Ulcer VenousSER-VES-HEALNCT04652531
Autologous Serum-derived EV for Venous Trophic Lesions Not Responsive to Conventional Treatments
A study testing Autologous extracellular vesicles from serum in people with Ulcer Venous, run by University of Turin, Italy at 1 site in Italy.
Trial summary
Venous ulcers are defined by the presence of open lesions which represent the final stage of chronic venous disease or post-thrombotic syndrome. The risk factors for the development of venous ulcers include age, obesity, female sex, trauma, immobility, factor V mutation, thrombosis, venous agenesis. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ulcer Venous
- What is being tested?
- Autologous extracellular vesicles from serum
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 18 Sep 2020to 31 Dec 2024
- Phase
- Interventional
- 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
Who may be able to join
- -
Who cannot join
- :> 85 years, diabetics, autoimmune diseases, neoplastic, arterial disease of the lower limbs.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
AOU San Giovanni Battista
Turin, 10126
Maria Felice Brizzi, MD, +390116706653, mariafelice.brizzi@unito.it
Giovanni Camussi, MD, +390116709588, giovanni.camussi@unito.it
About this study
Official title: Autologous Serum-derived Extracellular Vesicles to Treat Venous Trophic Lesions Not Responsive to Conventional Treatments
Venous ulcers are defined by the presence of open lesions which represent the final stage of chronic venous disease or post-thrombotic syndrome. The risk factors for the development of venous ulcers include age, obesity, female sex, trauma, immobility, factor V mutation, thrombosis, venous agenesis.
Recommendation by the current guidelines includes compression and advanced dressing. However, in several cases, they fail to change patients' outcome. The aim of this study is to identify an alternative therapy to treat venous trophic lesions not responding to traditional therapeutic approaches using extracellular vesicles obtained from autologous serum.
Read the detailed description
In recent years, several in vitro and in vivo studies have provided been the beneficial effects of stem cells for tissue regeneration. Moreover, several randomized trials are ongoing and the interim results seem to give promising results and indicate their safety. Alternative approaches have recently been proposed, such as the injection of platelet preparation or the use of acellular amniotic membranes or extracellular vesicles (EV). EV act as cell-to-cell paracrine or endocrine-like communication mechanisms. The therapeutic potential of EV depends on the transfer of their cargo(proteins, RNAs, DNA, lipids, etc) to target cells (1). In the last decades, several pre-clinical studies have demonstrated safety. A pilot study was recently published on the use of EV as an effective treatment for retinal damage. At the University of Turin using a mouse model of ischemia/ reperfusion of the lower limb it was demonstrated that the intramuscular administration of EV obtained from the serum of healthy donors was associated with a higher density of local capillaries and an increase in laser Doppler signal compared to controls (2). A simple in vitro functional potency assay was developed, which allowed predicting EV therapeutic efficacy in vivo. The best response was obtained by intravenous administration immediately after surgical ligation and intramuscular in the next two days (T1 and T2). Through the Laser Doppler study, distal perfusion was evaluated after 7 days, which showed a clear improvement and protection of muscle damage. A more recent study has shown that even subjects with high cardiovascular risk (diabetic, obese, diabetic/obese and with arterial disease of the lower limbs) can benefit from the use of autologous EV (3).
The pilot study will involve the enrollment of 10 patients with bilateral venous ulcer refractory to conventional treatment for more than 6 months, recruited at the Vascular Ulcer Clinic of University Vascular Surgery. At the time of recruitment, venous Eco Doppler will be performed to evaluate the superficial and deep venous and arterial system to exclude possible "mixed" etiologies. A blood sample will then recovered for EV isolation in collaboration with the Blood Bank of the City of Health and Science of Turin. The characteristics of the ulcer will be entered in the database: dimensions (photo), margins, bottom and a swab for microbiology will be performed. Patients whose swab will be positive will be excluded.
EV will be analysed for their biological activity using the potency assay and will be used only if found to be effective (potency test). Subsequently, peri-wound injection of EV will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied. As an internal control, the contralateral ulcer will be treated with a standard dressing and an elastic compression bandage. The patients will be evaluated on an outpatient basis on day 3 and then weekly. The results of treated patients will be collected in a dedicated database.
