Venous DiseaseNCT04138134
Autophagy and Venous Endothelial Function
An observational study of Venous Disease, run by Neuromed IRCCS at 1 site in Italy.
Trial summary
The molecular mechanisms involved in venous endothelial dysfunction are largely unknowns. Autophagy is an intracellular mechanism devoted to the removal of damaged cytoplasmic elements. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Venous Disease
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2022to 1 Apr 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 18 to 85 years
- All sexes
- Adult, Older adult
Study population: * Subjects affected by chronic venous insufficiency or varicose veins undergoing surgical procedure of saphenectomy. * Patients with atherosclerotic obstructive disease of the lower limbs subjected revascularization through implantation of venous by-pass.
Who may be able to join
- Eligible subjects undergoing saphenectomy
- Patients with chronic venous insufficiency
- Patients with varicose veins
- Eligible subjects undergoing peripheral artery revascularization through implantation of venous by-pass derived from saphenous vein
- Acceptance and signature of the informed consent
Who cannot join
- Chronic and acute Inflammatory diseases
- Immunological and rheumatic diseases
- Pre-existing or ongoing neoplasms
- Infectious diseases
- Previous organ transplantation
- Treatment with pharmacological therapies able to modulate autophagy, i. e. rapamycin and derivative compounds (rapalogues).
- Antioxidant therapies in the last three months
- Patients with surgical technical complications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Reactivation of Autophagy Through Spermidine on Venous Endothelial Function
The molecular mechanisms involved in venous endothelial dysfunction are largely unknowns. Autophagy is an intracellular mechanism devoted to the removal of damaged cytoplasmic elements. Previous evidence demonstrated that activation of autophagy exerts beneficial effects in the cardiovascular system, reducing cardiac damage and improving cardiac function in response to stress. However, the association between venous endothelial dysfunction and autophagy remains to be characterized. In this study the investigators will test whether reactivation of autophagy through a natural compound (spermidine) is able to improve vascular function in saphenous veins derived from patients subjected to saphenectomy. The same outcome will be evaluated in saphenous veins isolated from patients with atherosclerotic obstructive disease of the lower limbs subjected revascularization through implantation of venous by-pass.
Read the detailed description
Endothelial dysfunction contributes to different cardiovascular diseases, such as atherosclerosis, myocardial infarction, stroke and peripheral artery diseases. Recent evidence also demonstrated that endothelial dysfunction is associated with vascular venous diseases. In this regard, venous endothelial dysfunction contributes to the development of varicose veins and deep vein thrombosis. Disequilibrium in endothelial function is also present in venous traits derived from saphenous veins which are routinely used as aortocoronary by-pass. The molecular mechanisms involved in venous diseases require further investigations. Autophagy, the intracellular mechanism devoted to the removal of dysfunctional or senescent cytoplasmic elements may represent a new therapeutic target for the treatment of vascular diseases. In this regard, it has been demonstrated that the enhancement of autophagy limits cardiac injury in pre-clinical models of cardiovascular diseases. However, the association between autophagy and vascular disease is still unknown in humans. Spermidine is a natural activator of autophagy which has been demonstrated to extend lifespan in mice and to reduce cardiac dysfunction through autophagy-dependent mechanisms. The objectives of this study will be the following: 1) to test whether spermidine is able to improve vascular function and to reduce oxidative stress in saphenous veins obtained from patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins; 2) to test whether spermidine is able to improve vascular function in saphenous veins derived from patients with atherosclerotic obstructive disease of lower limbs subjected to revascularization through implantation of arteriosus by-pass. In a different set of experiments, the investigators will also test whether vein portions incubated with spermidine show increased autophagy and decreased markers of oxidative stress with respect to controls. The investigators expect that venous segments treated with spermidine will show an amelioration of endothelial function
- Conditions
- Venous Disease
- Keywords
- autophagy, spermidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins | |
| Group 2 | Patients with atherosclerotic obstructive disease of lower limbs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of endothelial function in venous samples from patients with venous insufficiency before and after treatment with autophagy enhancer spermidine
Ex vivo vascular reactivity experiments performed on isolated veins treated or not with spermidine ex vivo.
