Varicose VeinsPAVEDINCT04436549
Pathology, Venous Disease, and Clinical Correlations
An observational study of Varicose Veins and Pathology, run by University of Catanzaro at 2 sites in Italy.
Trial summary
Chronic Venous Disease (CVD) has a high prevalence in the general population of the western world. Varicose veins are the main signs of this disease that are characterized by important pathological vessel wall changes. There are also several symptoms that affect the quality of life of affected patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Varicose Veins, Pathology, Symptoms and Signs
- What is being tested?
- Stab Avulsion of varicose veins and Histopathologic evaluation of varicose veins
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Dec 2019to 1 Oct 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with varicose veins that are scheduled to undergo surgery for varicose veins removal.
Who may be able to join
- Patients with varicose veins scheduled for surgery
Who cannot join
- Peripheral artery disease
- Malignancy
Trial locations and contacts
2 sites in 1 country.
Italy2 sites, 2 recruiting
- Recruiting
CIFL- Interuniversity Center of Phlebolymphology
Catanzaro, 88100
Raffaele Serra, MD, +393387078043, rserra@unicz.it
- Recruiting
University Magna Graecia of Catanzaro
Catanzaro, 88100
Raffaele Serra, M.D., Ph.D., +3909613647380, rserra@unicz.it
About this study
Official title: Clinical and Pathological Correlations in Chronic Venous Disease
Chronic Venous Disease (CVD) has a high prevalence in the general population of the western world. Varicose veins are the main signs of this disease that are characterized by important pathological vessel wall changes. There are also several symptoms that affect the quality of life of affected patients. The aim of this study is to correlate the main histopathological abnormalities with the type and the intensity of the symptoms.
Read the detailed description
Chronic Venous Disease (CVD) of the lower limbs is a widespread chronic condition of the western world. There are several signs and symptoms that affect quality of life of patients with CVD. One of the main signs of this disease are varicose veins that are enlarged, swollen, and twisting superficial veins. Vessel wall of varicose veins shows a significant histopathological phenotype, characterized by a distortion of structural architecture: endothelial damage, disorganization of muscle bundles and alteration of the composition of the extracellular matrix (ECM). Symptoms may be different, according to disease state, progression and local inflammatory processes. To date, there is no study that correlate the type and the intensity of symptoms with histopathological phenotype.
Aim of this study is to correlate histopathological phenotype with clinical manifestations.
A cohort of patients with varicose veins scheduled for open surgical treatment that will undergo to stab avulsion of varicose veins will be recruited. Subsequently, venous tissue from stab avulsion will collected in order to evaluate the following biomarkers: VEGF (Vascular -Endothelial Growth Factor), PGP 9.5 (Protein Gene Product 9.5), Fibronectin and Matrix Metalloproteinase- 9 (MMP-9).
VEGF has a key role as a regulator of angiogenesis; its expression is highly regulated by hypoxia, in this case induced by venous hypertension. In addition to being a marker of neoangiogenesis, it increases vascular permeability in inflammatory disorders. PGP 9.5 is a marker of the innervation of the vessel wall that plays an important role in the regulation of venous tone. Fibronectin and MMP-9 are direct markers of ECM remodeling and impairment and they have also a role in chronic inflammation.
- Conditions
- Varicose Veins, Pathology, Symptoms and Signs
- Being tested
- Stab Avulsion of varicose veins, Histopathologic evaluation of varicose veins
- Keywords
- pathology, varicose veins, chronic venous disease, symptoms
- Medical subject headings
- Varicose Veins, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stab Avulsion of varicose veinsProcedure or surgery
Also called Phlebectomy
Stab avulsion is a technique to remove varicose veins. In this procedure, several tiny cuts (incisions) are made in the skin through which the varicosed vein is removed. Removed varicose veins will be collected and analyzed.
Histopathologic evaluation of varicose veinsDiagnostic test
Sample obtained from varicose veins of lower limbs of patients will be collected and immediately fixed in formalin. The tissue fragments will be taken from varicose veins. Subsequently the tissue will be embedded in paraffin and 3-to-4 mm thick sections will be prepared by a microtome. The tissue sections will be processed for histological and immunohistochemical studies of VEGF, MM9, PGP 9.5 AND FRIBRONECTIN. For antibodies the EnVision staining system (Dako EnVision™) will be used. For the analysis of the positive structures detected by immunohistochemistry, a semiquantitative evaluation method will be used.
| Study group | Role | What they receive |
|---|---|---|
| Patients with varicose veins | Patients with varicose veins and eligible to receive open surgery (stab avulsion of varicose veins) as routinely care. Receives: Procedure: Stab Avulsion of varicose veins; Diagnostic Test: Histopathologic evaluation of varicose veins |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of Matrix Metalloproteinase-9 (MMP-9)
EnVision staining system (Dako EnVision™) will be used. A synthetic peptide from the middle region of human MMP9 will be used with dilutions 1:50 with Ethylenediaminetetraacetic acid (EDTA).
