Genetic Predisposition to DiseaseGECVELUSNCT05134597
Gene Expression in Chronic Venous Leg Ulcers
An observational study of Genetic Predisposition to Disease and Inflammation, run by University of Catanzaro at 1 site in Italy.
Trial summary
Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries that may negatively impact the quality of life (QoL) of affected patients. Chronic venous leg ulcers (CVLUs) are the most severe form of CVD, and several genetic and molecular alterations have been studied in order… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Genetic Predisposition to Disease, Inflammation, Venous Leg Ulcer
- What is being tested?
- Genetic assessment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2021to 31 Mar 2022
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with chronic venous disease according to CEAP Classification of Chronic Venous Disorders with clinical classes 2-6.
Who may be able to join
- patients with chronic venous disease with CEAP Clinical classes (C) 2-6: C2: varicose veins C3: edema C4: skin changes C5: healed venous ulcers C6: active venous ulcers
Who cannot join
- patients with peripheral artery disease
- patients with malignancy
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University Magna Graecia of Catanzaro
Catanzaro, 880100
Raffaele Serra, M.D., +3909613647380, rserra@unicz.it
Raffaele Serra, M.D., Ph.D.
About this study
Official title: Th17- Gene Expression Profile in Patients With Chronic Venous Leg Insufficiency and Ulcers: Genetical and Clinical Outcomes
Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries that may negatively impact the quality of life (QoL) of affected patients. Chronic venous leg ulcers (CVLUs) are the most severe form of CVD, and several genetic and molecular alterations have been studied in order to understand the progression of CVD towards CLVUs. Chronic inflammation is a key element in CVLUs onset, and recently T helper 17 (Th-17) cells, a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor, seem to be related to several chronic disease. The aim of this study is to evaluate Th17- Gene Expression profile in patients with CVD and CVLUs.
Read the detailed description
Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries, with a prevalence ranging from 10% in adults younger than 30 years of age to nearly 80% for individuals >70 years of age. CVD clinical manifestations vary from mild clinical signs, including varicose veins, to more advanced and severe signs such as chronic venous leg ulcers (CVLUs) which significantly impact the quality of life (QoL) of affected patients. Several genetic and molecular alterations have been studied so far to understand the onset, progression, and complications of CVD, including Chronic Venous Insufficiency (CVI) states in which CVLUs may develop. The appearance of CVLUs is generally preceded by skin changes of the lower limbs such as lipodermatosclerosis, that is a chronic inflammatory condition due to CVI, characterised by an inflammatory skin condition. This pathological event leads to subcutaneous fibrosis and hardening of the affected skin, resulting in tissue hypoxia essential for venous ulceration.Gene expression profile studies, present in the current literature, allow us to hypothesize several mechanisms underlying the development of CVLU, highlighting a wide variety of genetic-molecular interconnections. Nevertheless, none to date is able to provide a genetic and cellular model linking the pathogenetic events that lead to the onset of CVLU or the progression of these lesions.T helper 17 (Th-17) cells are a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor. The development and differentiation and expansion of Th-17 depends on differentiation factors (TGF- β ), growth factors (IL-23/IL23R) and several transcription factors (ROR-γt, STAT3 ).
Interestingly, the Th-17 axis has been implicated in several autoimmune diseases including rheumatoid arthritis, multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and autoimmune encephalitis among others. In addition, an increasingly strong role of the Th-17 axis in tumor drug resistance and in the progression and radicalization of HIV infection is recently emerging.
Our study aims at evaluation Th17- Gene Expression profile in patients with CVD and CVLUs.
- Being tested
- Genetic assessment
- Medical subject headings
- Genetic Predisposition to Disease, Inflammation, Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic assessmentGenetic
Blood samples will be collected in 3-mL K3 EDTA vacutainer tubes. Peripheral blood mononuclear cells will be isolated via density gradient centrifugation within 2 hours of sample collection. Primary CD4+ T cells will be purified from the peripheral blood lymphocytes using a magnetic cell sorting CD4+ T cell isolation kit, according to the manufacturer's instructions. RNA extraction will be performed. Total RNA will be quantified, and the quality of RNA will be assayed using formaldehyde agarose gel electrophoresis and by determining the 260/280 absorbance ratio. One microgram of total RNA from each sample will be subjected to reverse transcription. One microliter of cDNA will be amplified via real-time PCR and 10 pmol of primers specific to IL23R, IL17, SGK1, RANBP1, TFGB. Real-time PCR assays will be performed in triplicate The specificity of the PCR products will be determined via melting curve analysis.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Patients with Chronic Venous Disease (CVD) | Patients with CVD at different stages, according to CEAP Classification of Chronic Venous Disorders, will be recruited. Receives: Genetic: Genetic assessment | |
| Group 2 - Healthy subjects without Chronic Venous Disease (CVD) | Voluntary healthy subjects without Chronic Venous Disease (CVD) will be recruited. Receives: Genetic: Genetic assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Th17- Gene Expression profile
Genetic profile in patients with Chronic Venous Disease and in Healthy subjects will be evaluated.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study start1 Jan 2021
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Genetic Predisposition to DiseaseStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 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., Study chair, University Magna Graecia of Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05134597
- Sponsor's protocol ID
- E.R.ALL.2018.42
- Acronym
- GECVELUS
- Status last verified
- Nov 2021
- First submitted
- 14 Nov 2021
- Last updated
- 26 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Serra R, Ssempijja L, Provenzano M, Andreucci M. Genetic biomarkers in chronic venous disease. Biomark Med. 2020 Feb;14(2):75-80. doi: 10.2217/bmm-2019-0408. Epub 2020 Feb 13. No abstract available.
