End Stage Renal DiseaseNCT00863603
The Effect of Oxygen on Healing an Artery From the "Injury" of Surgery
A study testing oxygen in people with End Stage Renal Disease, run by University of Minnesota at 3 sites in United States.
Trial summary
Many grafts placed for dialysis access fail which causes patients to undergo additional operations, decreases their quality of life, and increases health care costs. The purpose of this study is to see if dialysis access grafts will function longer for patients who receive additional oxygen by means of a nasal cannula… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2005to Aug 2009
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-80+/- referred and considered a candidate for a synthetic hemodialysis access graft.
- Baseline room air arterial blood concentration >70 and arterial carbon dioxide concentration 45 mmHg. Pulmonary function tests > 75% predicted values
- Currently undergoing dialysis
- No previous synthetic hemodialysis grafts placed in the same arm (fistula in ipsilateral arm permitted)
- Ability to use 5L/minute supplemental oxygen by nasal cannula
- Nonsmoker, able to avoid other situations which would constitute a risk for use of oxygen
Show all 9Show fewer
- Medical condition with > 1 year life expectancy
- Currently on no medications which would interfere with wound healing (i.e. steroids, chemotherapeutic agents)
- Not pregnant nor planning to become pregnant during study period
Who cannot join
- Failure to meet inclusion criteria
- Failure to comply with study protocol for 3 consecutive days during the 6 wk oxygen/non-oxygen supplement period immediately following graft placement
- Medical condition developing during study period causing a significantly worsening pulmonary function requiring supplemental oxygen for > 3 days
- Need to take medication during study period which would interfere with wound healing any time during the 6 week period immediately following graft placement or need to take chronic medications (> 6 weeks) during the remainder of the study period.
- Patient desire to withdraw
- Failure of evidence of adequate increase in arterial blood oxygen concentration (pa02 > 115 for oxygen supplemented and pa02 > 55 mmHg for control obtained from arterial access port during dialysis run
- Failure to use supplemental oxygen (if in supplemental oxygen group) at least 18 hours per day (as recorded in journal) -
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55401
Veterans Affairs Medical Center
Minneapolis, Minnesota, 55417
University of Minnesota, Division of Vascular Surgery
Minneapolis, Minnesota, 55455
About this study
Official title: Artery Wall Hypoxia and Intimal Hyperplasia
Many grafts placed for dialysis access fail which causes patients to undergo additional operations, decreases their quality of life, and increases health care costs. The purpose of this study is to see if dialysis access grafts will function longer for patients who receive additional oxygen by means of a nasal cannula for 42 days after placement of their graft.
Patients will have periodic blood tests to measure oxygen levels in their blood. A series of ultrasound examinations of patient's dialysis grafts will be taken to ensure the graft is open and to measure the cellular proliferation (intimal hyperplasia) for comparison in those receiving extra oxygen and those with no oxygen.
Read the detailed description
Vascular bypass grafting is a commonly performed procedure in vascular and cardiovascular surgery and the preferred bypass grafts are autogenous vein. Creation of a vascular anastomosis (AVA) is required at 2 sites (proximal and distal anastomoses) for every synthetic bypass graft. It is estimated that 50% of vascular bypass failures are due to anastomotic intimal hyperplasia (AIH). Intimal thickening of the artery wall is a normal response to healing at an anastomosis. Progression of intimal thickening leads to a pathological, hyperplastic, occlusive lesion - AIH, which in turn results in myocardial infarction, stroke, limb loss, death, graft failure, repeat operative procedures, and increased medical costs.
Our laboratory demonstrated in a rabbit model of AIH that: 1) there is a significant decrease in the delivery of oxygen to the peri-anastomotic artery wall following creation of a prosthetic vascular graft to artery anastomosis, 2) the oxygen gradient across the artery wall in the area of a prosthetic vascular graft anastomosis normalizes over a period of 6 weeks as healing occurs, 3) the gradient can be normalized immediately following an anastomosis by the administration of supplemental oxygen, and 4) the amount of AIH and smooth muscle cell proliferation can be reduced by immediately administering supplemental oxygen following creation of the anastomosis.
The long-range goal of our program is to understand the role of oxygen in blood vessel wall pathology. The specific objective of this project, which is the next step in the pursuit of our long-range program goal, is to determine if supplemental oxygen can inhibit AIH in a human graft model.
METHODS: Following review of inclusion and exclusion criteria suitable patients undergo surgical placement of a graft for hemodialysis. Following surgery, patients randomized to oxygen will breathe 5L supplemental oxygen during waking hours for 42 days. Periodic ultrasounds will be taken to assess graft function and patency and to measure intimal thickness. Patients will be followed for two years or until their graft fails.