Measured: Immediately after the sampling
Secondary outcomes (2)
Impact of autophagy on endothelial venous function
Quantification by immunoblot of markers of autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1) and its statistical correlation with venous endothelial function
Measured: 6 months
Correlation between autophagy, oxidative stress and endothelial function
Quantification by immunoblot of markers of autophagy and oxidative stress and statistical correlation with venous endothelial function
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start1 Feb 2022
- Primary completion1 Dec 2022
- Study completion1 Apr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Venous 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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neuromed IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Principal investigator: Giacomo Frati, Co-investigator: Francesco Pompeo
- Responsible party
- Principal investigator, Maurizio Forte, Neuromed IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04138134
- Sponsor's protocol ID
- 9-2019
- Status last verified
- Feb 2023
- First submitted
- 22 Oct 2019
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Reactivation of Autophagy Through Spermidine on Venous Endothelial Function
- ClinicalTrials.gov ID
- NCT04138134
- Acronym / sponsor ID
- 9-2019
- Conditions
- Venous Disease
- Keywords
- autophagy, spermidine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Neuromed IRCCSUniversity, hospital or other
- Collaborators
- Principal investigator: Giacomo Frati, Co-investigator: Francesco Pompeo
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Apr 2023 (estimated)
- First posted
- 24 Oct 2019 (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.
The molecular mechanisms involved in venous endothelial dysfunction are largely unknowns. Autophagy is an intracellular mechanism devoted to the removal of damaged cytoplasmic elements. Previous evidence demonstrated that activation of autophagy exerts beneficial effects in the cardiovascular system, reducing cardiac damage and improving cardiac function in response to stress. However, the association between venous endothelial dysfunction and autophagy remains to be characterized. In this study the investigators will test whether reactivation of autophagy through a natural compound (spermidine) is able to improve vascular function in saphenous veins derived from patients subjected to saphenectomy. The same outcome will be evaluated in saphenous veins isolated from patients with atherosclerotic obstructive disease of the lower limbs subjected revascularization through implantation of venous by-pass.
Detailed description
Endothelial dysfunction contributes to different cardiovascular diseases, such as atherosclerosis, myocardial infarction, stroke and peripheral artery diseases. Recent evidence also demonstrated that endothelial dysfunction is associated with vascular venous diseases. In this regard, venous endothelial dysfunction contributes to the development of varicose veins and deep vein thrombosis. Disequilibrium in endothelial function is also present in venous traits derived from saphenous veins which are routinely used as aortocoronary by-pass. The molecular mechanisms involved in venous diseases require further investigations. Autophagy, the intracellular mechanism devoted to the removal of dysfunctional or senescent cytoplasmic elements may represent a new therapeutic target for the treatment of vascular diseases. In this regard, it has been demonstrated that the enhancement of autophagy limits cardiac injury in pre-clinical models of cardiovascular diseases. However, the association between autophagy and vascular disease is still unknown in humans. Spermidine is a natural activator of autophagy which has been demonstrated to extend lifespan in mice and to reduce cardiac dysfunction through autophagy-dependent mechanisms. The objectives of this study will be the following: 1) to test whether spermidine is able to improve vascular function and to reduce oxidative stress in saphenous veins obtained from patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins; 2) to test whether spermidine is able to improve vascular function in saphenous veins derived from patients with atherosclerotic obstructive disease of lower limbs subjected to revascularization through implantation of arteriosus by-pass. In a different set of experiments, the investigators will also test whether vein portions incubated with spermidine show increased autophagy and decreased markers of oxidative stress with respect to controls. The investigators expect that venous segments treated with spermidine will show an amelioration of endothelial function
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Patients subjected to saphenectomy due to chronic venous insufficiency or varicose veins |
| Group 2 | – | –Patients with atherosclerotic obstructive disease of lower limbs |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- * Subjects affected by chronic venous insufficiency or varicose veins undergoing surgical procedure of saphenectomy. * Patients with atherosclerotic obstructive disease of the lower limbs subjected revascularization through implantation of venous by-pass.
Key inclusion criteria (5 listed)
- Eligible subjects undergoing saphenectomy
- Patients with chronic venous insufficiency
- Patients with varicose veins
- Eligible subjects undergoing peripheral artery revascularization through implantation of venous by-pass derived from saphenous vein
- Acceptance and signature of the informed consent
Key exclusion criteria (8 listed)
- Chronic and acute Inflammatory diseases
- Immunological and rheumatic diseases
- Pre-existing or ongoing neoplasms
- Infectious diseases
- Previous organ transplantation
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
Evaluation of endothelial function in venous samples from patients with venous insufficiency before and after treatment with autophagy enhancer spermidine
Time frame: Immediately after the sampling
Ex vivo vascular reactivity experiments performed on isolated veins treated or not with spermidine ex vivo.
2 secondary outcomes
Impact of autophagy on endothelial venous function
Time frame: 6 months
Correlation between autophagy, oxidative stress and endothelial function
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Venous Disease, run by Neuromed IRCCS 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 5 inclusion and 8 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 8 Feb 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 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?
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?
Evaluation of endothelial function in venous samples from patients with venous insufficiency before and after treatment with autophagy enhancer spermidine (time frame: Immediately after the sampling). 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 8 Feb 2023.