-hypertension. This aim will examine the working hypothesis that watermelon will improve cardiovascular autonomic control of BP by measuring heart rate variability, BP variability and BRS at rest and during physiological stress as secondary variables.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maltodextrin | Placebo comparator | Dietary Supplement: Watermelon Extract6g/day of placebo (maltodextrin) |
| Watermelon | Experimental | Dietary Supplement: Watermelon Extract(6g per day)containing L-citrulline/L-arginine (4/2 g) |
Who may qualify
- Ages
- 45 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Thirty men and women 45-70 years of age
- BP between 120-159/80-99 mmHg
- Waist circumference >102 cm in men and > 80 cm in women
Key exclusion criteria (18 listed)
- BP >160/100 mmHg
- Asthma
- Glaucoma
- Herpes simplex
- Uncontrolled diabetes
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 |
|---|---|---|
| Watermelon ExtractAlso: Watermelon extract from Milne fruit Products Inc6 weeks of watermelon extract taken in two doses of 3g each per day (6g per day)containing L-citrulline/L-arginine (4/2 g) | Dietary supplement | Maltodextrin, Watermelon |
Primary outcome
Blood Pressure
Time frame: 12 weeks
By measuring brachial and central (aortic and carotid) BP at rest and during physiological stress (head-up tilt test and cold pressor test)
4 secondary outcomes
Arterial Stiffness
Time frame: 12 weeks
Endothelial function
Time frame: 12 weeks
Autonomic control of BP
Time frame: 12 weeks
Autonomic control of heart rate
Time frame: 12 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 20 Mar 2012.
- Derived from this study: PubMed 24572702Figueroa A, Wong A, Kalfon R. Effects of watermelon supplementation on aortic hemodynamic responses to the cold pressor test in obese hypertensive adults. Am J Hypertens. 2014 Jul;27(7):899-906. doi: 10.1093/ajh/hpt295. Epub 2014 Feb 26.
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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, MD, PhD principal investigator
The Florida State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Watermelon Extract in people with Hypertension, run by Florida State 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 3 inclusion and 18 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 20 Mar 2012. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Blood Pressure (time frame: 12 weeks). 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 NCT01185041, which also lists 1 linked publication.
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 20 Mar 2012.