- Conditions
- End Stage Renal Disease
- Being tested
- oxygen
- Keywords
- Supplemental oxygen, Intimal hyperplasia, Graft patency
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxygenOther
5 Liter/minute by nasal cannula for 6 wks
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | No exposure to supplemental oxygen |
| Oxygen, treatment, supplement | Other | 6 weeks of supplemental oxygen delivered by nasal cannula post hemodialysis graft placement Receives: Other: oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of supplemental oxygen on intimal thickness at the site of a hemodialysis access graft
Measured: Assessing intimal thickness in the first 2 yrs after graft placement
Secondary outcomes (1)
Compare graft patency in oxygen supplemented vs. non oxygen supplemented group
Measured: Assessing graft patency in the first two years after graft placement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2009 (estimated)
- Study startJan 2005
- Primary completionDec 2008
- Study completionAug 2009
Why it stopped: Clinical changes: graft to fistula first; enrollment of 46/132 planned. NIH approved animal model: supplemental oxygen/AV fistula.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven M Santilli, MD, PhD, MBA, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00863603
- Sponsor's protocol ID
- 0010M69621
- Other IDs
- R01HL076316
- Status last verified
- May 2012
- First submitted
- 16 Mar 2009
- Last updated
- 25 May 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Tretinyak AS, Lee ES, Uema KM, d'Audiffret AC, Caldwell MP, Santilli SM. Supplemental oxygen reduces intimal hyperplasia after intraarterial stenting in the rabbit. J Vasc Surg. 2002 May;35(5):982-7. doi: 10.1067/mva.2002.123090.
PubMed 12021715Santilli SM, Wernsing SE, Lee ES. The effect of supplemental oxygen on the transarterial wall oxygen gradients at a prosthetic vascular graft to artery anastomosis in the rabbit. Ann Vasc Surg. 2001 Jul;15(4):435-42. doi: 10.1007/s100160010119.
PubMed 11525533Lee ES, Caldwell MP, Tretinyak AS, Santilli SM. Supplemental oxygen controls cellular proliferation and anastomotic intimal hyperplasia at a vascular graft-to-artery anastomosis in the rabbit. J Vasc Surg. 2001 Mar;33(3):608-13. doi: 10.1067/mva.2001.113495.
PubMed 11241134Santilli SM, Tretinyak AS, Lee ES. Transarterial wall oxygen gradients at the deployment site of an intra-arterial stent in the rabbit. Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1518-25. doi: 10.1152/ajpheart.2000.279.4.H1518.
PubMed 11009436Santilli SM, Wernsing SE, Lee ES. Transarterial wall oxygen gradients at a prosthetic vascular graft to artery anastomosis in the rabbit. J Vasc Surg. 2000 Jun;31(6):1229-39. doi: 10.1067/mva.2000.104590.
PubMed 10842160Lee ES, Bauer GE, Caldwell MP, Santilli SM. Association of artery wall hypoxia and cellular proliferation at a vascular anastomosis. J Surg Res. 2000 Jun 1;91(1):32-7. doi: 10.1006/jsre.2000.5891.
PubMed 10816346Santilli SM, Kronson J, Payne WD. The effect of hypercholesterolemia on the rabbit transarterial wall oxygen gradient. Ann Vasc Surg. 1998 Sep;12(5):418-23. doi: 10.1007/s100169900178.
PubMed 9732418Santilli SM, Kronson JW, Payne WD. Cigarette smoking alters the rabbit transarterial wall oxygen gradient. Ann Vasc Surg. 1998 Mar;12(2):174-81. doi: 10.1007/s100169900137.
PubMed 9514238Santilli SM, Stevens RB, Anderson JG, Caldwell MD. The effect of aging on the transarterial wall oxygen gradient. Ann Vasc Surg. 1995 Mar;9(2):146-51. doi: 10.1007/BF02139656.
PubMed 7786699Santilli SM, Stevens RB, Anderson JG, Payne WD, Caldwell MD. Transarterial wall oxygen gradients at the dog carotid bifurcation. Am J Physiol. 1995 Jan;268(1 Pt 2):H155-61. doi: 10.1152/ajpheart.1995.268.1.H155.
PubMed 7840259Santilli SM, Fiegel VD, Knighton DR. Alloxan diabetes alters the rabbit transarterial wall oxygen gradient. J Vasc Surg. 1993 Aug;18(2):227-33.
PubMed 8350431Santilli SM, Fiegel VD, Knighton DR. Changes in the aortic wall oxygen tensions of hypertensive rabbits. Hypertension and aortic wall oxygen. Hypertension. 1992 Jan;19(1):33-9. doi: 10.1161/01.hyp.19.1.33.
