Cardiovascular DiseasesNCT00005338
Homocysteine and Progression of Atherosclerosis
An observational study of Cardiovascular Diseases and Peripheral Vascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
In the first phase, to establish the relationship of progression of peripheral vascular disease (PVD) to plasma homocysteine. In the second phase, to conduct a randomized, controlled trial of folic acid treatment of plasma homocysteine in peripheral vascular disease. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Aug 1991to Aug 2004
- 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 Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
In the first phase, to establish the relationship of progression of peripheral vascular disease (PVD) to plasma homocysteine. In the second phase, to conduct a randomized, controlled trial of folic acid treatment of plasma homocysteine in peripheral vascular disease.
Read the detailed description
BACKGROUND:
Few studies of progression of atherosclerotic peripheral vascular disease have been performed and none have used objective methods to evaluate disease progression in a large number of symptomatic subjects. The study is of obvious major clinical importance. Elevated plasma homocysteine is well established as an independent risk factor for atherosclerosis. If folate treatment results in less frequent/rapid progression of peripheral vascular disease, then it will be confirmed as the first effective treatment for atherosclerosis which is without toxic side effects and does not involve major changes in life/dietary habits.
DESIGN NARRATIVE:
The Homocysteine and Progression of Atherosclerosis Study (HPAS) is a long term, prospective, blinded, multifactoral clinical study which began in 1991 to study the relationship between elevated plasma homocysteine (HC) as well as a number of other risk factors and PVD progression. The study is divided into two phases, conducted sequentially upon 400 patients with symptomatic lower extremity (LED) and cerebrovascular disease (CVD). The first phase was a three year natural history study in which relationship of progression of peripheral vascular disease to plasma homocysteine and other risk factors was established. The clinical question addressed by the natural history study was: Do patients with symptomatic peripheral vascular disease and elevated plasma homocysteine have more rapid/frequent progression of peripheral vascular disease than patients with symptomatic peripheral vascular disease and normal plasma homocysteine? Progression of disease was assessed by the primary outcome variables of ankle brachial pressure index and degree of carotid artery stenosis, as determined in the noninvasive vascular laboratory, and by secondary outcome variables including vascular death, need for vascular surgery, stroke, myocardial infarction, amputation, and other clinical events. All outcome variables were determined by investigators blinded to the results of plasma homocysteine testing.
The second phase of the study, which began in August, 1995, is a blinded, prospective, randomized, placebo-controlled trial of folic acid treatment of elevated plasma homocysteine in the same patient population. Folic acid treatment has been demonstrated to result in normalization of elevated plasma homocysteine. The treatment trial addresses the clinical question: Do patients with symptomatic peripheral vascular disease and elevated plasma homocysteine treated with folate have less frequent/rapid progression of peripheral vascular disease than patients with symptomatic peripheral vascular disease and elevated plasma homocysteine treated with placebo? Although the second phase is described as a clinical trial, the Surgery and Bioengineering Study Section describes it as clinical research, not an NIH-defined Phase III trial.
The study was renewed in FY 1999 through 2003 to continue follow-up and analysis.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
- Conditions
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis, Cerebrovascular Disorders, Myocardial Infarction, Heart Diseases
- Medical subject headings
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis, Cerebrovascular Disorders, Myocardial Infarction, Heart Diseases, Hyperhomocysteinemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startAug 1991
- Study completionAug 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Time perspective
- Retrospective
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Lloyd Taylor, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005338
- Sponsor's protocol ID
- 4200
- Other IDs
- R01HL045267
- Status last verified
- Dec 2004
- First submitted
- 25 May 2000
- Last updated
- 18 Feb 2016
- Results posted
- No
Publications
McLafferty RB, Moneta GL, Passman MA, Brant BM, Taylor LM Jr, Porter JM. Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg. 1998 Jan;27(1):50-6; discussion 56-7. doi: 10.1016/s0741-5214(98)70291-5.
PubMed 9474082Nehler MR, Taylor LM Jr, Porter JM. Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Surg. 1997 Dec;5(6):559-67. doi: 10.1177/096721099700500603.
PubMed 9423939Abou-Zamzam AM Jr, Lee RW, Moneta GL, Taylor LM Jr, Porter JM. Functional outcome after infrainguinal bypass for limb salvage. J Vasc Surg. 1997 Feb;25(2):287-95; discussion 295-7. doi: 10.1016/s0741-5214(97)70350-1.
PubMed 9052563Lee RW, Taylor LM Jr, Landry GJ, Goodnight SH, Moneta GL, Edwards JM, Yeager RA, Porter JM. Prospective comparison of infrainguinal bypass grafting in patients with and without antiphospholipid antibodies. J Vasc Surg. 1996 Oct;24(4):524-31; discussion 531-3. doi: 10.1016/s0741-5214(96)70068-x.
PubMed 8911401McLafferty RB, Moneta GL, Masser PA, Taylor LM Jr, Porter JM. Progression of atherosclerosis in arteries distal to lower extremity revascularizations. J Vasc Surg. 1995 Oct;22(4):450-5; discussion 455-6. doi: 10.1016/s0741-5214(95)70014-5.
