Peripheral Arterial DiseasePhase 1NCT00491751
Clinical Utility of Endothelial Dysfunction in PAD
A Phase 1 study testing atorvastatin and ascorbic acid in people with Peripheral Arterial Disease, run by Boston University at 1 site in United States.
Trial summary
This study will seek to determine whether non-invasive measures of endothelial function have utility as surrogate markers of cardiovascular risk in patients with peripheral arterial disease undergoing vascular surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- atorvastatin and ascorbic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Jun 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects age 21-99 years old.
- Peripheral Arterial Disease. PAD is defined clinically and by angiography, magnetic resonance imaging, vascular ultrasound, or ankle brachial index less than 0.9.
- Able to provide informed consent and complete the study procedure.
- Patients undergoing non-emergent vascular surgery (peripheral arterial bypass, abdominal aortic aneurysm repair, carotid endarterectomy, or limb amputation) or other non-cardiac surgery.
Who cannot join
- Emergent or urgent surgery that must be performed sooner than one week after enrollment
- Unstable angina, myocardial infarction, stroke, coronary revascularization, or decompensated heart failure within 1 month of enrollment. Patients who require cardiac catheterization and surgical or percutaneous coronary revascularization prior to vascular surgery will be excluded.
- Clinically evident major illness of other organ systems, including cancer, end-stage renal disease, hepatic failure, or other conditions that make participation inappropriate.
- Women who are lactating, pregnant, or of childbearing potential and not using a reliable contraceptive method. Pregnancy will be excluded by a urine pregnancy test.
- Patients with liver function tests or serum creatine kinase >3 times the upper limit of normal.
- Patients who have received an investigational drug within 30 days of enrollment.
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- Patients or subjects with a history of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.
- Known occlusive atherosclerosis of the subclavian artery or upper extremity, because such disease will interfere with induction of reactive hyperemia during the brachial artery ultrasound studies.
- Patients will be excluded if they are taking vitamin C in a dose greater than 2 times the Recommended Daily Allowance (>120 mg/day) within 1 month of enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
This study will seek to determine whether non-invasive measures of endothelial function have utility as surrogate markers of cardiovascular risk in patients with peripheral arterial disease undergoing vascular surgery. Measurements of endothelial function will be made before and after initiation of atorvastatin, ascorbic acid, or placebo therapy during the pre-operative period. We will then examine cardiovascular events following surgery. We hypothesize that patients who have no improvement in endothelial function will have increased cardiovascular risk compared to patients with improvement in endothelial function.
Read the detailed description
Part 1 of the study will involve only patients with PAD who are undergoing non-cardiac surgery and is an intervention study. Part 2 will involve patients with PAD who have participated in Part 1 and patients with PAD who are not undergoing surgery. This part of the study does not involve an intervention.
The protocol for patients undergoing surgery is as follows: Part 1. Intervention study with follow-up for 30 days after surgery. Patients with planned surgery will be enrolled. We will test endothelial function at baseline using ultrasound and tonometry. They will then be randomzied to one of three groups: Atorvastatin 80 mg/d, Vitamin C 500 mg/d, or placebo. Subjects already on a statin medication at the time of enrollment will receive 40 mg/d of atorvastatin. Patients taking high dose statin (>40 mg/day) will be randomized to received vitamin C or placebo, and will not be eligible to receive any additional statin as part of the study. In the week immediately prior to surgery, we will test endothelial function a second time. They will then be followed for 30 days beginning with the day of surgery for cardiovascular events. Part 1 of the study involves 4 visits as follows: Visit 1 at enrollment will take place within 7-30 days of non-emergent vascular surgery and will last approximately 60 minutes Visit 2 will take place within approximately 1 week of surgery and will last approximately 30-40 minutes Visit 3 will occur on the 1st post-operative day and will last approximately 10-15 minutes Visit 4 will take place only if the subject is still an in-patient. It will take approximately 10-15 minutes Telephone contact will occur at 30 days post surgery and every six months thereafter for two years. The duration of telephone follow-up is expected to be approximately 5-10 minutes. Part 2 (long term follow-up): Patients who have completed Part 1 will be continued on in Part 2 of the study. Part 2 involves two year follow-up with no study medication. Telephone contact will be made every 6 months. subjects will make a visit to our research unit one year after the initial visit for physical examination, and if applicable, an ultrasound study of their bypass grafts.