PubMed 1730436Santilli SM, Fiegel VD, Aldridge DE, Knighton DR. Rabbit aortic endothelial cell hypoxia induces secretion of transforming growth factor beta and augments macrophage adhesion in vitro. Ann Vasc Surg. 1991 Sep;5(5):429-38. doi: 10.1007/BF02133047.
PubMed 1958457
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Artery Wall Hypoxia and Intimal Hyperplasia
- ClinicalTrials.gov ID
- NCT00863603
- Acronym / sponsor ID
- 0010M69621
- Conditions
- End Stage Renal Disease
- Keywords
- Supplemental oxygen, Intimal hyperplasia, Graft patency
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Clinical changes: graft to fistula first; enrollment of 46/132 planned. NIH approved animal model: supplemental oxygen/AV fistula.
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 18 Mar 2009 (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.
Many grafts placed for dialysis access fail which causes patients to undergo additional operations, decreases their quality of life, and increases health care costs. The purpose of this study is to see if dialysis access grafts will function longer for patients who receive additional oxygen by means of a nasal cannula for 42 days after placement of their graft.
Patients will have periodic blood tests to measure oxygen levels in their blood. A series of ultrasound examinations of patient's dialysis grafts will be taken to ensure the graft is open and to measure the cellular proliferation (intimal hyperplasia) for comparison in those receiving extra oxygen and those with no oxygen.
Detailed description
Vascular bypass grafting is a commonly performed procedure in vascular and cardiovascular surgery and the preferred bypass grafts are autogenous vein. Creation of a vascular anastomosis (AVA) is required at 2 sites (proximal and distal anastomoses) for every synthetic bypass graft. It is estimated that 50% of vascular bypass failures are due to anastomotic intimal hyperplasia (AIH). Intimal thickening of the artery wall is a normal response to healing at an anastomosis. Progression of intimal thickening leads to a pathological, hyperplastic, occlusive lesion - AIH, which in turn results in myocardial infarction, stroke, limb loss, death, graft failure, repeat operative procedures, and increased medical costs.
Our laboratory demonstrated in a rabbit model of AIH that: 1) there is a significant decrease in the delivery of oxygen to the peri-anastomotic artery wall following creation of a prosthetic vascular graft to artery anastomosis, 2) the oxygen gradient across the artery wall in the area of a prosthetic vascular graft anastomosis normalizes over a period of 6 weeks as healing occurs, 3) the gradient can be normalized immediately following an anastomosis by the administration of supplemental oxygen, and 4) the amount of AIH and smooth muscle cell proliferation can be reduced by immediately administering supplemental oxygen following creation of the anastomosis.
The long-range goal of our program is to understand the role of oxygen in blood vessel wall pathology. The specific objective of this project, which is the next step in the pursuit of our long-range program goal, is to determine if supplemental oxygen can inhibit AIH in a human graft model.
METHODS: Following review of inclusion and exclusion criteria suitable patients undergo surgical placement of a graft for hemodialysis. Following surgery, patients randomized to oxygen will breathe 5L supplemental oxygen during waking hours for 42 days. Periodic ultrasounds will be taken to assess graft function and patency and to measure intimal thickness. Patients will be followed for two years or until their graft fails.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –No exposure to supplemental oxygen |
| Oxygen, treatment, supplement | Other | Other: oxygen6 weeks of supplemental oxygen delivered by nasal cannula post hemodialysis graft placement |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-80+/- referred and considered a candidate for a synthetic hemodialysis access graft.
- Baseline room air arterial blood concentration >70 and arterial carbon dioxide concentration 45 mmHg. Pulmonary function tests > 75% predicted values
- Currently undergoing dialysis
- No previous synthetic hemodialysis grafts placed in the same arm (fistula in ipsilateral arm permitted)
- Ability to use 5L/minute supplemental oxygen by nasal cannula
Key exclusion criteria (7 listed)
- Failure to meet inclusion criteria
- Failure to comply with study protocol for 3 consecutive days during the 6 wk oxygen/non-oxygen supplement period immediately following graft placement
- Medical condition developing during study period causing a significantly worsening pulmonary function requiring supplemental oxygen for > 3 days
- Need to take medication during study period which would interfere with wound healing any time during the 6 week period immediately following graft placement or need to take chronic medications (> 6 weeks) during the remainder of the study period.
