AtherosclerosisNCT04502849
Apoptosis Proteins and Endothelial Dysfunction in Patients With Atherosclerosis of Peripheral Arteries
An observational study of Atherosclerosis and Endothelial Dysfunction, run by Ryazan State Medical University at 1 site in Russia.
Trial summary
Modern vascular surgery has various options for open and endovascular surgical methods aimed at treating patients with peripheral arterial diseases. Despite the achievements of vascular surgery, the occurrence of postoperative complications levels out the success of surgical interventions and requires repeated… Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis, Endothelial Dysfunction
- What is being tested?
- Bypass surgery, Endovascular angioplasty/stenting and Hybrid surgery
- Type of treatment
- Surgery or procedure
- How many people
- 250 participants
- Where
- 1 siteRussia
- Study dates
- 1 Jan 2020to 1 Nov 2023
- 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 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with atherosclerotic peripheral arterial disease.
Who may be able to join
- men or women over 40 years of age;
- presence of atherosclerotic peripheral artery disease.
Who cannot join
- men or women under 40 years of age;
- chronic lower limb ischemia of a different etiology (disease Burger, aortoarteritis, etc.),
- active cancer or remission period less than 5 years;
- decompensated diabetes mellitus;
- pregnancy or breastfeeding in women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comprehensive Assessment of Indices of Apoptosis and Endothelial Dysfunction and Methods of Their Correction in Patients With Atherosclerosis of Peripheral Arteries
Modern vascular surgery has various options for open and endovascular surgical methods aimed at treating patients with peripheral arterial diseases. Despite the achievements of vascular surgery, the occurrence of postoperative complications levels out the success of surgical interventions and requires repeated surgical interventions. The most common complication is stenosis of the reconstruction zone, which develops in approximately 50% of operated patients.
At present, the apoptosis system plays an equally important role in the development of restenosis of the intervention zone. It has been recognized as a central component in the pathogenesis of atherosclerosis, in which the Bcl-2 family of proteins is activated. It is a group of cellular proteins that are important regulators of the apoptosis system in cells located in the mitochondrial membrane. In experimental animal models, it was shown that apoptosis after angioplasty of the coronary arteries proceeds in the form of two waves. After injury to the vascular wall, during the first hours, it is activated in the smooth muscle cells (SMC) of media, and after two weeks in the cells of the neointima, by the 28th day it almost completely stops. A decrease in the apoptosis index in the postoperative period may cause the development of restenosis of the reconstruction zone. The use of antioxidants, for example, alpha-tocopherol acetate, in the first month of the postoperative period, at the time of activation of apoptosis, inhibits the latter and reduces the proliferative activity of the SMC media and neointima. One month after surgery, delayed apoptosis of vascular wall cells can lead to the development of neointima and restenosis. In this case, the use of drugs that enhance apoptosis, for example, lipophilic statins, calcium channel blockers, will be relevant.
Nitric oxide metabolites, depending on the concentration, can act as both an inducer and an inhibitor of apoptosis. The mechanism of NO-induced apoptosis in SMC includes an increase in the Bax / Bcl-2 expression ratio, which leads to the release of cytochrome C from mitochondria, activation of caspase-3 and -9. In patients with atherosclerosis of the peripheral arteries, proteins of the Bcl-2 family and their relationship with markers of endothelial dysfunction have not been sufficiently studied, the results obtained are contradictory.
Read the detailed description
250 patients will be divided into 5 groups with follow-up period of 2 years. Blood sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB (platelet derived growth factor BB), VEGF (vascular endothelial growth factor) and endothelial dysfunction (NO metabolites) markers will be performed before,1 day after, 1 and 6 month after surgery for groups A-C and for groups D, E when included into study.
Arterial wall sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB, VEGF) during surgery in group A-C patients.
Duplex ultrasound of lower limbs arteries will be performed before,1, 6, 12, 18 and 24 month after surgery for groups A-D and for group E when included into study.