PubMed 32053001Metzinger L, de Franciscis S, Serra R. The Management of Cardiovascular Risk through Epigenetic Biomarkers. Biomed Res Int. 2017;2017:9158572. doi: 10.1155/2017/9158572. Epub 2017 Jul 13.
PubMed 28785591de Franciscis S, Metzinger L, Serra R. The Discovery of Novel Genomic, Transcriptomic, and Proteomic Biomarkers in Cardiovascular and Peripheral Vascular Disease: The State of the Art. Biomed Res Int. 2016;2016:7829174. doi: 10.1155/2016/7829174. Epub 2016 May 19.
PubMed 27298828Serra R, Buffone G, de Franciscis A, Mastrangelo D, Molinari V, Montemurro R, de Franciscis S. A genetic study of chronic venous insufficiency. Ann Vasc Surg. 2012 Jul;26(5):636-42. doi: 10.1016/j.avsg.2011.11.036.
PubMed 22664280Kim JS, Jordan MS. Diversity of IL-17-producing T lymphocytes. Cell Mol Life Sci. 2013 Jul;70(13):2271-90. doi: 10.1007/s00018-012-1163-6. Epub 2012 Oct 4.
PubMed 23052209Smith PD. Update on chronic-venous-insufficiency-induced inflammatory processes. Angiology. 2001 Aug;52 Suppl 1:S35-42. doi: 10.1177/0003319701052001s05.
PubMed 11510595Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003 Apr;14(2):155-74. doi: 10.1016/s1359-6101(03)00002-9.
PubMed 12651226Amato R, Dattilo V, Brescia C, D'Antona L, Iuliano R, Trapasso F, Perrotti N, Costa D, Ielapi N, Aiello F, Provenzano M, Bracale UM, Andreucci M, Serra R. Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence. Biomolecules. 2022 Jun 28;12(7):902. doi: 10.3390/biom12070902.
PubMed 35883458
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Th17- Gene Expression Profile in Patients With Chronic Venous Leg Insufficiency and Ulcers: Genetical and Clinical Outcomes
- ClinicalTrials.gov ID
- NCT05134597
- Acronym / sponsor ID
- GECVELUS / E.R.ALL.2018.42
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CatanzaroUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 26 Nov 2021 (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) is a widespread clinical condition widely spread in the western countries that may negatively impact the quality of life (QoL) of affected patients. Chronic venous leg ulcers (CVLUs) are the most severe form of CVD, and several genetic and molecular alterations have been studied in order to understand the progression of CVD towards CLVUs. Chronic inflammation is a key element in CVLUs onset, and recently T helper 17 (Th-17) cells, a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor, seem to be related to several chronic disease. The aim of this study is to evaluate Th17- Gene Expression profile in patients with CVD and CVLUs.
Detailed description
Chronic Venous Disease (CVD) is a widespread clinical condition widely spread in the western countries, with a prevalence ranging from 10% in adults younger than 30 years of age to nearly 80% for individuals >70 years of age. CVD clinical manifestations vary from mild clinical signs, including varicose veins, to more advanced and severe signs such as chronic venous leg ulcers (CVLUs) which significantly impact the quality of life (QoL) of affected patients. Several genetic and molecular alterations have been studied so far to understand the onset, progression, and complications of CVD, including Chronic Venous Insufficiency (CVI) states in which CVLUs may develop. The appearance of CVLUs is generally preceded by skin changes of the lower limbs such as lipodermatosclerosis, that is a chronic inflammatory condition due to CVI, characterised by an inflammatory skin condition. This pathological event leads to subcutaneous fibrosis and hardening of the affected skin, resulting in tissue hypoxia essential for venous ulceration.Gene expression profile studies, present in the current literature, allow us to hypothesize several mechanisms underlying the development of CVLU, highlighting a wide variety of genetic-molecular interconnections. Nevertheless, none to date is able to provide a genetic and cellular model linking the pathogenetic events that lead to the onset of CVLU or the progression of these lesions.T helper 17 (Th-17) cells are a subtype of pro-inflammatory T helper (CD4+) cells defined by the production of a cytokine signature of which IL-17 represents the progenitor. The development and differentiation and expansion of Th-17 depends on differentiation factors (TGF- β ), growth factors (IL-23/IL23R) and several transcription factors (ROR-γt, STAT3 ).