PubMed 7563406McLafferty RB, Moneta GL, Taylor LM Jr, Porter JM. Ability of ankle-brachial index to detect lower-extremity atherosclerotic disease progression. Arch Surg. 1997 Aug;132(8):836-40; discussion 840-1. doi: 10.1001/archsurg.1997.01430320038005.
PubMed 9267266Deloughery TG, Evans A, Sadeghi A, McWilliams J, Henner WD, Taylor LM Jr, Press RD. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease. Circulation. 1996 Dec 15;94(12):3074-8. doi: 10.1161/01.cir.94.12.3074.
PubMed 8989110Nehler MR, Moneta GL, Lee RW, Edwards JM, Taylor LM Jr, Porter JM. Improving selection of patients with less than 60% asymptomatic internal carotid artery stenosis for follow-up carotid artery duplex scanning. J Vasc Surg. 1996 Oct;24(4):580-5; discussion 585-7. doi: 10.1016/s0741-5214(96)70073-3.
PubMed 8911406Masser PA, Taylor LM Jr, Porter JM. Importance of elevated plasma homocysteine levels as a risk factor for atherosclerosis. Ann Thorac Surg. 1994 Oct;58(4):1240-6. doi: 10.1016/0003-4975(94)90522-3.
PubMed 7944799Taylor LM Jr, Chitwood RW, Dalman RL, Sexton G, Goodnight SH, Porter JM. Antiphospholipid antibodies in vascular surgery patients. A cross-sectional study. Ann Surg. 1994 Oct;220(4):544-50; discussion 550-1. doi: 10.1097/00000658-199410000-00012.
PubMed 7944664Taylor LM Jr, Park TC, Edwards JM, Yeager RA, McConnell DC, Moneta GA, Porter JM. Acute disruption of polytetrafluoroethylene grafts adjacent to axillary anastomoses: a complication of axillofemoral grafting. J Vasc Surg. 1994 Oct;20(4):520-6; discussion 526-8. doi: 10.1016/0741-5214(94)90276-3.
PubMed 7933253Jacobsen DW, Gatautis VJ, Green R, Robinson K, Savon SR, Secic M, Ji J, Otto JM, Taylor LM Jr. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem. 1994 Jun;40(6):873-81.
PubMed 8087981Taylor LM Jr, Porter JM. Elevated plasma homocysteine as a risk factor for atherosclerosis. Semin Vasc Surg. 1993 Mar;6(1):36-45. No abstract available.
PubMed 8252227Nicoloff AD, Taylor LM Jr, McLafferty RB, Moneta GL, Porter JM. Patient recovery after infrainguinal bypass grafting for limb salvage. J Vasc Surg. 1998 Feb;27(2):256-63; discussion 264-6. doi: 10.1016/s0741-5214(98)70356-8.
PubMed 9510280Taylor LM Jr, Moneta GL, Sexton GJ, Schuff RA, Porter JM. Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease. J Vasc Surg. 1999 Jan;29(1):8-19; discussion 19-21. doi: 10.1016/s0741-5214(99)70345-9.
PubMed 9925456
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Homocysteine and Progression of Atherosclerosis
- ClinicalTrials.gov ID
- NCT00005338
- Acronym / sponsor ID
- 4200
- Conditions
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis, Cerebrovascular Disorders, Myocardial Infarction, Heart Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 1991
- Study completion
- Aug 2004 (actual)
- First posted
- 26 May 2000 (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.
In the first phase, to establish the relationship of progression of peripheral vascular disease (PVD) to plasma homocysteine. In the second phase, to conduct a randomized, controlled trial of folic acid treatment of plasma homocysteine in peripheral vascular disease.
Detailed description
BACKGROUND:
Few studies of progression of atherosclerotic peripheral vascular disease have been performed and none have used objective methods to evaluate disease progression in a large number of symptomatic subjects. The study is of obvious major clinical importance. Elevated plasma homocysteine is well established as an independent risk factor for atherosclerosis. If folate treatment results in less frequent/rapid progression of peripheral vascular disease, then it will be confirmed as the first effective treatment for atherosclerosis which is without toxic side effects and does not involve major changes in life/dietary habits.
DESIGN NARRATIVE:
The Homocysteine and Progression of Atherosclerosis Study (HPAS) is a long term, prospective, blinded, multifactoral clinical study which began in 1991 to study the relationship between elevated plasma homocysteine (HC) as well as a number of other risk factors and PVD progression. The study is divided into two phases, conducted sequentially upon 400 patients with symptomatic lower extremity (LED) and cerebrovascular disease (CVD). The first phase was a three year natural history study in which relationship of progression of peripheral vascular disease to plasma homocysteine and other risk factors was established. The clinical question addressed by the natural history study was: Do patients with symptomatic peripheral vascular disease and elevated plasma homocysteine have more rapid/frequent progression of peripheral vascular disease than patients with symptomatic peripheral vascular disease and normal plasma homocysteine? Progression of disease was assessed by the primary outcome variables of ankle brachial pressure index and degree of carotid artery stenosis, as determined in the noninvasive vascular laboratory, and by secondary outcome variables including vascular death, need for vascular surgery, stroke, myocardial infarction, amputation, and other clinical events. All outcome variables were determined by investigators blinded to the results of plasma homocysteine testing.