100 mg per os of Vitamin E 1 per day during 1 month after surgery will be prescribed to half of groups A-C patients.
- Conditions
- Atherosclerosis, Endothelial Dysfunction
- Being tested
- Bypass surgery, Endovascular angioplasty/stenting, Hybrid surgery, Vitamin E, Duplex ultrasound
- Keywords
- atherosclerosis, endothelial dysfunction, apoptosis, restenosis, atherosclerotic plaque
- Medical subject headings
- Atherosclerosis, Plaque, Atherosclerotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bypass surgeryProcedure or surgery
Creating a bypass with graft or vein.
Endovascular angioplasty/stentingProcedure or surgery
Performing an angioplasty with or without stenting in stenosis.
Hybrid surgeryProcedure or surgery
Performing an angioplasty with or without stenting in stenosis and creating a bypass with graft or vein.
Vitamin EDrug
Also called Tocopherol acetate
100 mg Vitamin E per os 1 per day (1 month).
Duplex ultrasoundDiagnostic test
Duplex ultrasound of lower limbs arteries.
Blood samplingDiagnostic test
Blood sampling for apoptosis and endothelial dysfunction markers.
Arterial wall samplingDiagnostic test
Arterial wall sampling for apoptosis markers.
| Study group | Role | What they receive |
|---|---|---|
| Group "Bypass" (A) | 50 patients with indications for bypass surgery (chronic lower limb ischemia, stage 2b-4 Fontaine). Receives: Procedure: Bypass surgery; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling; Diagnostic Test: Arterial wall sampling | |
| Group "Endovascular" (B) | 50 patients with indications for endovascular angioplasty and stenting (chronic lower limb ischemia, stage 2b-4 Fontaine). Receives: Procedure: Endovascular angioplasty/stenting; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling | |
| Group "Hybrid" (C) | 50 patients with indications for hybrid surgery (endovascular angioplasty/stenting and bypass surgery; chronic lower limb ischemia, stage 2b-4 Fontaine). Receives: Procedure: Hybrid surgery; Drug: Vitamin E; Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling; Diagnostic Test: Arterial wall sampling | |
| Group "Conservative" (D) | 50 patients without indications surgery (conservative treatment, chronic lower limb ischemia, stage 2b-4 Fontaine). Receives: Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling | |
| Group "Healthy volunteers" (E) | 50 healthy subjects. Receives: Diagnostic Test: Duplex ultrasound; Diagnostic Test: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Restenosis of the reconstruction zone after surgery (detection of narrowing of the lumen of an artery or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Revealing restenosis after surgery.
Measured: Up to 2 years after enrollment.
Thrombosis of the reconstruction zone after surgery (detection of thrombosis in arteries or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Revealing thrombosis after surgery.
Measured: Up to 2 years after enrollment.
Progression of atherosclerosis (detection of narrowing of the lumen of an arteries by atherosclerotic plaque using instrumental methods (ultrasound, angiography)).
Increasing the stage of atherosclerosis (Fontaine classification).
Measured: Up to 2 years after enrollment.
Secondary outcomes (2)
Deviations of apoptosis markers in blood and tissue homogenate (Bcl-2, Bax, Fas, VEGF, P53, PDGF-BB) from reference values.
Deviation of apoptosis markers from reference values.
Measured: Up to 2 years after enrollment.
Deviations of endothelial dysfunction markers in blood (NO metabolites) from reference values..
Deviation of endothelial dysfunction markers from reference values.
Measured: Up to 2 years after enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start1 Jan 2020
- Primary completion1 Jan 2023
- Study completion1 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ryazan State Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Igor A Suchkov, Sc.D., Principal investigator, Ryazan State Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04502849
- Sponsor's protocol ID
- 25.07
- Status last verified
- Aug 2022
- First submitted
- 28 Jul 2020
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comprehensive Assessment of Indices of Apoptosis and Endothelial Dysfunction and Methods of Their Correction in Patients With Atherosclerosis of Peripheral Arteries
- ClinicalTrials.gov ID
- NCT04502849
- Acronym / sponsor ID
- 25.07
- Conditions
- Atherosclerosis, Endothelial Dysfunction
- Keywords
- atherosclerosis, endothelial dysfunction, apoptosis, restenosis, atherosclerotic plaque
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Ryazan State Medical UniversityUniversity, hospital or other
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 6 Aug 2020 (actual)
- 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.
