- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03211000
Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm
April 8, 2022 updated by: Maurizio Forte, Neuromed IRCCS
Study of the Molecular Mechanisms Associated With the Formation of Human Aortic Aneurysm: a Focus on Autophagy, Oxidative Stress and Hippo Signaling
The molecular mechanisms contributing to the development of aortic aneurysmal disease are poorly characterized making actual therapies not sufficient.
Autophagy is an intracellular mechanism that removes dysfunctional organelles and unfolded proteins, thereby maintaining cellular homeostasis.
Activation of autophagy was shown to limit cardiac damage during stress.
Accordingly, autophagy was found to be inhibited in the heart in animal models of metabolic syndrome, diabetes, obesity and aging thereby contributing to the development of cardiac derangements associated with these conditions.
However, it remains to fully dissect the association between autophagy and structural alterations of the aortic wall and endothelial dysfunction in humans.
In this study the correlation between levels of autophagy and the development of human aortic aneurysm will be assessed in patients subjected to surgical interventions for aortic pathologies.
The association of Hippo signaling activation with the formation of aortic disease will also be evaluated, since previous work demonstrated that the Hippo pathway negatively regulates autophagy and promotes the development of cellular abnormalities.
The results of this study may provide new insights into the mechanisms underlying the development of aortic disease.
Study Overview
Status
Completed
Conditions
Detailed Description
Autophagy may represent a new potential therapeutic target for the prevention and the treatment of aortic pathologies.
It is a cellular self- digestion mechanism that prevents the accumulation of senescent organelles and damaged proteins.
Autophagy plays a pivotal role in the regulation of cellular homeostasis and promotes the cellular response to stress.
However, further investigations are needed to establish how autophagy is influenced by cardiovascular risk factors, as well as by pharmacological therapy.
Moreover, it is still unclear in humans the association between autophagy and structural and functional alterations of aortic wall, as well as its association with endothelial dysfunction, especially in subjects affected by aortic pathologies.
Furthermore, no data are available on the correlation between autophagy and the prognosis of patients who underwent cardio-surgical procedures for aortic pathologies.
In this study, autophagy levels will be evaluated in human aortic aneurysm samples obtained from patients enrolled for a surgical aorta procedures.
Autophagy markers in each aneurysm sample will be compared to those observed in the non-aneurysmatic aortic portion adjacent to the aneurysmatic tract obtained from the same patient.
Levels of autophagy will also be correlated with markers of apoptosis and oxidative stress in both the aneurysmatic and non-aneurysmatic aortic parts.
The involvement of the Hippo signaling pathway and inflammation in control and aneurysm samples will also be investigated.
The investigators expect that autophagy levels will be lower in aneurysm samples with respect to non-aneurysmatic adjacent aortic portions.
They will also be inversely correlated with aneurysm dimension.
In contrast, the Hippo pathway will be activated in aortic aneurysms.
Autophagy and Hippo signaling markers will also be correlated with markers of apoptosis and oxidative stress in aortic samples.
In conclusion, the results of this study may underline the vascular role of autophagy and Hippo signaling and their involvement in the development of aortic diseases.
Study Type
Observational
Enrollment (Actual)
30
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
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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
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
Subjects affected by abdominal aortic aneurysms undergoing aortic surgical procedures
Description
Inclusion Criteria:
- Eligible subjects undergoing aortic surgical procedures
- Ejection fraction (FE) > 30%
- Acceptance and signature of the informed consent
Exclusion Criteria:
- Acute myocardial infarction in the last 6 months
- Chronic and acute Inflammatory diseases
- Immunological and rheumatic diseases
- Pre-existing or ongoing neoplasms
- infectious diseases
- 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
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison between the levels of Hippo signaling and autophagy markers observed in aortic aneurysms and the levels assessed in the adjacent non-aneurysmatic aortic portions.
Time Frame: 1 month
|
Quantification by immunoblot of markers of Hippo signaling (MST1, YAP) and autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1.
Adjacent aortic fragments without aneurysm belonging to the same patient will be used as control.
|
1 month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Impact of cardiovascular risk factors on the autophagy levels in aortic samples of patients undergoing surgical procedure of aortic aneurysm removal.
Time Frame: 1 month
|
Quantification by immunoblot of markers of autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1) and its statistical correlation with cardiovascular risk factors, such as age, diabetes, obesity, hypercholesterolemia, metabolic syndrome
|
1 month
|
Correlation between levels of autophagy and apoptosis in aneurysmal samples
Time Frame: 1 month
|
Quantification by immunoblot of markers of autophagy and apoptosis
|
1 month
|
Correlation between levels of autophagy and endothelial function in patients undergoing surgical procedure of aortic aneurysm removal
Time Frame: 1 month
|
flow- mediated dilatation (FMD) in subject underwent surgical procedure of aortic substitution/dissection
|
1 month
|
Correlation between levels of autophagy and the size of aortic aneurysms
Time Frame: 1 month
|
Aneurysmal dimension will be evaluated by CT angiography
|
1 month
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation between autophagy, oxidative stress and inflammation
Time Frame: 1 month
|
western blot for markers of autophagy, ELISA and High Performance Liquid Chromatography (HPLC) analyses for markers of oxidative stress
|
1 month
|
Correlation between levels of autophagy and the Hippo pathway
Time Frame: 1 month
|
western blot for marker of autophagy and the Hippo pathway
|
1 month
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Giacomo Frati, MD, IRCCS Neuromed
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)
June 1, 2017
Primary Completion (ACTUAL)
October 31, 2017
Study Completion (ACTUAL)
November 1, 2017
Study Registration Dates
First Submitted
July 5, 2017
First Submitted That Met QC Criteria
July 5, 2017
First Posted (ACTUAL)
July 7, 2017
Study Record Updates
Last Update Posted (ACTUAL)
April 11, 2022
Last Update Submitted That Met QC Criteria
April 8, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 6-2017
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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