Autologous Dendritic Cell as Adjunct Therapy for Diabetic Kidney Disease

Phase 1

Active, not recruiting

• Conditions: Diabetic Kidney Disease (DKD)
• Interventions: Biological: Dendritic cell immunotherapy

• Registration Number: NCT06866158
• Lead Sponsor: PT. JES Kasih Nusantara Sejahterah

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-01
• Primary Completion: 2024-08-05
• Study First Submitted: 2025-02-22
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-06
• Last Update Submitted: 2025-03-06
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10
• Study Completion: 2025-08-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous DCL	Dendritic cell immunotherapy	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 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.
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 Tensor Imaging (MRI DTI) of the kidneys were performed at baseline and 4 weeks post-treatment.

Trial Locations

Locations (1)

Gatot Soebroto Central Army Hospital; 🇮🇩 Jakarta Pusat, DKI Jakarta - Jakarta, Indonesia