Diabetes MellitusNETsNCT06821919
Impact of Antiglycemic & Immunosuppressive Therapies on NETosis in Diabetes & Kidney Disease (NETs - Neutrophil Traps)
An observational study of Diabetes Mellitus and Kidney Disease, run by Western Galilee Hospital-Nahariya at 1 site in Israel.
Trial summary
This study aims to investigate whether new glucose-lowering medications, such as SGLT2 inhibitors (e.g., Forxiga/Jardiance) and GLP-1 receptor agonists (e.g., Ozempic), can reduce NETosis in diabetic patients, thereby mitigating secondary complications such as cardiovascular disease and kidney damage. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Kidney Disease
- How many people
- 70 participants
- Where
- 1 siteIsrael
- Study dates
- 13 May 2024to 30 Dec 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: DM therapy study: - Diabetic patients aged 18 years or older (men and women). * Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. • Exclusion Criteria: * Patients with conditions affecting NETosis, including autoimmunity, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. Chronic kidney disease (CKD) patients :This study will include 50 CKD patients with various etiologies, with a focus on those with immune-mediated kidney diseases, such as ANCA-associated vasculitis. The primary aim is to evaluate the effects of immunosuppressive therapy on NETosis. All patients will be naïve to prior immunosuppressive therapy to ensure the observed effects are directly attributable to the initiation of treatment. • Exclusion Criteria: o Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
Who may be able to join
- DM therapy study: - Diabetic patients aged 18 years or older (men and women).
- Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists.
- -Chronic kidney disease (CKD) patients :50 CKD patients with various etiologies.
- Focus:
- This part of the study will specifically evaluate immune-mediated kidney disease, such as ANCA-associated vasculitis, and the effects of immunosuppressive therapy on NETosis.
- Exclusion Criteria:
- Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Olga Vdovich, MD contact
Israel1 site, 1 recruiting
- Recruiting
Galilee Medical Center
Nahariya, 2210001
Etty Kruzel-Davila, MD, 972-4-9107619, ETTYK@gmc.gov.il
About this study
Official title: Evaluating the Effect of Hemodialysis Modality and New Anti-glycemic Drugs on NETosis on in Hemodialysis and Diabetic Patient, and Assessment of NETosis in Various Kidney Diseases
This study aims to investigate whether new glucose-lowering medications, such as SGLT2 inhibitors (e.g., Forxiga/Jardiance) and GLP-1 receptor agonists (e.g., Ozempic), can reduce NETosis in diabetic patients, thereby mitigating secondary complications such as cardiovascular disease and kidney damage. By targeting dysregulated NET formation, the study seeks to establish a link between reduced NETosis and improved clinical outcomes in diabetes.
Additionally, the study will evaluate the effects of immunosuppressive therapies on NETosis in patients with immune-mediated kidney diseases, such as ANCA-associated vasculitis. By correlating NETosis activity with disease progression and treatment response, this research will assess whether reducing NETosis contributes to better management of inflammation and secondary morbidity in these conditions.
Through these evaluations, the study aims to identify potential therapeutic strategies to improve outcomes in both diabetic and chronic kidney disease populations.