The protocol for patients with PAD who are not undergoing surgery is as follows. These patients will participate in Part 2 of the study only (long-term follow-up with no intervention). Visit 1: will last approximately 60 minutes and involve measurement of endothelial function by ultrasound and tonometry. We will contact the subject every 6 months by telephone (5-10 minutes) for two years to determine whether a cardiovascular event has occurred. Visit 2 will occur at 1 year post enrollment and will last approximately 20-30 minutes. If the subject has had peripheral bypass surgery, we will perform an ultrasound study to determine graft blood flow.
- Conditions
- Peripheral Arterial Disease
- Being tested
- atorvastatin, ascorbic acid, Placebo
- Keywords
- endothelium, nitric oxide, statins, ascorbic acid
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatinDrug
Also called Lipitor
atorvastatin 40 or 80 mg/day
ascorbic acidDrug
Also called Vitamin C
ascorbic acid 500 mg/day
PlaceboDrug
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Experimental | Atorvastatin 40 or 80 mg/day Receives: Drug: atorvastatin |
| Ascorbic Acid | Experimental | Ascorbic Acid 500 mg/day Receives: Drug: ascorbic acid |
| Placebo | Placebo comparator | Placebo atorvastatin and Placebo ascorbic acid Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FMD
Change in flow mediated dilation with treatment: FMD visit 2 - FMD visit 1 FMD is measured by using vascular ultrasound to determine the baseline diameter of the brachial artery. Endothelium-dependent vasodilation is induced by 5-minute arterial occlusion with a blood pressure cuff. When the cuff is released, the resultant increase in blood flow (reactive hyperemia) stimulates vasodilation of the brachial artery. This flow-mediated dilation (FMD) is expressed as the percent change from baseline. Healthy individuals typical dysplay a 10 to 12% dilation. Individuals with PAD had markedly impaired dilation of 6-7. The currernt study sought to determine whether a change in FMD would occur following intervention.
Measured: 1-4 weeks
Secondary outcomes (1)
Percentage Change in FMD in All Participants With and Without a CVD Event (Not by Treatment Group)
This outcome is independent of the treatment group so the groups are 'CVD event' and ' No CVD Event'. Cardiovascular events (CVD) included cardiovascular disease, myocardial infarction, congestive heart failure, stroke, and unstable angina.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2007 (estimated)
- Study startMay 2004
- Primary completionJun 2012
- Study completionJun 2012
Why it stopped: Insufficient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by Boston UniversityThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Naomi Hamburg, MD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00491751
- Sponsor's protocol ID
- H-23184
- Status last verified
- May 2017
- First submitted
- 22 Jun 2007
- Last updated
- 27 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Utility of Endothelial Dysfunction in PAD
- ClinicalTrials.gov ID
- NCT00491751
- Acronym / sponsor ID
- H-23184
- Conditions
- Peripheral Arterial Disease
- Keywords
- endothelium, nitric oxide, statins, ascorbic acid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient enrollment
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Study start
- May 2004
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 26 Jun 2007 (estimated)
- Results
- Posted 27 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will seek to determine whether non-invasive measures of endothelial function have utility as surrogate markers of cardiovascular risk in patients with peripheral arterial disease undergoing vascular surgery. Measurements of endothelial function will be made before and after initiation of atorvastatin, ascorbic acid, or placebo therapy during the pre-operative period. We will then examine cardiovascular events following surgery. We hypothesize that patients who have no improvement in endothelial function will have increased cardiovascular risk compared to patients with improvement in endothelial function.
Detailed description
Part 1 of the study will involve only patients with PAD who are undergoing non-cardiac surgery and is an intervention study. Part 2 will involve patients with PAD who have participated in Part 1 and patients with PAD who are not undergoing surgery. This part of the study does not involve an intervention.