Measured: at 10 month
Expression of Vascular Endothelial Growth Factor (VEGF)
EnVision staining system (Dako EnVision™) will be used. Monoclonal mouse Anti-Human vascular endothelial growth factor, code No. M7273 will be used with dilution 1:50 with Ethylenediaminetetraacetic acid (EDTA).
Measured: at 10 month
Expression of Fibronectin
EnVision staining system (Dako EnVision™) will be used. A synthetic peptide made toward the C-terminal region of the human Fibronectin protein (within residues 2250-2300) will be used with dilution 1:400 citrate buffer.
Measured: at 10 month
Expression of Protein Gene Product 9.5 (PGP 9.5)
EnVision staining system (Dako EnVision™) will be used. Purified PGP 9.5 isolated from bovine brain will be used with dilution 1:200 citrate buffer
Measured: at 10 month
Secondary outcomes (1)
Correlation of the biomarkers expression with signs and symptoms
The expression of the biomarkers that will be studied on venous tissue samples will be correlated with the type of signs and symptoms complained by the patients.
Measured: At 11 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start1 Dec 2019
- Primary completion1 Sep 2020 (estimated)
- Study completion1 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Varicose VeinsStudies 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
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Catanzaro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Raffaele Serra, MD, Ph.D., University of Catanzaro
- Investigators
- Raffaele Serra, M.D., Ph.D., Principal investigator, University Magna Graecia of Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04436549
- Sponsor's protocol ID
- ER.ALL.2018.11
- Acronym
- PAVEDI
- Status last verified
- Jun 2020
- First submitted
- 15 Jun 2020
- Last updated
- 18 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Birdina J, Pilmane M, Ligers A. The Morphofunctional Changes in the Wall of Varicose Veins. Ann Vasc Surg. 2017 Jul;42:274-284. doi: 10.1016/j.avsg.2016.10.064. Epub 2017 Mar 11.
PubMed 28300675Kucukguven A, Khalil RA. Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins. Curr Drug Targets. 2013 Mar;14(3):287-324.
PubMed 23316963Kolano P, Bednarski IA, Lesiak A, Skibinska M, Stasikowska-Kanicka O, Danilewicz M, Narbutt J. Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations. Postepy Dermatol Alergol. 2020 Apr;37(2):234-239. doi: 10.5114/ada.2020.94840. Epub 2020 May 6.
PubMed 32489360
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Pathological Correlations in Chronic Venous Disease
- ClinicalTrials.gov ID
- NCT04436549
- Acronym / sponsor ID
- PAVEDI / ER.ALL.2018.11
- Conditions
- Varicose Veins, Pathology, Symptoms and Signs
- Keywords
- pathology, varicose veins, chronic venous disease, symptoms
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of CatanzaroUniversity, hospital or other
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 1 Sep 2020 (estimated)
- Study completion
- 1 Oct 2020 (estimated)
- First posted
- 18 Jun 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.
Chronic Venous Disease (CVD) has a high prevalence in the general population of the western world. Varicose veins are the main signs of this disease that are characterized by important pathological vessel wall changes. There are also several symptoms that affect the quality of life of affected patients. The aim of this study is to correlate the main histopathological abnormalities with the type and the intensity of the symptoms.
Detailed description
Chronic Venous Disease (CVD) of the lower limbs is a widespread chronic condition of the western world. There are several signs and symptoms that affect quality of life of patients with CVD. One of the main signs of this disease are varicose veins that are enlarged, swollen, and twisting superficial veins. Vessel wall of varicose veins shows a significant histopathological phenotype, characterized by a distortion of structural architecture: endothelial damage, disorganization of muscle bundles and alteration of the composition of the extracellular matrix (ECM). Symptoms may be different, according to disease state, progression and local inflammatory processes. To date, there is no study that correlate the type and the intensity of symptoms with histopathological phenotype.
Aim of this study is to correlate histopathological phenotype with clinical manifestations.
A cohort of patients with varicose veins scheduled for open surgical treatment that will undergo to stab avulsion of varicose veins will be recruited. Subsequently, venous tissue from stab avulsion will collected in order to evaluate the following biomarkers: VEGF (Vascular -Endothelial Growth Factor), PGP 9.5 (Protein Gene Product 9.5), Fibronectin and Matrix Metalloproteinase- 9 (MMP-9).
