Acute Lung Injury (ALI)NCT04546919
Effect of R-spondin3 on Sepsis Induced Endothelial Dysfunction
An observational study of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS), run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS)
- What is being tested?
- sepsis
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 8 Jul 2020to 12 Dec 2021
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: septic patients
Who may be able to join
- patients with sepsis defined as SIRS combined with an infectious episode and dysfunction of one or more organ
- age older than 18 years
- SIRS is considered to be present when patients have more than one of the following clinical findings:
- Body temperature higher than 38°C or lower than 36°C;
- Heart rate higher than 90/min
- Hyperventilation evidenced by respiratory rate higher than 20/min or PaCO2 lower than 32 mmHg;
- White blood cell count higher than 12,000 cells/ µl or lower than 4,000/ µl.
Who cannot join
- patients younger than 18
- women during pregnancy or lactation; being involved in other clinical subjects.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Anesthesia, Shanghai Xinhua hospital
Shanghai, Shanghai Municipality, 200082
Lai Jiang, chief doctor, +86-2125077821, jianglai@xinhuamed.com.cn
About this study
Official title: the Mechanism of the Downregulation of R-spondin3 in Sepsis Induced Lung Injury
Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
The human and mouse R-spondins encode a family of proteins that includes four paralogs (R-spo1-4). R-spondins are secreted proteins found primarily in the extracellular region and are known to promote β-catenin signaling. Among them, the embryonic lethal vascular remodeling phenotype of R-spondin3 (Rspo3) mutant mice suggests a role of EC derived Rspo3 in angiogenesis. Rspo3 protects tissues against mesenteric I/R by tightening endothelial cell junction and improving vascular intergrity. However, the role of Rspo3 in sepsis-induced pulmonary endothelial dysfunction remains unclear. Thus, it is worthwhile to explore the relationship between Rspo3 and sepsis-induced lung injury, which will be helpful for prevention and treatment of sepsis-induced lung injury and endothelial dysfunction.
Read the detailed description
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), is a clinical problem induced by acute and excessive pulmonary inflammation. Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, and a major cause of death for sepsis patients is respiratory failure. Despite modern clinical practices in critical care medicine, there still remains a mortality rate as high as 45%. In addition, Vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. Endothelial cell activation is associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
The human and mouse R-spondins encode a family of proteins that includes four paralogs (R-spo1-4). R-spondins are secreted proteins found primarily in the extracellular region and are known to promote β-catenin signaling. Among them, the embryonic lethal vascular remodeling phenotype of R-spondin3 (Rspo3) mutant mice suggests a role of EC derived Rspo3 in angiogenesis. Former studies demonstrated that endothelial Rspo3 enhances cell autonomous non-canonical Wnt signaling, thereby preventing retinal and tumor blood vessel regression and EC apoptosis. The mid-gestational lethality of Rspo3-ECKO mice indicated a role of EC-derived RSPO3 in controlling blood vessel remodeling. Furthermore, Rspo3 protects tissues against mesenteric I/R by tightening endothelial cell junction and improving vascular intergrity. However, the role of Rspo3 in sepsis-induced pulmonary endothelial dysfunction remains unclear. Thus, it is worthwhile to explore the relationship between Rspo3 and sepsis-induced lung injury.
In the present study, the investigators will analyze the expression of Rspo3 in septic patients and sepsis-induced lung injury models and explore whether Rspo3 could protect sepsis-associated lung injury, which will be helpful for prevention and treatment of sepsis-induced lung injury and endothelial dysfunction.
- Being tested
- sepsis
- Keywords
- sepsis, Rspondin3, ALI
- Medical subject headings
- Acute Lung Injury, Respiratory Distress Syndrome, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sepsisOther
Body temperature higher than 38°C or lower than 36°C; Heart rate higher than 90/min; Hyperventilation evidenced by respiratory rate higher than 20/min or PaCO2 lower than 32 mmHg; White blood cell count higher than 12,000 cells/ µl or lower than 4,000/ µl.
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Concentration of R-spondin 3
The venous blood samples were collected from septic patients after the onset of the sepsis, plasma were separated by centrifugation and detected for R-spondin3 concentration.
Measured: after initiation of sepsis within 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study start8 Jul 2020
- Primary completion8 Aug 2021 (estimated)
- Study completion12 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lung Injury (ALI)Studies of the same condition, open and under way.