Read the detailed description
Neutrophil extracellular traps (NETs) are an essential component of the innate immune system, designed to trap and neutralize invading pathogens. NETosis, the process by which neutrophils release decondensed chromatin (DNA and histones) decorated with antimicrobial proteins such as myeloperoxidase (MPO) and neutrophil elastase (NE), is a critical mechanism in host defense. This process is induced by stimuli such as PMA, antibodies, cytokines, chemokines, and sterile triggers, including high glucose, cholesterol, and hypoxia. This stimulation activates the Raf-MEK-ERK pathway and NADPH oxidase-dependent production of reactive oxygen species.1,2 An increase in cytosolic calcium cations activates NADPH oxidases and acts as a cofactor for peptidylarginine deiminase 4 (PAD4). PAD4 catalyzes citrullinated histone H3 (Cit-H3) inducing chromatin decondensation, resulting in a cell extrusion of mixture of DNA and bactericidal proteins, including MPO and NE, which all serves as a specific markers of NETosis.1,2 While beneficial in infection settings, excessive or dysregulated NET formation can cause significant tissue damage and organ dysfunction. NETs have been implicated in the pathogenesis of various acute and chronic inflammatory diseases, including myocardial infarction, atherosclerosis, autoimmune diseases, diabetes, and chronic kidney disease (CKD). Elevated NETosis markers, including cell-free DNA (cfDNA) and Cit-H3, are commonly observed in these conditions, underscoring their role in disease progression.3 Given the dual nature of NETosis, understanding how different factors influence this process is critical for developing targeted therapies. This study focuses on two key aspects: evaluating the effects of antiglycemic medications on NETosis and investigating NETosis across different stages of immune-mediated kidney disease before and after immunosuppressive therapy.
(The hemodialysis part of this trial is not included in the current protocol)
Part 1: Evaluating the Effects of Antiglycemic Medications on NETosis Dysregulated NETosis in diabetic and CKD patients contributes to systemic inflammation and organ damage. Studies have shown elevated levels of NETosis markers, such as cfDNA and Cit-H3, in these populations. While metformin has demonstrated the ability to reduce NET formation in diabetic patients, the effects of newer glucose-lowering agents, including SGLT2 inhibitors and GLP-1 receptor agonists, remain unexplored.4 Both SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated robust cardiovascular and renal protective effects.5 This study aims to evaluate their impact on basal and stimulated NETosis in diabetic and CKD patients with various etiologies. By analyzing NETosis markers before and after treatment, this research will provide insights into whether these agents can modulate NETosis, thereby offering additional anti-inflammatory benefits and reducing disease-associated complications.
Part 2: Evaluating NETosis at Different Stages of Immune-Mediated Kidney Disease and After Immunosuppressive Therapy Immune-mediated kidney diseases, such as ANCA-associated vasculitis, involve heightened NETosis that contributes to kidney injury and systemic inflammation.2 Chronic kidney disease resulting from these conditions often exhibits elevated NET formation, exacerbating disease progression. This study seeks to investigate the dynamics of NETosis at various stages of CKD caused by immune-mediated diseases.
In addition, the effects of immunosuppressive therapy on NETosis will be assessed. Immunosuppressive medications, a cornerstone in the treatment of diseases like ANCA-associated vasculitis, can influence neutrophil activity. By monitoring NETosis markers, including cfDNA, Cit-H3, MPO, and NE, before and after initiating immunosuppressive therapy, the study aims to identify patterns of response and the potential therapeutic modulation of NETosis.
Conclusion This comprehensive investigation into the effects of antiglycemic medications and immunosuppressive therapy on NETosis will provide critical insights into the interplay between treatment, inflammation, and disease progression in diabetic and CKD patients. These findings may help pave the way for targeted interventions aimed at modulating NETosis and improving outcomes in high-risk populations.