VEGF has a key role as a regulator of angiogenesis; its expression is highly regulated by hypoxia, in this case induced by venous hypertension. In addition to being a marker of neoangiogenesis, it increases vascular permeability in inflammatory disorders. PGP 9.5 is a marker of the innervation of the vessel wall that plays an important role in the regulation of venous tone. Fibronectin and MMP-9 are direct markers of ECM remodeling and impairment and they have also a role in chronic inflammation.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with varicose veins | – | Procedure: Stab Avulsion of varicose veins, Diagnostic Test: Histopathologic evaluation of varicose veinsPatients with varicose veins and eligible to receive open surgery (stab avulsion of varicose veins) as routinely care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with varicose veins that are scheduled to undergo surgery for varicose veins removal.
Key inclusion criteria (1 listed)
- Patients with varicose veins scheduled for surgery
Key exclusion criteria (2 listed)
- Peripheral artery disease
- Malignancy
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 |
|---|---|---|
| Stab Avulsion of varicose veinsAlso: PhlebectomyStab avulsion is a technique to remove varicose veins. In this procedure, several tiny cuts (incisions) are made in the skin through which the varicosed vein is removed. Removed varicose veins will be collected and analyzed. | Procedure or surgery | Patients with varicose veins |
| Histopathologic evaluation of varicose veinsSample obtained from varicose veins of lower limbs of patients will be collected and immediately fixed in formalin. The tissue fragments will be taken from varicose veins. Subsequently the tissue will be embedded in paraffin and 3-to-4 mm thick sections will be prepared by a microtome. The tissue sections will be processed for histological and immunohistochemical studies of VEGF, MM9, PGP 9.5 AND FRIBRONECTIN. For antibodies the EnVision staining system (Dako EnVision™) will be used. For the analysis of the positive structures detected by immunohistochemistry, a semiquantitative evaluation method will be used. | Diagnostic test | Patients with varicose veins |
Primary outcome
Expression of Matrix Metalloproteinase-9 (MMP-9)
Time frame: at 10 month
EnVision staining system (Dako EnVision™) will be used. A synthetic peptide from the middle region of human MMP9 will be used with dilutions 1:50 with Ethylenediaminetetraacetic acid (EDTA).
Expression of Vascular Endothelial Growth Factor (VEGF)
Time frame: at 10 month
EnVision staining system (Dako EnVision™) will be used. Monoclonal mouse Anti-Human vascular endothelial growth factor, code No. M7273 will be used with dilution 1:50 with Ethylenediaminetetraacetic acid (EDTA).
Expression of Fibronectin
Time frame: at 10 month
EnVision staining system (Dako EnVision™) will be used. A synthetic peptide made toward the C-terminal region of the human Fibronectin protein (within residues 2250-2300) will be used with dilution 1:400 citrate buffer.
Expression of Protein Gene Product 9.5 (PGP 9.5)
Time frame: at 10 month
EnVision staining system (Dako EnVision™) will be used. Purified PGP 9.5 isolated from bovine brain will be used with dilution 1:200 citrate buffer
1 secondary outcome
Correlation of the biomarkers expression with signs and symptoms
Time frame: At 11 month.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2020.
- Background: PubMed 28300675Birdina J, Pilmane M, Ligers A. The Morphofunctional Changes in the Wall of Varicose Veins. Ann Vasc Surg. 2017 Jul;42:274-284. doi: 10.1016/j.avsg.2016.10.064. Epub 2017 Mar 11.
- Background: PubMed 23316963Kucukguven A, Khalil RA. Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins. Curr Drug Targets. 2013 Mar;14(3):287-324.
- Background: PubMed 32489360Kolano P, Bednarski IA, Lesiak A, Skibinska M, Stasikowska-Kanicka O, Danilewicz M, Narbutt J. Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations. Postepy Dermatol Alergol. 2020 Apr;37(2):234-239. doi: 10.5114/ada.2020.94840. Epub 2020 May 6.
- 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.
Raffaele Serra, M.D., Ph.D. principal investigator
University Magna Graecia of Catanzaro
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Varicose Veins and Pathology, run by University of Catanzaro at 2 sites in Italy.
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 2 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: status not confirmed, as of the sponsor's last update on 18 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raffaele Serra, M.D., Ph.D. (+3909613647380, rserra@unicz.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expression of Matrix Metalloproteinase-9 (MMP-9) (time frame: at 10 month). The study lists 4 primary outcomes in all. 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 NCT04436549, which also lists 3 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 Jun 2020.