- More trials run by Xinhua Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lai Jiang, chief doctor, Study chair, Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04546919
- Sponsor's protocol ID
- XHEC-C-2020-084
- Status last verified
- Jul 2020
- First submitted
- 19 Aug 2020
- Last updated
- 14 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- the Mechanism of the Downregulation of R-spondin3 in Sepsis Induced Lung Injury
- ClinicalTrials.gov ID
- NCT04546919
- Acronym / sponsor ID
- XHEC-C-2020-084
- Keywords
- sepsis, Rspondin3, ALI
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 8 Jul 2020 (actual)
- Primary completion
- 8 Aug 2021 (estimated)
- Study completion
- 12 Dec 2021 (estimated)
- First posted
- 14 Sep 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.
Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
The human and mouse R-spondins encode a family of proteins that includes four paralogs (R-spo1-4). R-spondins are secreted proteins found primarily in the extracellular region and are known to promote β-catenin signaling. Among them, the embryonic lethal vascular remodeling phenotype of R-spondin3 (Rspo3) mutant mice suggests a role of EC derived Rspo3 in angiogenesis. Rspo3 protects tissues against mesenteric I/R by tightening endothelial cell junction and improving vascular intergrity. However, the role of Rspo3 in sepsis-induced pulmonary endothelial dysfunction remains unclear. Thus, it is worthwhile to explore the relationship between Rspo3 and sepsis-induced lung injury, which will be helpful for prevention and treatment of sepsis-induced lung injury and endothelial dysfunction.
Detailed description
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), is a clinical problem induced by acute and excessive pulmonary inflammation. Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, and a major cause of death for sepsis patients is respiratory failure. Despite modern clinical practices in critical care medicine, there still remains a mortality rate as high as 45%. In addition, Vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. Endothelial cell activation is associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
The human and mouse R-spondins encode a family of proteins that includes four paralogs (R-spo1-4). R-spondins are secreted proteins found primarily in the extracellular region and are known to promote β-catenin signaling. Among them, the embryonic lethal vascular remodeling phenotype of R-spondin3 (Rspo3) mutant mice suggests a role of EC derived Rspo3 in angiogenesis. Former studies demonstrated that endothelial Rspo3 enhances cell autonomous non-canonical Wnt signaling, thereby preventing retinal and tumor blood vessel regression and EC apoptosis. The mid-gestational lethality of Rspo3-ECKO mice indicated a role of EC-derived RSPO3 in controlling blood vessel remodeling. Furthermore, Rspo3 protects tissues against mesenteric I/R by tightening endothelial cell junction and improving vascular intergrity. However, the role of Rspo3 in sepsis-induced pulmonary endothelial dysfunction remains unclear. Thus, it is worthwhile to explore the relationship between Rspo3 and sepsis-induced lung injury.
In the present study, the investigators will analyze the expression of Rspo3 in septic patients and sepsis-induced lung injury models and explore whether Rspo3 could protect sepsis-associated lung injury, which will be helpful for prevention and treatment of sepsis-induced lung injury and endothelial dysfunction.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- septic patients
Key inclusion criteria (7 listed)
- patients with sepsis defined as SIRS combined with an infectious episode and dysfunction of one or more organ
- age older than 18 years
- SIRS is considered to be present when patients have more than one of the following clinical findings:
- Body temperature higher than 38°C or lower than 36°C;
- Heart rate higher than 90/min
Key exclusion criteria (2 listed)
- patients younger than 18
- women during pregnancy or lactation; being involved in other clinical subjects.
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 |
|---|---|---|
| sepsisBody temperature higher than 38°C or lower than 36°C; Heart rate higher than 90/min; Hyperventilation evidenced by respiratory rate higher than 20/min or PaCO2 lower than 32 mmHg; White blood cell count higher than 12,000 cells/ µl or lower than 4,000/ µl. | Other | – |
Primary outcome
Change in Plasma Concentration of R-spondin 3
Time frame: after initiation of sepsis within 24 hours
The venous blood samples were collected from septic patients after the onset of the sepsis, plasma were separated by centrifugation and detected for R-spondin3 concentration.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
- Individual participant dataSharing planned: Undecided
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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.
Lai Jiang, chief doctor study chair
Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
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 Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS), run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
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 7 inclusion and 2 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 14 Sep 2020. 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 China. 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?
Contact Lai Jiang, chief doctor (+86-2125077821, jianglai@xinhuamed.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Plasma Concentration of R-spondin 3 (time frame: after initiation of sepsis within 24 hours). 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 14 Sep 2020.