- Conditions
- Diabetes Mellitus, Kidney Disease
- Keywords
- NETosis, Diabetes mellitus, kidney disease, glomerulonephritis
- Medical subject headings
- Diabetes Mellitus, Kidney Diseases, Glomerulonephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Diabetes mellitus patients | 2. Diabetic Patients (DM Therapy Study) * Sample Size: 20 diabetic patients. * Group 1: 10 patients treated with Forxiga/Jardiance (SGLT2 inhibitors). * Group 2: 10 patients treated with Ozempic (GLP-1 agonist). * Patient Criteria: o Patients naïve to SGLT2 inhibitors and GLP-1 receptor agonists to ensure the observed effects are attributable to the initiation of these therapies. * Sample Collection: * Serum samples (6 ml in serum separator tubes). * Two tubes (12 ml total) will be collected per participant at each time point: Before starting treatment and at 1, 2, 3, 6, and 12 months after initiating medication. * Inclusion Criteria: * Diabetic patients aged 18 years or older (men and women). * Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. * Exclusion Criteria: * Patients with conditions affecting NETosis, including autoimmunity, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. | |
| Chronic kidney disease (CKD) patients | Chronic Kidney Disease (CKD) Patients (Evaluation of Immunosuppressive Therapy) * Sample Size: 50 CKD patients with various etiologies. * Focus: o This part of the study will specifically evaluate immune-mediated kidney disease, such as ANCA-associated vasculitis, and the effects of immunosuppressive therapy on NETosis. * Objective: * Assess NETosis markers (e.g., cfDNA, Cit-H3, MPO, NE) before initiating immunosuppressive treatment and at 1, 2, 3, 6, and 12 months of therapy. * Correlate NETosis dynamics with clinical variables, including disease activity, renal function, and inflammatory markers. * Sample Collection: o Serum samples (6 ml in serum separator tubes). o Two tubes (12 ml total) will be collected per participant at each time point: Before starting treatment and at 1, 2, 3, 6, and 12 months after initiating medication. * Exclusion Criteria: * Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. | |
| 10 healthy participants will be recruited to the control group (for both studies). | Control Group * Sample Size: 10 healthy participants. * Objective: o Serve as controls for both the diabetic and CKD studies. * Sample Collection: * Two tubes (12 ml total) will be collected per participant * Eligibility: * Healthy individuals without underlying medical conditions. |
What is being measured
The primary outcome is the main question the study is designed to answer.
NETosis marker- citrullinated histone H3 (citH3)
- NETosis markers: NET formation will be assessed in sera blood samples across all groups.
- Focus on Naïve Patients: Emphasis will be placed on evaluating the initial effects of antiglycemic medications in diabetic patients and the impact of immunosuppressive therapy in CKD patients with immune-mediated diseases.
- Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment.
All serum samples will be diluted 1:2 and citrullinated histone H3 (citH3) will be quantified using the Citrullinated Histone H3 ELISA Kit: O.D. (501620; Cayman Chemical, Ann Arbor, USA).
Measured: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
NETosis marker- Myeloperoxidase
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment.
All serum samples will be diluted 1:2 . MPO measurement will be conducted using Myeloperoxidase ELISA Kit , ng/ml (501410; Cayman Chemical).
Measured: Before treatment, 1,2,3,6 and12 moths after treatment.
NETosis marker- Neutrophil elastase (NE)
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment.
All serum samples will be diluted 1:2 , and NE measurement will be conducted using Human Neutrophil Elastase ELISA Kit, ng/ml (ab204730; Abcam
Measured: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
NETosis marker: Peptidylarginine deiminase 4-PAD4
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment.
All serum samples will be diluted 1:2 and PAD4 measurement will be conducted using (PADI4 ELISA Kit, ng/ml (ELH-PADI4, RayBiotech) according to the manufacturer's instructions
Measured: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
Secondary outcomes (4)
Kidney function
- Kidney Function
- Estimated glomerular filtration rate (eGFR, ml/min) will be measured using CKD-EPI creatinine) equation.
- These measures will monitor changes in kidney function over time and will be correlated with NETosis markers assessed prior to and during treatment.
Measured: Before treatment, 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy.
Urine protein/ creatinine ratio
Urine protein/ creatinine ratio w (mg/gr) will be measured.
- These measures will monitor changes in kidney function over time and will be correlated with NETosis markers assessed prior to and during treatment
Measured: Before treatment, 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
Major adverse cardiovascular events (MACE)
Major adverse cardiovascular events (MACE): Including myocardial infarction, stroke, heart failure and cardiovascular death (present/absent).
- Yearly analyses will evaluate the occurrence of these events in relation to NETosis markers
Measured: 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
All cause mortality
All-cause mortality: Survival outcomes will be tracked through yearly analyses.