- Conditions
- Ulcer Venous
- Being tested
- Autologous extracellular vesicles from serum
- Keywords
- Autologous EV, serum, ulcers, vascular disease
- Medical subject headings
- Varicose Ulcer, Ulcer, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous extracellular vesicles from serumOther
Peri-wound injection of the vesicles will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | In the treatment arm, the lesion will be treated with EV for 3 weeks once a week Receives: Other: Autologous extracellular vesicles from serum |
| Internal control | Sham comparator | The contralateral ulcer will be treated with a standard dressing and an elastic-compression bandage for 3 weeks. Receives: Other: Autologous extracellular vesicles from serum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the ulcer area from baseline to eight weeks
Ulcer areas will be recorded at baseline and weekly using digital camera. A standard rule was positioned on the surface of the skin around the ulcers to standardize the images and to allow data analysis. The ImageJ analysis program will be used to calculate the ulcer area. A blinded investigator manually delimitated the ulcer area to calculate the area. The total area will be expressed in square centimeters.
Measured: 8 weeks
Secondary outcomes (1)
Pain change
All patients should record their subjective feelings, including pain, burning and secretions. The level of pain will be monitored during the treatment as patient's experienced pain (decrease, unchange and/or increase). The amount of secretion will be classified as follow: absent, small, moderate, or abundant.
Measured: 8 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2020
- Study start18 Sep 2020
- Primary completion30 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ulcer VenousStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Peri-wound injection of the vesicles will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied. The contralateral ulcer will be treated with a standard dressing and an elastic compression bandage. The patients will be evaluated on an outpatient basis on day 3 and then weekly.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Felice Brizzi, University of Turin, Italy
- Investigators
- Maria Felice Brizzi, MD, Principal investigator, University of Turin, ItalyGiovanni Camussi, MD, Study chair, University of Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04652531
- Sponsor's protocol ID
- CS2/1095/0090491
- Acronym
- SER-VES-HEAL
- Status last verified
- May 2023
- First submitted
- 23 Nov 2020
- Last updated
- 12 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kholia S, Ranghino A, Garnieri P, Lopatina T, Deregibus MC, Rispoli P, Brizzi MF, Camussi G. Extracellular vesicles as new players in angiogenesis. Vascul Pharmacol. 2016 Nov;86:64-70. doi: 10.1016/j.vph.2016.03.005. Epub 2016 Mar 22.
PubMed 27013016Cavallari C, Ranghino A, Tapparo M, Cedrino M, Figliolini F, Grange C, Giannachi V, Garneri P, Deregibus MC, Collino F, Rispoli P, Camussi G, Brizzi MF. Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia. Sci Rep. 2017 Aug 15;7(1):8180. doi: 10.1038/s41598-017-08250-0.
PubMed 28811546Cavallari C, Figliolini F, Tapparo M, Cedrino M, Trevisan A, Positello L, Rispoli P, Solini A, Migliaretti G, Camussi G, Brizzi MF. miR-130a and Tgfbeta Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential. Sci Rep. 2020 Jan 20;10(1):706. doi: 10.1038/s41598-019-55783-7.
PubMed 31959759
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Serum-derived Extracellular Vesicles to Treat Venous Trophic Lesions Not Responsive to Conventional Treatments
- ClinicalTrials.gov ID
- NCT04652531
- Acronym / sponsor ID
- SER-VES-HEAL / CS2/1095/0090491
- Conditions
- Ulcer Venous
- Keywords
- Autologous EV, serum, ulcers, vascular disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- 18 Sep 2020 (actual)
- Primary completion
- 30 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 3 Dec 2020 (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.
Venous ulcers are defined by the presence of open lesions which represent the final stage of chronic venous disease or post-thrombotic syndrome. The risk factors for the development of venous ulcers include age, obesity, female sex, trauma, immobility, factor V mutation, thrombosis, venous agenesis.
Recommendation by the current guidelines includes compression and advanced dressing. However, in several cases, they fail to change patients' outcome. The aim of this study is to identify an alternative therapy to treat venous trophic lesions not responding to traditional therapeutic approaches using extracellular vesicles obtained from autologous serum.
Detailed description
In recent years, several in vitro and in vivo studies have provided been the beneficial effects of stem cells for tissue regeneration. Moreover, several randomized trials are ongoing and the interim results seem to give promising results and indicate their safety. Alternative approaches have recently been proposed, such as the injection of platelet preparation or the use of acellular amniotic membranes or extracellular vesicles (EV). EV act as cell-to-cell paracrine or endocrine-like communication mechanisms. The therapeutic potential of EV depends on the transfer of their cargo(proteins, RNAs, DNA, lipids, etc) to target cells (1). In the last decades, several pre-clinical studies have demonstrated safety. A pilot study was recently published on the use of EV as an effective treatment for retinal damage. At the University of Turin using a mouse model of ischemia/ reperfusion of the lower limb it was demonstrated that the intramuscular administration of EV obtained from the serum of healthy donors was associated with a higher density of local capillaries and an increase in laser Doppler signal compared to controls (2). A simple in vitro functional potency assay was developed, which allowed predicting EV therapeutic efficacy in vivo. The best response was obtained by intravenous administration immediately after surgical ligation and intramuscular in the next two days (T1 and T2). Through the Laser Doppler study, distal perfusion was evaluated after 7 days, which showed a clear improvement and protection of muscle damage. A more recent study has shown that even subjects with high cardiovascular risk (diabetic, obese, diabetic/obese and with arterial disease of the lower limbs) can benefit from the use of autologous EV (3).