The protocol for patients undergoing surgery is as follows: Part 1. Intervention study with follow-up for 30 days after surgery. Patients with planned surgery will be enrolled. We will test endothelial function at baseline using ultrasound and tonometry. They will then be randomzied to one of three groups: Atorvastatin 80 mg/d, Vitamin C 500 mg/d, or placebo. Subjects already on a statin medication at the time of enrollment will receive 40 mg/d of atorvastatin. Patients taking high dose statin (>40 mg/day) will be randomized to received vitamin C or placebo, and will not be eligible to receive any additional statin as part of the study. In the week immediately prior to surgery, we will test endothelial function a second time. They will then be followed for 30 days beginning with the day of surgery for cardiovascular events. Part 1 of the study involves 4 visits as follows: Visit 1 at enrollment will take place within 7-30 days of non-emergent vascular surgery and will last approximately 60 minutes Visit 2 will take place within approximately 1 week of surgery and will last approximately 30-40 minutes Visit 3 will occur on the 1st post-operative day and will last approximately 10-15 minutes Visit 4 will take place only if the subject is still an in-patient. It will take approximately 10-15 minutes Telephone contact will occur at 30 days post surgery and every six months thereafter for two years. The duration of telephone follow-up is expected to be approximately 5-10 minutes. Part 2 (long term follow-up): Patients who have completed Part 1 will be continued on in Part 2 of the study. Part 2 involves two year follow-up with no study medication. Telephone contact will be made every 6 months. subjects will make a visit to our research unit one year after the initial visit for physical examination, and if applicable, an ultrasound study of their bypass grafts.
The protocol for patients with PAD who are not undergoing surgery is as follows. These patients will participate in Part 2 of the study only (long-term follow-up with no intervention). Visit 1: will last approximately 60 minutes and involve measurement of endothelial function by ultrasound and tonometry. We will contact the subject every 6 months by telephone (5-10 minutes) for two years to determine whether a cardiovascular event has occurred. Visit 2 will occur at 1 year post enrollment and will last approximately 20-30 minutes. If the subject has had peripheral bypass surgery, we will perform an ultrasound study to determine graft blood flow.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Experimental | Drug: atorvastatinAtorvastatin 40 or 80 mg/day |
| Ascorbic Acid | Experimental | Drug: ascorbic acidAscorbic Acid 500 mg/day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo atorvastatin and Placebo ascorbic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female subjects age 21-99 years old.
- Peripheral Arterial Disease. PAD is defined clinically and by angiography, magnetic resonance imaging, vascular ultrasound, or ankle brachial index less than 0.9.
- Able to provide informed consent and complete the study procedure.
- Patients undergoing non-emergent vascular surgery (peripheral arterial bypass, abdominal aortic aneurysm repair, carotid endarterectomy, or limb amputation) or other non-cardiac surgery.
Key exclusion criteria (9 listed)
- Emergent or urgent surgery that must be performed sooner than one week after enrollment
- Unstable angina, myocardial infarction, stroke, coronary revascularization, or decompensated heart failure within 1 month of enrollment. Patients who require cardiac catheterization and surgical or percutaneous coronary revascularization prior to vascular surgery will be excluded.
- Clinically evident major illness of other organ systems, including cancer, end-stage renal disease, hepatic failure, or other conditions that make participation inappropriate.
- Women who are lactating, pregnant, or of childbearing potential and not using a reliable contraceptive method. Pregnancy will be excluded by a urine pregnancy test.
- Patients with liver function tests or serum creatine kinase >3 times the upper limit of normal.
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 |
|---|---|---|
| atorvastatinAlso: Lipitoratorvastatin 40 or 80 mg/day | Drug | Atorvastatin |
| ascorbic acidAlso: Vitamin Cascorbic acid 500 mg/day | Drug | Ascorbic Acid |
| Placebomatching placebo | Drug | Placebo |
Primary outcome
Change in FMD
Time frame: 1-4 weeks
Change in flow mediated dilation with treatment: FMD visit 2 - FMD visit 1 FMD is measured by using vascular ultrasound to determine the baseline diameter of the brachial artery. Endothelium-dependent vasodilation is induced by 5-minute arterial occlusion with a blood pressure cuff. When the cuff is released, the resultant increase in blood flow (reactive hyperemia) stimulates vasodilation of the brachial artery. This flow-mediated dilation (FMD) is expressed as the percent change from baseline. Healthy individuals typical dysplay a 10 to 12% dilation. Individuals with PAD had markedly impaired dilation of 6-7. The currernt study sought to determine whether a change in FMD would occur following intervention.
1 secondary outcome
Percentage Change in FMD in All Participants With and Without a CVD Event (Not by Treatment Group)
Time frame: 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Naomi Hamburg, MD principal investigator
Boston 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 study testing atorvastatin and ascorbic acid in people with Peripheral Arterial Disease, run by Boston 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 4 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: stopped early, as of the sponsor's last update on 27 Jul 2018. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 FMD (time frame: 1-4 weeks). 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 27 Jul 2018; AzTrials last refreshed its copy on 6 Nov 2026.