- Correlations will be drawn between NETosis markers and mortality rates to understand their predictive value and treatment effects. These secondary outcomes will highlight the association between NETosis and long-term renal and cardiovascular outcomes
Measured: 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2025
- Study start13 May 2024
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Galilee Hospital-Nahariya
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Etty Kruzel-Davila, Western Galilee Hospital-Nahariya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06821919
- Sponsor's protocol ID
- 0108-22-NHR
- Acronym
- NETs
- Status last verified
- Feb 2025
- First submitted
- 26 Jan 2025
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All anonymized data collected during the study will be made available upon reasonable request. This ensures transparency and allows for independent validation of the findings while protecting participant privacy. Identifiable information will be removed, and data will only be shared in a de-identified format, ensuring that participants cannot be traced back based on the shared data. Access to the anonymized dataset will require approval from the principal investigator to ensure appropriate use and adherence to ethical standards.
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effect of Hemodialysis Modality and New Anti-glycemic Drugs on NETosis on in Hemodialysis and Diabetic Patient, and Assessment of NETosis in Various Kidney Diseases
- ClinicalTrials.gov ID
- NCT06821919
- Acronym / sponsor ID
- NETs / 0108-22-NHR
- Conditions
- Diabetes Mellitus, Kidney Disease
- Keywords
- NETosis, Diabetes mellitus, kidney disease, glomerulonephritis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Western Galilee Hospital-NahariyaOther government
- Study start
- 13 May 2024 (actual)
- Primary completion
- 30 Dec 2030 (estimated)
- Study completion
- 30 Dec 2031 (estimated)
- First posted
- 12 Feb 2025 (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.
This study aims to investigate whether new glucose-lowering medications, such as SGLT2 inhibitors (e.g., Forxiga/Jardiance) and GLP-1 receptor agonists (e.g., Ozempic), can reduce NETosis in diabetic patients, thereby mitigating secondary complications such as cardiovascular disease and kidney damage. By targeting dysregulated NET formation, the study seeks to establish a link between reduced NETosis and improved clinical outcomes in diabetes.
Additionally, the study will evaluate the effects of immunosuppressive therapies on NETosis in patients with immune-mediated kidney diseases, such as ANCA-associated vasculitis. By correlating NETosis activity with disease progression and treatment response, this research will assess whether reducing NETosis contributes to better management of inflammation and secondary morbidity in these conditions.
Through these evaluations, the study aims to identify potential therapeutic strategies to improve outcomes in both diabetic and chronic kidney disease populations.
Detailed description
Neutrophil extracellular traps (NETs) are an essential component of the innate immune system, designed to trap and neutralize invading pathogens. NETosis, the process by which neutrophils release decondensed chromatin (DNA and histones) decorated with antimicrobial proteins such as myeloperoxidase (MPO) and neutrophil elastase (NE), is a critical mechanism in host defense. This process is induced by stimuli such as PMA, antibodies, cytokines, chemokines, and sterile triggers, including high glucose, cholesterol, and hypoxia. This stimulation activates the Raf-MEK-ERK pathway and NADPH oxidase-dependent production of reactive oxygen species.1,2 An increase in cytosolic calcium cations activates NADPH oxidases and acts as a cofactor for peptidylarginine deiminase 4 (PAD4). PAD4 catalyzes citrullinated histone H3 (Cit-H3) inducing chromatin decondensation, resulting in a cell extrusion of mixture of DNA and bactericidal proteins, including MPO and NE, which all serves as a specific markers of NETosis.1,2 While beneficial in infection settings, excessive or dysregulated NET formation can cause significant tissue damage and organ dysfunction. NETs have been implicated in the pathogenesis of various acute and chronic inflammatory diseases, including myocardial infarction, atherosclerosis, autoimmune diseases, diabetes, and chronic kidney disease (CKD). Elevated NETosis markers, including cell-free DNA (cfDNA) and Cit-H3, are commonly observed in these conditions, underscoring their role in disease progression.3 Given the dual nature of NETosis, understanding how different factors influence this process is critical for developing targeted therapies. This study focuses on two key aspects: evaluating the effects of antiglycemic medications on NETosis and investigating NETosis across different stages of immune-mediated kidney disease before and after immunosuppressive therapy.