The pilot study will involve the enrollment of 10 patients with bilateral venous ulcer refractory to conventional treatment for more than 6 months, recruited at the Vascular Ulcer Clinic of University Vascular Surgery. At the time of recruitment, venous Eco Doppler will be performed to evaluate the superficial and deep venous and arterial system to exclude possible "mixed" etiologies. A blood sample will then recovered for EV isolation in collaboration with the Blood Bank of the City of Health and Science of Turin. The characteristics of the ulcer will be entered in the database: dimensions (photo), margins, bottom and a swab for microbiology will be performed. Patients whose swab will be positive will be excluded.
EV will be analysed for their biological activity using the potency assay and will be used only if found to be effective (potency test). Subsequently, peri-wound injection of EV will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied. As an internal control, the contralateral ulcer will be treated with a standard dressing and an elastic compression bandage. The patients will be evaluated on an outpatient basis on day 3 and then weekly. The results of treated patients will be collected in a dedicated database.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Peri-wound injection of the vesicles will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied. The contralateral ulcer will be treated with a standard dressing and an elastic compression bandage. The patients will be evaluated on an outpatient basis on day 3 and then weekly.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Other: Autologous extracellular vesicles from serumIn the treatment arm, the lesion will be treated with EV for 3 weeks once a week |
| Internal control | Sham comparator | Other: Autologous extracellular vesicles from serumThe contralateral ulcer will be treated with a standard dressing and an elastic-compression bandage for 3 weeks. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- -
Key exclusion criteria (1 listed)
- :> 85 years, diabetics, autoimmune diseases, neoplastic, arterial disease of the lower limbs.
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 |
|---|---|---|
| Autologous extracellular vesicles from serumPeri-wound injection of the vesicles will be performed in a sterile environment. Sterile gauze and an elastic-compression bandage will be applied. | Other | Internal control, Treatment |
Primary outcome
Changes in the ulcer area from baseline to eight weeks
Time frame: 8 weeks
Ulcer areas will be recorded at baseline and weekly using digital camera. A standard rule was positioned on the surface of the skin around the ulcers to standardize the images and to allow data analysis. The ImageJ analysis program will be used to calculate the ulcer area. A blinded investigator manually delimitated the ulcer area to calculate the area. The total area will be expressed in square centimeters.
1 secondary outcome
Pain change
Time frame: 8 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2023.
- Results publication: PubMed 27013016Kholia S, Ranghino A, Garnieri P, Lopatina T, Deregibus MC, Rispoli P, Brizzi MF, Camussi G. Extracellular vesicles as new players in angiogenesis. Vascul Pharmacol. 2016 Nov;86:64-70. doi: 10.1016/j.vph.2016.03.005. Epub 2016 Mar 22.
- Results publication: PubMed 28811546Cavallari C, Ranghino A, Tapparo M, Cedrino M, Figliolini F, Grange C, Giannachi V, Garneri P, Deregibus MC, Collino F, Rispoli P, Camussi G, Brizzi MF. Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia. Sci Rep. 2017 Aug 15;7(1):8180. doi: 10.1038/s41598-017-08250-0.
- Results publication: PubMed 31959759Cavallari C, Figliolini F, Tapparo M, Cedrino M, Trevisan A, Positello L, Rispoli P, Solini A, Migliaretti G, Camussi G, Brizzi MF. miR-130a and Tgfbeta Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential. Sci Rep. 2020 Jan 20;10(1):706. doi: 10.1038/s41598-019-55783-7.
- 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.
Maria Felice Brizzi, MD principal investigator
University of Turin, Italy
Giovanni Camussi, MD study chair
University of Turin, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Autologous extracellular vesicles from serum in people with Ulcer Venous, run by University of Turin, Italy 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 1 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 12 May 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. Some participants in this study may receive a placebo. 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 Maria Felice Brizzi, MD (+390116706653, mariafelice.brizzi@unito.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the ulcer area from baseline to eight weeks (time frame: 8 weeks). 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 NCT04652531, which also lists 3 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 12 May 2023.