HealthyNCT00583388
The Role of L-arginine in the Endothelial Dysfunction
An observational study of Healthy, run by Mayo Clinic.
Trial summary
Acute cardiac and vascular events, like heart attack and sudden cardiac death manifest a clear surge in the early morning hours around the time of waking, so that their peak onset is between 6AM and 11AM. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- L-arginine and Ultrasound
- Type of treatment
- Pill or oral medicine, Medical device
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2010to Jun 2010
- Phase
- Observational
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: community sample
Who may be able to join
- healthy subjects
Who cannot join
- renal disease; liver disease, sleep disorders, smokers, using chronic medications
About this study
Official title: The Efficacy of L-arginine in Preventing Early Morning Endothelial Dysfunction
Acute cardiac and vascular events, like heart attack and sudden cardiac death manifest a clear surge in the early morning hours around the time of waking, so that their peak onset is between 6AM and 11AM. The mechanisms are not fully understood, but we had shown that healthy subjects have impaired vascular reactivity in the early morning (endothelial dysfunction). This is associated with a decrease in nitric oxide levels (a substance that promotes vasodilatation). We also have described that vessel reactivity and the levels of this substance can recover by noon only when people breakfast.
L-arginine is a semi-essential amino acid found in large quantities in chicken, in fish, and beans and is the substrate for the production of nitric oxide Therefore we want to test if there is a beneficial effect of administration of L-arginine on the circadian pattern of vessel reactivity. Our goal is to understand why cardiovascular events are more likely to happen in the early morning and how to prevent.
The research will help us to understand the efficacy, acute effects and tolerability of high doses of L-arginine. This can lead to future research to assess long term effects of L-arginine supplements to prevent cardiovascular events in the early morning hours.
Read the detailed description
Acute cardiac and vascular events, including sudden cardiac death, myocardial infarction, and stroke manifest a clear surge in the early morning hours around the time of waking, so that their peak onset is between 6 AM and 11AM. The mechanisms for this morning increase in acute cardiovascular events are not fully understood. Factors such as arousal from sleep, increased sympathetic drive, increased vasoconstrictor sensitivity and impaired endothelial function have been implicated.
We recently described the occurrence of early morning endothelial dysfunction, with blunted flow-mediated arterial dilatation in the early hours after waking. Our preliminary data suggest that this early morning endothelial dysfunction is likely due to an increased plasma levels of L-arginine endogenous inhibitor, ADMA and reducted plasma L-arginine levels, with consequent reduced availability of NO in the morning. The early morning fall in NOx levels can be potentiated by fasting and attenuated by a low-nitrate, protein rich breakfast. Because the production of NO depends in part on the availability of L-arginine, methods to maintain an adequate level of plasma L-arginine in the early morning are needed. We propose to assess the efficacy of high doses of L-arginine in preventing early morning endothelial dysfunction.
The primary aim is to examine the effects of high doses of L-arginine on morning changes in nitric oxide and endothelial function. Our hypotheses are:
- That L-arginine administered orally prior to sleep will prevent the early morning decline in plasma levels of L-arginine and nitric oxide; 2. That L-arginine administered prior to sleep will attenuate or prevent the early morning decline in endothelial function; and 3. That the effects of L-arginine, taken prior to sleep, on plasma levels of L-arginine and nitric oxide and on endothelial function will be more marked with 15 grams of L-arginine versus 5 grams of L-arginine or placebo, indicative of a dose response effect.
Our secondary aim is to identify the short-term tolerability and safety of two different doses of L-arginine. Our hypothesis is that subjects taking high doses of L-arginine (15 grams) will not have significant symptoms or adverse changes in vital signs.
- Conditions
- Healthy
- Being tested
- L-arginine, Ultrasound
- Keywords
- cardiology, preventive medicine, cardiovascular physiology, healthy subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDietary supplement
Each subject will be exposed to three treatments, a) 5 g of L-arginine, b) 15 g of L-arginine, and c) placebo, the sequences will be randomly assigned to the 42 volunteers. The washout period between interventions will be from one to two days.L-arginine will be mixed in 60 cc of dextrose-based syrup to blind the taste and color of the L-arginine powder.
UltrasoundDevice
Ultrasound from the brachial artery will be done on 3 occasions: at 9 pm after 4hs of fasting, at 6 am and at 11 am. The brachial artery images will be acquired above the antecubital fossa in the longitudinal plane of the artery with an ultrasound machine using a 6-MHz linear transducer. Flow-mediated vasodilatation will be assessed by the reactive hyperemia method (inflation of a blood pressure cuff around the forearm to 200 mmHg for 5 minutes and then released). The diameter of the brachial artery will be assessed 60 to 90 s after deflation of the cuff. After a 10min period a second baseline image of the brachial artery will be obtained. Non-low-mediated vasodilatation will be measured by an administration of a sublingual dose of nitroglycerin (0.4 mg).
| Study group | Role | What they receive |
|---|---|---|
| A | 42 healthy subjects aged 18 to 60 will be be randomly assigned to 6 different treatment sequences. Receives: Dietary Supplement: L-arginine; Device: Ultrasound |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2007 (estimated)
- Study startJun 2010
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: PI is leaving the Institution, IRB will close the protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Investigators
- Virend K Somers, MD, PhD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00583388
- Sponsor's protocol ID
- 06-008907
- Status last verified
- Apr 2015
- First submitted
- 20 Dec 2007
- Last updated
- 28 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of L-arginine in Preventing Early Morning Endothelial Dysfunction
- ClinicalTrials.gov ID
- NCT00583388
- Acronym / sponsor ID
- 06-008907
- Conditions
- Healthy
- Keywords
- cardiology, preventive medicine, cardiovascular physiology, healthy subjects
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: PI is leaving the Institution, IRB will close the protocol.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 31 Dec 2007 (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.
