Aortic AneurysmNCT03211000
Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm
An observational study of Aortic Aneurysm, run by Neuromed IRCCS at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Aortic Aneurysm
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2017to 1 Nov 2017
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Subjects affected by abdominal aortic aneurysms undergoing aortic surgical procedures
Who may be able to join
- Eligible subjects undergoing aortic surgical procedures
- Ejection fraction (FE) > 30%
- Acceptance and signature of the informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Aortic Aneurysm
- Keywords
- aortic aneurysm, autophagy, oxidative stress, Hippo pathway
- Medical subject headings
- Aortic Aneurysm
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: 1 month
Secondary outcomes (4)
Impact of cardiovascular risk factors on the autophagy levels in aortic samples of patients undergoing surgical procedure of aortic aneurysm removal.
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
Measured: 1 month
Correlation between levels of autophagy and apoptosis in aneurysmal samples
Quantification by immunoblot of markers of autophagy and apoptosis
Measured: 1 month
Correlation between levels of autophagy and endothelial function in patients undergoing surgical procedure of aortic aneurysm removal
flow- mediated dilatation (FMD) in subject underwent surgical procedure of aortic substitution/dissection
Measured: 1 month
Correlation between levels of autophagy and the size of aortic aneurysms
Aneurysmal dimension will be evaluated by CT angiography
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start1 Jun 2017
- Primary completion31 Oct 2017
- Study completion1 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic AneurysmStudies 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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuromed IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maurizio Forte, Neuromed IRCCS
- Investigators
- Giacomo Frati, MD, Principal investigator, IRCCS Neuromed
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211000
- Sponsor's protocol ID
- 6-2017
- Status last verified
- Apr 2022
- First submitted
- 5 Jul 2017
- Last updated
- 11 Apr 2022
- 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 11 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Molecular Mechanisms Associated With the Formation of Human Aortic Aneurysm: a Focus on Autophagy, Oxidative Stress and Hippo Signaling
- ClinicalTrials.gov ID
- NCT03211000
- Acronym / sponsor ID
- 6-2017
- Conditions
- Aortic Aneurysm
- Keywords
- aortic aneurysm, autophagy, oxidative stress, Hippo pathway
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Neuromed IRCCSUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 1 Nov 2017 (actual)
- First posted
- 7 Jul 2017 (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 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.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects affected by abdominal aortic aneurysms undergoing aortic surgical procedures
Key inclusion criteria (3 listed)
- Eligible subjects undergoing aortic surgical procedures
- Ejection fraction (FE) > 30%
- Acceptance and signature of the informed consent
Key exclusion criteria (8 listed)
- Acute myocardial infarction in the last 6 months
- Chronic and acute Inflammatory diseases
- Immunological and rheumatic diseases
- Pre-existing or ongoing neoplasms
- infectious diseases
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
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.
4 secondary outcomes
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
Correlation between levels of autophagy and apoptosis in aneurysmal samples
Time frame: 1 month
Correlation between levels of autophagy and endothelial function in patients undergoing surgical procedure of aortic aneurysm removal
Time frame: 1 month
Correlation between levels of autophagy and the size of aortic aneurysms
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2022.
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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.
Giacomo Frati, MD principal investigator
IRCCS Neuromed
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 Aortic Aneurysm, 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 3 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: finished, as of the sponsor's last update on 11 Apr 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). 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 11 Apr 2022.