- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04138134
Autophagy and Venous Endothelial Function
February 4, 2023 updated by: Maurizio Forte, Neuromed IRCCS
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.
Study Overview
Status
Active, not recruiting
Conditions
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 Type
Observational
Enrollment (Anticipated)
200
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Isernia
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Pozzilli, Isernia, Italy
- IRCCS Neuromed
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 85 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
N/A
Genders Eligible for Study
All
Sampling Method
Probability Sample
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.
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
---|
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 the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Immediately after the sampling
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Impact of autophagy on endothelial venous function
Time Frame: 6 months
|
Quantification by immunoblot of markers of autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1) and its statistical correlation with venous endothelial function
|
6 months
|
Correlation between autophagy, oxidative stress and endothelial function
Time Frame: 6 months
|
Quantification by immunoblot of markers of autophagy and oxidative stress and statistical correlation with venous endothelial function
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
February 1, 2022
Primary Completion (ACTUAL)
December 1, 2022
Study Completion (ANTICIPATED)
April 1, 2023
Study Registration Dates
First Submitted
October 22, 2019
First Submitted That Met QC Criteria
October 22, 2019
First Posted (ACTUAL)
October 24, 2019
Study Record Updates
Last Update Posted (ACTUAL)
February 8, 2023
Last Update Submitted That Met QC Criteria
February 4, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 9-2019
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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