Acute cardiac and vascular events, like heart attack and sudden cardiac death manifest a clear surge in the early morning hours around the time of waking, so that their peak onset is between 6AM and 11AM. The mechanisms are not fully understood, but we had shown that healthy subjects have impaired vascular reactivity in the early morning (endothelial dysfunction). This is associated with a decrease in nitric oxide levels (a substance that promotes vasodilatation). We also have described that vessel reactivity and the levels of this substance can recover by noon only when people breakfast.
L-arginine is a semi-essential amino acid found in large quantities in chicken, in fish, and beans and is the substrate for the production of nitric oxide Therefore we want to test if there is a beneficial effect of administration of L-arginine on the circadian pattern of vessel reactivity. Our goal is to understand why cardiovascular events are more likely to happen in the early morning and how to prevent.
The research will help us to understand the efficacy, acute effects and tolerability of high doses of L-arginine. This can lead to future research to assess long term effects of L-arginine supplements to prevent cardiovascular events in the early morning hours.
Detailed description
Acute cardiac and vascular events, including sudden cardiac death, myocardial infarction, and stroke manifest a clear surge in the early morning hours around the time of waking, so that their peak onset is between 6 AM and 11AM. The mechanisms for this morning increase in acute cardiovascular events are not fully understood. Factors such as arousal from sleep, increased sympathetic drive, increased vasoconstrictor sensitivity and impaired endothelial function have been implicated.
We recently described the occurrence of early morning endothelial dysfunction, with blunted flow-mediated arterial dilatation in the early hours after waking. Our preliminary data suggest that this early morning endothelial dysfunction is likely due to an increased plasma levels of L-arginine endogenous inhibitor, ADMA and reducted plasma L-arginine levels, with consequent reduced availability of NO in the morning. The early morning fall in NOx levels can be potentiated by fasting and attenuated by a low-nitrate, protein rich breakfast. Because the production of NO depends in part on the availability of L-arginine, methods to maintain an adequate level of plasma L-arginine in the early morning are needed. We propose to assess the efficacy of high doses of L-arginine in preventing early morning endothelial dysfunction.
The primary aim is to examine the effects of high doses of L-arginine on morning changes in nitric oxide and endothelial function. Our hypotheses are:
- That L-arginine administered orally prior to sleep will prevent the early morning decline in plasma levels of L-arginine and nitric oxide; 2. That L-arginine administered prior to sleep will attenuate or prevent the early morning decline in endothelial function; and 3. That the effects of L-arginine, taken prior to sleep, on plasma levels of L-arginine and nitric oxide and on endothelial function will be more marked with 15 grams of L-arginine versus 5 grams of L-arginine or placebo, indicative of a dose response effect.
Our secondary aim is to identify the short-term tolerability and safety of two different doses of L-arginine. Our hypothesis is that subjects taking high doses of L-arginine (15 grams) will not have significant symptoms or adverse changes in vital signs.
Study design
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | – | Dietary Supplement: L-arginine, Device: Ultrasound42 healthy subjects aged 18 to 60 will be be randomly assigned to 6 different treatment sequences. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- community sample
Key inclusion criteria (1 listed)
- healthy subjects
Key exclusion criteria (1 listed)
- renal disease; liver disease, sleep disorders, smokers, using chronic medications
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-arginineEach subject will be exposed to three treatments, a) 5 g of L-arginine, b) 15 g of L-arginine, and c) placebo, the sequences will be randomly assigned to the 42 volunteers. The washout period between interventions will be from one to two days.L-arginine will be mixed in 60 cc of dextrose-based syrup to blind the taste and color of the L-arginine powder. | Dietary supplement | A |
| UltrasoundUltrasound from the brachial artery will be done on 3 occasions: at 9 pm after 4hs of fasting, at 6 am and at 11 am. The brachial artery images will be acquired above the antecubital fossa in the longitudinal plane of the artery with an ultrasound machine using a 6-MHz linear transducer. Flow-mediated vasodilatation will be assessed by the reactive hyperemia method (inflation of a blood pressure cuff around the forearm to 200 mmHg for 5 minutes and then released). The diameter of the brachial artery will be assessed 60 to 90 s after deflation of the cuff. After a 10min period a second baseline image of the brachial artery will be obtained. Non-low-mediated vasodilatation will be measured by an administration of a sublingual dose of nitroglycerin (0.4 mg). | Device | A |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2015.
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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.
Virend K Somers, MD, PhD study chair
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by Mayo Clinic.
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 1 inclusion and 1 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: withdrawn, as of the sponsor's last update on 28 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 was withdrawn before enrolling participants, so there are no results.
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.
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 28 Apr 2015.