The second phase of the study, which began in August, 1995, is a blinded, prospective, randomized, placebo-controlled trial of folic acid treatment of elevated plasma homocysteine in the same patient population. Folic acid treatment has been demonstrated to result in normalization of elevated plasma homocysteine. The treatment trial addresses the clinical question: Do patients with symptomatic peripheral vascular disease and elevated plasma homocysteine treated with folate have less frequent/rapid progression of peripheral vascular disease than patients with symptomatic peripheral vascular disease and elevated plasma homocysteine treated with placebo? Although the second phase is described as a clinical trial, the Surgery and Bioengineering Study Section describes it as clinical research, not an NIH-defined Phase III trial.
The study was renewed in FY 1999 through 2003 to continue follow-up and analysis.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study design
- Time perspective
- Retrospective
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 18 Feb 2016.
- Background: PubMed 9474082McLafferty RB, Moneta GL, Passman MA, Brant BM, Taylor LM Jr, Porter JM. Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg. 1998 Jan;27(1):50-6; discussion 56-7. doi: 10.1016/s0741-5214(98)70291-5.
- Background: PubMed 9423939Nehler MR, Taylor LM Jr, Porter JM. Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Surg. 1997 Dec;5(6):559-67. doi: 10.1177/096721099700500603.
- Background: PubMed 9052563Abou-Zamzam AM Jr, Lee RW, Moneta GL, Taylor LM Jr, Porter JM. Functional outcome after infrainguinal bypass for limb salvage. J Vasc Surg. 1997 Feb;25(2):287-95; discussion 295-7. doi: 10.1016/s0741-5214(97)70350-1.
- Background: PubMed 8911401Lee RW, Taylor LM Jr, Landry GJ, Goodnight SH, Moneta GL, Edwards JM, Yeager RA, Porter JM. Prospective comparison of infrainguinal bypass grafting in patients with and without antiphospholipid antibodies. J Vasc Surg. 1996 Oct;24(4):524-31; discussion 531-3. doi: 10.1016/s0741-5214(96)70068-x.
- Background: PubMed 7563406McLafferty RB, Moneta GL, Masser PA, Taylor LM Jr, Porter JM. Progression of atherosclerosis in arteries distal to lower extremity revascularizations. J Vasc Surg. 1995 Oct;22(4):450-5; discussion 455-6. doi: 10.1016/s0741-5214(95)70014-5.
- Background: PubMed 9267266McLafferty RB, Moneta GL, Taylor LM Jr, Porter JM. Ability of ankle-brachial index to detect lower-extremity atherosclerotic disease progression. Arch Surg. 1997 Aug;132(8):836-40; discussion 840-1. doi: 10.1001/archsurg.1997.01430320038005.
- Background: PubMed 8989110Deloughery TG, Evans A, Sadeghi A, McWilliams J, Henner WD, Taylor LM Jr, Press RD. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease. Circulation. 1996 Dec 15;94(12):3074-8. doi: 10.1161/01.cir.94.12.3074.
- Background: PubMed 8911406Nehler MR, Moneta GL, Lee RW, Edwards JM, Taylor LM Jr, Porter JM. Improving selection of patients with less than 60% asymptomatic internal carotid artery stenosis for follow-up carotid artery duplex scanning. J Vasc Surg. 1996 Oct;24(4):580-5; discussion 585-7. doi: 10.1016/s0741-5214(96)70073-3.
- Background: PubMed 7944799Masser PA, Taylor LM Jr, Porter JM. Importance of elevated plasma homocysteine levels as a risk factor for atherosclerosis. Ann Thorac Surg. 1994 Oct;58(4):1240-6. doi: 10.1016/0003-4975(94)90522-3.
- Background: PubMed 7944664Taylor LM Jr, Chitwood RW, Dalman RL, Sexton G, Goodnight SH, Porter JM. Antiphospholipid antibodies in vascular surgery patients. A cross-sectional study. Ann Surg. 1994 Oct;220(4):544-50; discussion 550-1. doi: 10.1097/00000658-199410000-00012.
- Background: PubMed 7933253Taylor LM Jr, Park TC, Edwards JM, Yeager RA, McConnell DC, Moneta GA, Porter JM. Acute disruption of polytetrafluoroethylene grafts adjacent to axillary anastomoses: a complication of axillofemoral grafting. J Vasc Surg. 1994 Oct;20(4):520-6; discussion 526-8. doi: 10.1016/0741-5214(94)90276-3.
- Background: PubMed 8087981Jacobsen DW, Gatautis VJ, Green R, Robinson K, Savon SR, Secic M, Ji J, Otto JM, Taylor LM Jr. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem. 1994 Jun;40(6):873-81.
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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.
Lloyd Taylor
Oregon Health and Science University
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Peripheral Vascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 18 Feb 2016. 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 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005338, which also lists 21 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 18 Feb 2016.