Diabetic Kidney Disease (DKD)
Conditions
Keywords
Dendritic Cell, Immunotherapy, Diabetic Kidney Disease, Cellular Therapy, Autologous
Brief summary
The goal of this single-arm, open-label clinical trial is to evaluate the effects of subcutaneous autologous dendritic cell (DC) and lymphocyte administration on albuminuria and endothelial dysfunction in Type 2 Diabetes Mellitus (T2DM) patients with Diabetic Kidney Disease (DKD). The main questions it aims to answer are: * Does autologous DC immunotherapy reduce urine albumin-creatinine ratio (UACR) in DKD patients? * What are the underlying mechanisms (modulation of inflammation, endothelial dysfunction, angiogenesis, fibrosis, and structural changes) through which DC immunotherapy reduces UACR in DKD patients? Participants will: * Undergo collection of autologous dendritic cells, which will be matured ex vivo using SARS-CoV-2 S protein. * Receive a single subcutaneous injection consisting of matured dendritic cells and lymphocyte reinfusion. * Have UACR measured at baseline and at weeks 1, 2, 3, and 4 post-immunotherapy. * Undergo assessments of other laboratory parameters and kidney imaging (ultrasonography and/or magnetic resonance imaging) at baseline and week 4 post-treatment. * What is the effect of autologous DC immunotherapy on knee OA, assessed by radiographic changes (x-ray) and patient-reported outcomes (WOMAC score)? Additionally, a subgroup of subjects who had neuropathy as comorbidity will be assessed using Electromyography (EMG) and the Toronto Clinical Neuropathy Scale (TCNS). These assessments aimed to determine the impact of the intervention on peripheral nerve function, clinical neuropathy symptoms over the study period. Another subgroup of subjects who had knee osteoarthritis will be assessed their knee x-ray and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score. These assessments aimed to determine the impact of the intervention on knee anatomic structure, function, and pain.
Interventions
BIOLOGICALDendritic cell immunotherapy
DCL (Dendritic Cells+Lymphocytes) previously matured with S-Protein of SARS-CoV-2. The number of cells given depends on individual yields.
Sponsors
Rumah Sakit Pusat Angkatan Darat Gatot Soebroto
Universitas Prima Indonesia
Universitas Pertahanan Indonesia
PT. JES Kasih Nusantara Sejahterah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects that fulfilled the enrollment criteria were given a single dose of autologous DC therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female over 18 years old 2. Understands and agrees to comply with study procedures by providing written informed consent. 3. In the investigator's judgment, the subject is able and willing to comply with study procedures. 4. In the investigator's judgment, the subject is in generally good physical and mental health. This includes the following factors: * Age \> 65 years * Mild to moderate obesity (BMI 30 to 40) * Controlled hypertension with medication * Controlled hyperlipidemia with medication * Mild chronic lung disease * Previously diagnosed with cancer and in remission for at least 1 year 5. Meets the diagnostic criteria for Type 2 Diabetes Mellitus (DM) according to Indonesia's Endocrinology Society (PERKENI) 2021. 6. eGFR ≥ 30 mL/min/1.73 m². 7. Urinary albumin-creatinine ratio (UACR) ≥ 30 mg/g.