(The hemodialysis part of this trial is not included in the current protocol)
Part 1: Evaluating the Effects of Antiglycemic Medications on NETosis Dysregulated NETosis in diabetic and CKD patients contributes to systemic inflammation and organ damage. Studies have shown elevated levels of NETosis markers, such as cfDNA and Cit-H3, in these populations. While metformin has demonstrated the ability to reduce NET formation in diabetic patients, the effects of newer glucose-lowering agents, including SGLT2 inhibitors and GLP-1 receptor agonists, remain unexplored.4 Both SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated robust cardiovascular and renal protective effects.5 This study aims to evaluate their impact on basal and stimulated NETosis in diabetic and CKD patients with various etiologies. By analyzing NETosis markers before and after treatment, this research will provide insights into whether these agents can modulate NETosis, thereby offering additional anti-inflammatory benefits and reducing disease-associated complications.
Part 2: Evaluating NETosis at Different Stages of Immune-Mediated Kidney Disease and After Immunosuppressive Therapy Immune-mediated kidney diseases, such as ANCA-associated vasculitis, involve heightened NETosis that contributes to kidney injury and systemic inflammation.2 Chronic kidney disease resulting from these conditions often exhibits elevated NET formation, exacerbating disease progression. This study seeks to investigate the dynamics of NETosis at various stages of CKD caused by immune-mediated diseases.
In addition, the effects of immunosuppressive therapy on NETosis will be assessed. Immunosuppressive medications, a cornerstone in the treatment of diseases like ANCA-associated vasculitis, can influence neutrophil activity. By monitoring NETosis markers, including cfDNA, Cit-H3, MPO, and NE, before and after initiating immunosuppressive therapy, the study aims to identify patterns of response and the potential therapeutic modulation of NETosis.
Conclusion This comprehensive investigation into the effects of antiglycemic medications and immunosuppressive therapy on NETosis will provide critical insights into the interplay between treatment, inflammation, and disease progression in diabetic and CKD patients. These findings may help pave the way for targeted interventions aimed at modulating NETosis and improving outcomes in high-risk populations.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Diabetes mellitus patients | – | –2. Diabetic Patients (DM Therapy Study) * Sample Size: 20 diabetic patients. * Group 1: 10 patients treated with Forxiga/Jardiance (SGLT2 inhibitors). * Group 2: 10 patients treated with Ozempic (GLP-1 agonist). * Patient Criteria: o Patients naïve to SGLT2 inhibitors and GLP-1 receptor agonists to ensure the observed effects are attributable to the initiation of these therapies. * Sample Collection: * Serum samples (6 ml in serum separator tubes). * Two tubes (12 ml total) will be collected per participant at each time point: Before starting treatment and at 1, 2, 3, 6, and 12 months after initiating medication. * Inclusion Criteria: * Diabetic patients aged 18 years or older (men and women). * Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. * Exclusion Criteria: * Patients with conditions affecting NETosis, including autoimmunity, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. |
| Chronic kidney disease (CKD) patients | – | –Chronic Kidney Disease (CKD) Patients (Evaluation of Immunosuppressive Therapy) * Sample Size: 50 CKD patients with various etiologies. * Focus: o This part of the study will specifically evaluate immune-mediated kidney disease, such as ANCA-associated vasculitis, and the effects of immunosuppressive therapy on NETosis. * Objective: * Assess NETosis markers (e.g., cfDNA, Cit-H3, MPO, NE) before initiating immunosuppressive treatment and at 1, 2, 3, 6, and 12 months of therapy. * Correlate NETosis dynamics with clinical variables, including disease activity, renal function, and inflammatory markers. * Sample Collection: o Serum samples (6 ml in serum separator tubes). o Two tubes (12 ml total) will be collected per participant at each time point: Before starting treatment and at 1, 2, 3, 6, and 12 months after initiating medication. * Exclusion Criteria: * Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. |
| 10 healthy participants will be recruited to the control group (for both studies). | – | –Control Group * Sample Size: 10 healthy participants. * Objective: o Serve as controls for both the diabetic and CKD studies. * Sample Collection: * Two tubes (12 ml total) will be collected per participant * Eligibility: * Healthy individuals without underlying medical conditions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- DM therapy study: - Diabetic patients aged 18 years or older (men and women). * Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. • Exclusion Criteria: * Patients with conditions affecting NETosis, including autoimmunity, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. Chronic kidney disease (CKD) patients :This study will include 50 CKD patients with various etiologies, with a focus on those with immune-mediated kidney diseases, such as ANCA-associated vasculitis. The primary aim is to evaluate the effects of immunosuppressive therapy on NETosis. All patients will be naïve to prior immunosuppressive therapy to ensure the observed effects are directly attributable to the initiation of treatment. • Exclusion Criteria: o Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
Key inclusion criteria (7 listed)
- DM therapy study: - Diabetic patients aged 18 years or older (men and women).
- Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists.
- -Chronic kidney disease (CKD) patients :50 CKD patients with various etiologies.
- This part of the study will specifically evaluate immune-mediated kidney disease, such as ANCA-associated vasculitis, and the effects of immunosuppressive therapy on NETosis.
- Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
Key exclusion criteria (0 listed)
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
NETosis marker- citrullinated histone H3 (citH3)
Time frame: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
* NETosis markers: NET formation will be assessed in sera blood samples across all groups. * Focus on Naïve Patients: Emphasis will be placed on evaluating the initial effects of antiglycemic medications in diabetic patients and the impact of immunosuppressive therapy in CKD patients with immune-mediated diseases. * Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 and citrullinated histone H3 (citH3) will be quantified using the Citrullinated Histone H3 ELISA Kit: O.D. (501620; Cayman Chemical, Ann Arbor, USA).
NETosis marker- Myeloperoxidase
Time frame: Before treatment, 1,2,3,6 and12 moths after treatment.
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 . MPO measurement will be conducted using Myeloperoxidase ELISA Kit , ng/ml (501410; Cayman Chemical).
NETosis marker- Neutrophil elastase (NE)
Time frame: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 , and NE measurement will be conducted using Human Neutrophil Elastase ELISA Kit, ng/ml (ab204730; Abcam
NETosis marker: Peptidylarginine deiminase 4-PAD4
Time frame: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 and PAD4 measurement will be conducted using (PADI4 ELISA Kit, ng/ml (ELH-PADI4, RayBiotech) according to the manufacturer's instructions
4 secondary outcomes
Kidney function
Time frame: Before treatment, 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy.
Urine protein/ creatinine ratio
Time frame: Before treatment, 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
Major adverse cardiovascular events (MACE)
Time frame: 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
All cause mortality
Time frame: 1,2 , 3, 6 and 12 months, and each year (during 5 years) after starting anti-diabetic drugs or immunosuppression therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Individual participant dataSharing planned: Yes. All anonymized data collected during the study will be made available upon reasonable request. This ensures transparency and allows for independent validation of the findings while protecting participant privacy. Identifiable information will be removed, and data will only be shared in a de-identified format, ensuring that participants cannot be traced back based on the shared data. Access to the anonymized dataset will require approval from the principal investigator to ensure appropriate use and adherence to ethical standards.
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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.
Olga Vdovich, MD contact
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 Diabetes Mellitus and Kidney Disease, run by Western Galilee Hospital-Nahariya at 1 site in Israel.
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 0 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: looking for participants now, as of the sponsor's last update on 12 Feb 2025. 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 Israel. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Etty Kruzel-Davila, MD (972-4-9107619, ETTYK@gmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NETosis marker- citrullinated histone H3 (citH3) (time frame: Before treatment, 1,2 , 3, 6 and 12 months after starting anti-diabetic drugs or immunosuppression). The study lists 4 primary outcomes in all. 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 12 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.