Interestingly, the Th-17 axis has been implicated in several autoimmune diseases including rheumatoid arthritis, multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and autoimmune encephalitis among others. In addition, an increasingly strong role of the Th-17 axis in tumor drug resistance and in the progression and radicalization of HIV infection is recently emerging.
Our study aims at evaluation Th17- Gene Expression profile in patients with CVD and CVLUs.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Patients with Chronic Venous Disease (CVD) | – | Genetic: Genetic assessmentPatients with CVD at different stages, according to CEAP Classification of Chronic Venous Disorders, will be recruited. |
| Group 2 - Healthy subjects without Chronic Venous Disease (CVD) | – | Genetic: Genetic assessmentVoluntary healthy subjects without Chronic Venous Disease (CVD) will be recruited. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with chronic venous disease according to CEAP Classification of Chronic Venous Disorders with clinical classes 2-6.
Key inclusion criteria (1 listed)
- patients with chronic venous disease with CEAP Clinical classes (C) 2-6: C2: varicose veins C3: edema C4: skin changes C5: healed venous ulcers C6: active venous ulcers
Key exclusion criteria (2 listed)
- patients with peripheral artery disease
- patients with 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 |
|---|---|---|
| Genetic assessmentBlood samples will be collected in 3-mL K3 EDTA vacutainer tubes. Peripheral blood mononuclear cells will be isolated via density gradient centrifugation within 2 hours of sample collection. Primary CD4+ T cells will be purified from the peripheral blood lymphocytes using a magnetic cell sorting CD4+ T cell isolation kit, according to the manufacturer's instructions. RNA extraction will be performed. Total RNA will be quantified, and the quality of RNA will be assayed using formaldehyde agarose gel electrophoresis and by determining the 260/280 absorbance ratio. One microgram of total RNA from each sample will be subjected to reverse transcription. One microliter of cDNA will be amplified via real-time PCR and 10 pmol of primers specific to IL23R, IL17, SGK1, RANBP1, TFGB. Real-time PCR assays will be performed in triplicate The specificity of the PCR products will be determined via melting curve analysis. | Genetic | Group 1 - Patients with Chronic Venous Disease (CVD), Group 2 - Healthy subjects without Chronic Venous Disease (CVD) |
Primary outcome
Th17- Gene Expression profile
Time frame: 1 year
Genetic profile in patients with Chronic Venous Disease and in Healthy subjects will be evaluated.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2021.
- Background: PubMed 32053001Serra R, Ssempijja L, Provenzano M, Andreucci M. Genetic biomarkers in chronic venous disease. Biomark Med. 2020 Feb;14(2):75-80. doi: 10.2217/bmm-2019-0408. Epub 2020 Feb 13. No abstract available.
- Background: PubMed 28785591Metzinger L, de Franciscis S, Serra R. The Management of Cardiovascular Risk through Epigenetic Biomarkers. Biomed Res Int. 2017;2017:9158572. doi: 10.1155/2017/9158572. Epub 2017 Jul 13.
- Background: PubMed 27298828de Franciscis S, Metzinger L, Serra R. The Discovery of Novel Genomic, Transcriptomic, and Proteomic Biomarkers in Cardiovascular and Peripheral Vascular Disease: The State of the Art. Biomed Res Int. 2016;2016:7829174. doi: 10.1155/2016/7829174. Epub 2016 May 19.
- Background: PubMed 22664280Serra R, Buffone G, de Franciscis A, Mastrangelo D, Molinari V, Montemurro R, de Franciscis S. A genetic study of chronic venous insufficiency. Ann Vasc Surg. 2012 Jul;26(5):636-42. doi: 10.1016/j.avsg.2011.11.036.
- Background: PubMed 23052209Kim JS, Jordan MS. Diversity of IL-17-producing T lymphocytes. Cell Mol Life Sci. 2013 Jul;70(13):2271-90. doi: 10.1007/s00018-012-1163-6. Epub 2012 Oct 4.
- Background: PubMed 11510595Smith PD. Update on chronic-venous-insufficiency-induced inflammatory processes. Angiology. 2001 Aug;52 Suppl 1:S35-42. doi: 10.1177/0003319701052001s05.
- Background: PubMed 12651226Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003 Apr;14(2):155-74. doi: 10.1016/s1359-6101(03)00002-9.
- Derived from this study: PubMed 35883458Amato R, Dattilo V, Brescia C, D'Antona L, Iuliano R, Trapasso F, Perrotti N, Costa D, Ielapi N, Aiello F, Provenzano M, Bracale UM, Andreucci M, Serra R. Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence. Biomolecules. 2022 Jun 28;12(7):902. doi: 10.3390/biom12070902.
- 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. study chair
University Magna Graecia of Catanzaro
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 Genetic Predisposition to Disease and Inflammation, run by University of Catanzaro at 1 site 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 26 Nov 2021. 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 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?
Th17- Gene Expression profile (time frame: 1 year). 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 NCT05134597, which also lists 8 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 26 Nov 2021.