Exclusion criteria
1. Receiving immunosuppressive treatments such as corticosteroids, hydroxychloroquine, methotrexate, cyclophosphamide, and others within the last 4 weeks. 2. Known to have other kidney diseases (e.g., polycystic kidney disease, lupus nephritis, ANCA-associated vasculitis, etc.). 3. Known to have other conditions that can cause albuminuria (e.g., myeloma, rhabdomyolysis, paroxysmal nocturnal hemoglobinuria, orthostatic albuminuria, etc.). 4. Diagnosed with other types of diabetes (Type 1 DM, gestational DM, or other forms of DM). 5. Positive pregnancy test. 6. Known to have immunodeficiency diseases such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV); no blood testing required. 7. Requires oxygen supplementation. 8. Diagnosed with invasive cancer and currently receiving anti-cancer therapy, except for hormonal therapy for breast or prostate cancer. 9. History of thromboembolism or a genetic predisposition to thromboembolism, or currently on anti-thromboembolic therapy other than low-dose aspirin. 10. Physical or mental disabilities preventing normal daily activities. 11. In the investigator's judgment, any illness or medical condition that may hinder the subject's participation, including acute, subacute, intermittent, or chronic diseases that could place the subject at risk of injury, prevent compliance with the study protocol, or interfere with study assessments. 12. Measurable parameters include: * Severe obesity: BMI \> 40 * Uncontrolled hypertension: systolic \>180 mmHg, diastolic \>100 mmHg 13. Unwilling to sign the written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine Albumin-Creatinine Ratio (UACR) from Baseline | From baseline to 4 weeks after treament | UACR were evaluated at a total 5 time points: baseline, week 1, 2, 3, and 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in interleukin-10 | From baseline to 4 weeks after treament | Interleukin-10 (IL-10), an inflammatory biomarker, was evaluated at both baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
| Change in intercellular adhesion molecule | From baseline to 4 weeks after treament | Change in intercellular adhesion molecule (ICAM), an endothelial biomarkers, were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in ng/mL. |
| Change in vascular cell adhesion protein | From baseline to 4 weeks after treament | Change in vascular cell adhesion protein (VCAM), an endothelial biomarkers, were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in ng/mL. |
| Change in kidney perfusion | From baseline to 4 weeks after treament | Doppler Ultrasonography (Doppler USG) of the kidneys were performed at baseline and 4 weeks post-treatment. |
| Change in kidney tissue and function | From baseline to 4 weeks after treament | Magnetic Resonance Imaging Diffusion Weighted Imaging (MRI DWI) of the kidneys were performed at baseline and 4 weeks post-treatment. |
| Change in Estimated Glomerular Filtration Rate | From baseline to 4 weeks after treament | Estimated glomerular filtration rate (eGFR) calculated from serum creatinine using the CKD-EPI equation. |
| Change in Angiogenesis Biomarker | From baseline to 4 weeks after treament | An angiogenesis biomarker, vascular endothelial growth factor (VEGF) were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
| Change in Interleukin-6 | From baseline to 4 weeks after treament | Interleukin-6 (IL-6), an inflammatory biomarker, was evaluated at both baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
| Change in tumor necrosis factor-α | From baseline to 4 weeks after treament | Tumor necrosis factor-α (TNF-α), an inflammatory biomarker, was evaluated at both baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
| Change in transforming growth factor-β | From baseline to 4 weeks after treament | Transforming growth factor-β (TGF-β), an endothelial biomarkers, were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
| Change in matrix metalloproteinase-9 | From baseline to 4 weeks after treament | Change in matrix metalloproteinase-9 (MMP-9), an endothelial biomarkers, were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in ng/mL. |
| Change in endhotelin | From baseline to 4 weeks after treament | Endhotelin, an endothelial biomarkers, were evaluated at baseline and 4 weeks post-treatment. With measurements expressed in pg/mL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Knee X-ray | Baseline and 4 weeks after intervention | Knee X-ray done on both knee and graded using Kellgren-Lawrence grading system |
| The Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Baseline to 4 weeks after intervention | The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a self-administered questionnaire for assessing pain, stiffness, and physical function in individuals with osteoarthritis of the hip or knee. The WOMAC is a 24-item tool that includes 5 questions on pain, 2 on stiffness, and 17 on physical function, with higher scores indicating worse symptoms. |
| Change in Nerve Conduction Velocity | From baseline to 4 weeks after treament | Changes in Nerve Conduction Velocity (m/s) as measured by Electromyography were conducted only on a subgroup of patients who had Neuropathy as a comorbidity and were assessed at two time points: baseline and 4 weeks post-treatment. |
| Change in Toronto Clinical Neuropathy Score | From baseline to 4 weeks after treament | Changes in Toronto Clinical Neuropathy Score (TCNS) were conducted only on a subgroup of patients who had Neuropathy as a comorbidity and were assessed at two time points: baseline and 4 weeks post-treatment.This scale is used to assess the severity of diabetic peripheral neuropathy. The score ranges from 0 to 15, with higher scores indicating worse neuropathy. It evaluates various clinical signs, such as the presence of symptoms like pain, numbness, and weakness, along with physical examination findings like ankle reflexes and vibration sensation. A higher score suggests more severe neuropathy and a worse outcome for the patient. |
Countries
Indonesia
Outcome results
None listed