Clinical trial NCT06866158: Autologous Dendritic Cell as Adjunct Therapy for Diabetic Kidney Disease
Official title: Single-arm Open-label Clinical Trial: Autologous Dendritic Cells and Lymphocytes in Type 2 Diabetes Mellitus With Albuminuria
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diabetic Kidney Disease (DKD)
Keywords: Dendritic Cell
Immunotherapy
Diabetic Kidney Disease
Cellular Therapy
Autologous
Lead sponsor: PT. JES Kasih Nusantara Sejahterah
Sponsor class: INDUSTRY
Collaborators: name: Rumah Sakit Pusat Angkatan Darat Gatot Soebroto
name: Universitas Prima Indonesia
name: Universitas Pertahanan Indonesia
First posted: 2025-03-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects that fulfilled the enrollment criteria were given a single dose of autologous DC therapy
Primary purpose: TREATMENT

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.

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 and clinical neuropathy symptoms over the study period.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Urine Albumin-Creatinine Ratio (UACR) from Baseline
timeFrame: From baseline to 4 weeks after treament
Secondary outcomes:
measure: Change in Estimated Glomerular Filtration Rate
timeFrame: From baseline to 4 weeks after treament
measure: Change in Angiogenesis Biomarker
timeFrame: From baseline to 4 weeks after treament
measure: Change in Interleukin-6
timeFrame: From baseline to 4 weeks after treament
measure: Change in tumor necrosis factor-α
timeFrame: From baseline to 4 weeks after treament
measure: Change in interleukin-10
timeFrame: From baseline to 4 weeks after treament
measure: Change in transforming growth factor-β
timeFrame: From baseline to 4 weeks after treament
measure: Change in matrix metalloproteinase-9
timeFrame: From baseline to 4 weeks after treament
measure: Change in endhotelin
timeFrame: From baseline to 4 weeks after treament
measure: Change in intercellular adhesion molecule
timeFrame: From baseline to 4 weeks after treament
measure: Change in vascular cell adhesion protein
timeFrame: From baseline to 4 weeks after treament
measure: Change in kidney perfusion
timeFrame: From baseline to 4 weeks after treament
measure: Change in kidney tissue and function
timeFrame: From baseline to 4 weeks after treament
measure: Change in kidney tissue and function
timeFrame: From baseline to 4 weeks after treament
Other outcomes:
measure: Change in Nerve Conduction Velocity
timeFrame: From baseline to 4 weeks after treament
measure: Change in Toronto Clinical Neuropathy Score
timeFrame: From baseline to 4 weeks after treament
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Gatot Soebroto Central Army Hospital
state: DKI Jakarta - Jakarta
Study officials:
affiliation: Gatot Soebroto Central Army Hospital
name: dr Jonny, Sp.PD-KGH, M.Kes, M.M, DCN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jonny J, Sitepu EC, Lister INE, Chiuman L, Putranto TA. The Potential of Anti-Inflammatory DC Immunotherapy in Improving Proteinuria in Type 2 Diabetes Mellitus. Vaccines (Basel). 2024 Aug 27;12(9):972. doi: 10.3390/vaccines12090972.
citation: Setiawan E, Ginting CN, Jonny J, Hernowo BA, Putranto TA. Clinical Trial: Effect of Autologous Dendritic Cell Administration on Improving Neuropathy Symptoms and Inflammatory Biomarkers in Diabetic Neuropathy. Curr Issues Mol Biol. 2024 Dec 20;46(12):14366-14380. doi: 10.3390/cimb46120861.
citation: Dimu PS, Icksan AG, Farhat, Jonny, Hernowo BA, Putranto TA. Clinical Trial of Autologous Dendritic Cell Administration Effect on Water Molecule Diffusion and Anti-Inflammatory Biomarkers in Diabetic Kidney Disease. Curr Issues Mol Biol. 2024 Dec 4;46(12):13767-13779. doi: 10.3390/cimb46120822.
citation: Jonny, Sitepu EC, Hernowo BA, Chiuman L, Lister INE, Putranto TA. Open-Label Clinical Trial on the Impact of Autologous Dendritic Cell Therapy on Albuminuria and Inflammatory Biomarkers (Interleukin-6, Interleukin-10, Tumor Necrosis Factor alpha) in Diabetic Kidney Disease (DKD). Curr Issues Mol Biol. 2024 Dec 2;46(12):13662-13674. doi: 10.3390/cimb46120816.
citation: Yana ML, Sitepu EC, Jonny, Chiuman L, Lister INE, Putranto TA. The Effect of Autologous Dendritic Cell Immunotherapy on Kidney Function and Endothelial Dysfunction of Patients with Diabetic Kidney Disease (DKD): An Open Label Clinical Trial. Curr Issues Mol Biol. 2025 Jan 6;47(1):31. doi: 10.3390/cimb47010031.