- Patient desire to withdraw
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 |
|---|---|---|
| oxygen5 Liter/minute by nasal cannula for 6 wks | Other | Oxygen, treatment, supplement |
Primary outcome
The effect of supplemental oxygen on intimal thickness at the site of a hemodialysis access graft
Time frame: Assessing intimal thickness in the first 2 yrs after graft placement
1 secondary outcome
Compare graft patency in oxygen supplemented vs. non oxygen supplemented group
Time frame: Assessing graft patency in the first two years after graft placement
Results and safety
The study was stopped early (reason given: Clinical changes: graft to fistula first; enrollment of 46/132 planned. NIH approved animal model: supplemental oxygen/AV fistula.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2012.
- Background: PubMed 12021715Tretinyak AS, Lee ES, Uema KM, d'Audiffret AC, Caldwell MP, Santilli SM. Supplemental oxygen reduces intimal hyperplasia after intraarterial stenting in the rabbit. J Vasc Surg. 2002 May;35(5):982-7. doi: 10.1067/mva.2002.123090.
- Background: PubMed 11525533Santilli SM, Wernsing SE, Lee ES. The effect of supplemental oxygen on the transarterial wall oxygen gradients at a prosthetic vascular graft to artery anastomosis in the rabbit. Ann Vasc Surg. 2001 Jul;15(4):435-42. doi: 10.1007/s100160010119.
- Background: PubMed 11241134Lee ES, Caldwell MP, Tretinyak AS, Santilli SM. Supplemental oxygen controls cellular proliferation and anastomotic intimal hyperplasia at a vascular graft-to-artery anastomosis in the rabbit. J Vasc Surg. 2001 Mar;33(3):608-13. doi: 10.1067/mva.2001.113495.
- Background: PubMed 11009436Santilli SM, Tretinyak AS, Lee ES. Transarterial wall oxygen gradients at the deployment site of an intra-arterial stent in the rabbit. Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1518-25. doi: 10.1152/ajpheart.2000.279.4.H1518.
- Background: PubMed 10842160Santilli SM, Wernsing SE, Lee ES. Transarterial wall oxygen gradients at a prosthetic vascular graft to artery anastomosis in the rabbit. J Vasc Surg. 2000 Jun;31(6):1229-39. doi: 10.1067/mva.2000.104590.
- Background: PubMed 10816346Lee ES, Bauer GE, Caldwell MP, Santilli SM. Association of artery wall hypoxia and cellular proliferation at a vascular anastomosis. J Surg Res. 2000 Jun 1;91(1):32-7. doi: 10.1006/jsre.2000.5891.
- Background: PubMed 9732418Santilli SM, Kronson J, Payne WD. The effect of hypercholesterolemia on the rabbit transarterial wall oxygen gradient. Ann Vasc Surg. 1998 Sep;12(5):418-23. doi: 10.1007/s100169900178.
- Background: PubMed 9514238Santilli SM, Kronson JW, Payne WD. Cigarette smoking alters the rabbit transarterial wall oxygen gradient. Ann Vasc Surg. 1998 Mar;12(2):174-81. doi: 10.1007/s100169900137.
- Background: PubMed 7786699Santilli SM, Stevens RB, Anderson JG, Caldwell MD. The effect of aging on the transarterial wall oxygen gradient. Ann Vasc Surg. 1995 Mar;9(2):146-51. doi: 10.1007/BF02139656.
- Background: PubMed 7840259Santilli SM, Stevens RB, Anderson JG, Payne WD, Caldwell MD. Transarterial wall oxygen gradients at the dog carotid bifurcation. Am J Physiol. 1995 Jan;268(1 Pt 2):H155-61. doi: 10.1152/ajpheart.1995.268.1.H155.
- Background: PubMed 8350431Santilli SM, Fiegel VD, Knighton DR. Alloxan diabetes alters the rabbit transarterial wall oxygen gradient. J Vasc Surg. 1993 Aug;18(2):227-33.
- Background: PubMed 1730436Santilli SM, Fiegel VD, Knighton DR. Changes in the aortic wall oxygen tensions of hypertensive rabbits. Hypertension and aortic wall oxygen. Hypertension. 1992 Jan;19(1):33-9. doi: 10.1161/01.hyp.19.1.33.
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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.
Steven M Santilli, MD, PhD, MBA principal investigator
University of Minnesota
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing oxygen in people with End Stage Renal Disease, run by University of Minnesota at 3 sites 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 9 inclusion and 7 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 25 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. 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 stopped early (reason given: Clinical changes: graft to fistula first; enrollment of 46/132 planned. NIH approved animal model: supplemental oxygen/AV fistula.). Results are not available in the source record.
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?
The effect of supplemental oxygen on intimal thickness at the site of a hemodialysis access graft (time frame: Assessing intimal thickness in the first 2 yrs after graft placement). 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 NCT00863603, which also lists 13 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 25 May 2012; AzTrials last refreshed its copy on 7 Nov 2026.