Modern vascular surgery has various options for open and endovascular surgical methods aimed at treating patients with peripheral arterial diseases. Despite the achievements of vascular surgery, the occurrence of postoperative complications levels out the success of surgical interventions and requires repeated surgical interventions. The most common complication is stenosis of the reconstruction zone, which develops in approximately 50% of operated patients.
At present, the apoptosis system plays an equally important role in the development of restenosis of the intervention zone. It has been recognized as a central component in the pathogenesis of atherosclerosis, in which the Bcl-2 family of proteins is activated. It is a group of cellular proteins that are important regulators of the apoptosis system in cells located in the mitochondrial membrane. In experimental animal models, it was shown that apoptosis after angioplasty of the coronary arteries proceeds in the form of two waves. After injury to the vascular wall, during the first hours, it is activated in the smooth muscle cells (SMC) of media, and after two weeks in the cells of the neointima, by the 28th day it almost completely stops. A decrease in the apoptosis index in the postoperative period may cause the development of restenosis of the reconstruction zone. The use of antioxidants, for example, alpha-tocopherol acetate, in the first month of the postoperative period, at the time of activation of apoptosis, inhibits the latter and reduces the proliferative activity of the SMC media and neointima. One month after surgery, delayed apoptosis of vascular wall cells can lead to the development of neointima and restenosis. In this case, the use of drugs that enhance apoptosis, for example, lipophilic statins, calcium channel blockers, will be relevant.
Nitric oxide metabolites, depending on the concentration, can act as both an inducer and an inhibitor of apoptosis. The mechanism of NO-induced apoptosis in SMC includes an increase in the Bax / Bcl-2 expression ratio, which leads to the release of cytochrome C from mitochondria, activation of caspase-3 and -9. In patients with atherosclerosis of the peripheral arteries, proteins of the Bcl-2 family and their relationship with markers of endothelial dysfunction have not been sufficiently studied, the results obtained are contradictory.
Detailed description
250 patients will be divided into 5 groups with follow-up period of 2 years. Blood sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB (platelet derived growth factor BB), VEGF (vascular endothelial growth factor) and endothelial dysfunction (NO metabolites) markers will be performed before,1 day after, 1 and 6 month after surgery for groups A-C and for groups D, E when included into study.
Arterial wall sampling for apoptosis and proliferation (Bcl-2, Bax, Fas, p53, PDGF-BB, VEGF) during surgery in group A-C patients.
Duplex ultrasound of lower limbs arteries will be performed before,1, 6, 12, 18 and 24 month after surgery for groups A-D and for group E when included into study.
100 mg per os of Vitamin E 1 per day during 1 month after surgery will be prescribed to half of groups A-C patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group "Bypass" (A) | – | Procedure: Bypass surgery, Drug: Vitamin E, Diagnostic Test: Duplex ultrasound, Diagnostic Test: Blood sampling, Diagnostic Test: Arterial wall sampling50 patients with indications for bypass surgery (chronic lower limb ischemia, stage 2b-4 Fontaine). |
| Group "Endovascular" (B) | – | Procedure: Endovascular angioplasty/stenting, Drug: Vitamin E, Diagnostic Test: Duplex ultrasound, Diagnostic Test: Blood sampling50 patients with indications for endovascular angioplasty and stenting (chronic lower limb ischemia, stage 2b-4 Fontaine). |
| Group "Hybrid" (C) | – | Procedure: Hybrid surgery, Drug: Vitamin E, Diagnostic Test: Duplex ultrasound, Diagnostic Test: Blood sampling, Diagnostic Test: Arterial wall sampling50 patients with indications for hybrid surgery (endovascular angioplasty/stenting and bypass surgery; chronic lower limb ischemia, stage 2b-4 Fontaine). |
| Group "Conservative" (D) | – | Diagnostic Test: Duplex ultrasound, Diagnostic Test: Blood sampling50 patients without indications surgery (conservative treatment, chronic lower limb ischemia, stage 2b-4 Fontaine). |
| Group "Healthy volunteers" (E) | – | Diagnostic Test: Duplex ultrasound, Diagnostic Test: Blood sampling50 healthy subjects. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with atherosclerotic peripheral arterial disease.
Key inclusion criteria (2 listed)
- men or women over 40 years of age;
- presence of atherosclerotic peripheral artery disease.
Key exclusion criteria (5 listed)
- men or women under 40 years of age;
- chronic lower limb ischemia of a different etiology (disease Burger, aortoarteritis, etc.),
- active cancer or remission period less than 5 years;
- decompensated diabetes mellitus;
- pregnancy or breastfeeding in women
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 |
|---|---|---|
| Bypass surgeryCreating a bypass with graft or vein. | Procedure or surgery | Group "Bypass" (A) |
| Endovascular angioplasty/stentingPerforming an angioplasty with or without stenting in stenosis. | Procedure or surgery | Group "Endovascular" (B) |
| Hybrid surgeryPerforming an angioplasty with or without stenting in stenosis and creating a bypass with graft or vein. | Procedure or surgery | Group "Hybrid" (C) |
| Vitamin EAlso: Tocopherol acetate100 mg Vitamin E per os 1 per day (1 month). | Drug | Group "Bypass" (A), Group "Endovascular" (B), Group "Hybrid" (C) |
| Duplex ultrasoundDuplex ultrasound of lower limbs arteries. | Diagnostic test | Group "Bypass" (A), Group "Conservative" (D), Group "Endovascular" (B), Group "Healthy volunteers" (E), Group "Hybrid" (C) |
| Blood samplingBlood sampling for apoptosis and endothelial dysfunction markers. | Diagnostic test | Group "Bypass" (A), Group "Conservative" (D), Group "Endovascular" (B), Group "Healthy volunteers" (E), Group "Hybrid" (C) |
| Arterial wall samplingArterial wall sampling for apoptosis markers. | Diagnostic test | Group "Bypass" (A), Group "Hybrid" (C) |
Primary outcome
Restenosis of the reconstruction zone after surgery (detection of narrowing of the lumen of an artery or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Time frame: Up to 2 years after enrollment.
Revealing restenosis after surgery.
Thrombosis of the reconstruction zone after surgery (detection of thrombosis in arteries or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)).
Time frame: Up to 2 years after enrollment.
Revealing thrombosis after surgery.
Progression of atherosclerosis (detection of narrowing of the lumen of an arteries by atherosclerotic plaque using instrumental methods (ultrasound, angiography)).
Time frame: Up to 2 years after enrollment.
Increasing the stage of atherosclerosis (Fontaine classification).
2 secondary outcomes
Deviations of apoptosis markers in blood and tissue homogenate (Bcl-2, Bax, Fas, VEGF, P53, PDGF-BB) from reference values.
Time frame: Up to 2 years after enrollment.
Deviations of endothelial dysfunction markers in blood (NO metabolites) from reference values..
Time frame: Up to 2 years after enrollment.
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 Nov 2023.
- Individual participant dataSharing planned: Undecided
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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.
Igor A Suchkov, Sc.D. principal investigator
Ryazan State Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis and Endothelial Dysfunction, run by Ryazan State Medical University at 1 site in Russia.
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 2 inclusion and 5 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 18 Nov 2023. 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 Russia. 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 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?
Restenosis of the reconstruction zone after surgery (detection of narrowing of the lumen of an artery or prosthesis in the reconstruction area using instrumental methods (ultrasound, angiography)). (time frame: Up to 2 years after enrollment.). The study lists 3 primary outcomes in all. 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 18 Nov 2023.