Mesenchymal Stem Cell Therapy in Diabetic Kidney Disease-A Double-blind, Placebo-controlled, Randomized Clinical Trial

Diabetes had global prevalence of 9% in 2014 and is increasing alarmingly, affecting approximately 387 million people worldwide. It is strongly linked to complications, like chronic kidney failure, blindness and neurdegeneration. From 1999-2006, prevalence of chronic kidney disease (CKD) stage 1-2 was 11.5%, and stage 3-4 was 58%, while its prevalence in Pakistan is 12.5%. CKD is a pathophysiological process with multiple etiologies, eventually resulting in irreversible nephron damage and leading to End Stage Renal Disease (ESRD), rendering the patient permanently dependent on Renal Replacement. In Pakistan, the prevalence of diabetic ESRD is 22%. Only supportive management is offered, resulting in either dialysis dependency or transplant. High CKD prevalence, renal replacement therapy and associated morbidity-mortality demands more effective and easier treatment option. We propose Mesenchymal Stem Cells (MSC) therapy for reversing the chronic kidney damage caused by type2 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Biological: Mesenchymal stem cells; Drug: Normal Saline (Placebo)

Detailed Description

Diabetes cases increased from 108 million in 1980 to 422 million in 2014 worldwide. Its prevalence has risen more rapidly in low- and middle-income countries than in high-income countries. It has become the leading cause of blindness, kidney failure, heart attacks, stroke and amputation of lower limbs. Damage to kidneys due to high blood is a serious threat, over time they stop the filtration process blood, leading to Chronic Kidney Disease. Approximately 1 in 3 adults with diabetes has CKD, which leads to kidney failure in worst cases and the only options left for the patient are regular dialysis or kidney transplant. Both these options are usually scarce, unaffordable and unavailable in developing countries like Pakistan. In finding an easier and effective treatment option for CKD secondary to diabetes it was found that MSCs can stop tissue damage progression in CKD, this has been extensively investigated in preclinical studies till now. Bone marrow derived MSCs are multipotent, including hematopoietic stem cell, mesenchymal stromal cells and endothelial progenitor cell. MSCs have anti-inflammatory and antifibrotic properties and can suppress maturation, activation and proliferation of T, B and NK cells in vitro and down regulate immune response in vivo. Beneficial effects of MSCs are seen largely through immunomodulatory and paracrine mechanisms like production of growth factors and cytokines with immunosuppressive, anti-inflammatory, anti-apoptotic and proliferative effects. Cultured MSCs release large amounts of pro-angiogenic factor; vascular endothelial growth factor which facilitates glomerular and tubular recovery. MSC therapy in CKD-preclinical studies have shown that single dose of bone marrow-derived MSCs in rats decreased interstitial fibrosis, tubular atrophy, T-cell and macrophage infiltration, and the expression of inflammatory cytokines. This has been attributed to their paracrine immunomodulatory properties rather than long-term engraftment. MSCs also have the capacity to induce proliferation of renal glomerular and tubular cells and increase cellular survival. In preclinical studies injected MSCs secrete pro-angiogenic and trophic factors which enhance proliferation and decrease apoptosis of tubular cells. However, engraftment and trans-differentiation was not observed in the majority of the studies. Although there is a large gap between scientific knowledge and clinical translation for a safe and effective stem cell-based therapy, stem cells hold great promise for the treatment of CKD. We aim to study the efficacy of MSCs treatment in diabetic nephropathy CKD stage 2 and 3 due to type 2 Diabetes Mellitus. For this purpose, we have designed a randomized, double-blinded, placebo-controlled clinical trial to determine the efficacy of MSC therapy in chronic kidney disease.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Rawalpindi, Pakistan, 46000
    • National Institute of Blood and Marrow Transplant (NIBMT), Pakistan/Armed Forces Bone Marrow Transplant Centre
  • Rawalpindi, Pakistan, 46000
    • Pak Emirates Military Hospital, Rawalpindi (PEMH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Male and female patients between 18 and 75 years of age having Type-2 Diabetes with CKD stage 2,3 and 4: (eGFR 15-90 mL/min/1.73 m2).

Exclusion Criteria:

Patients with a history of other comorbidities like previous myocardial infarction, pulmonary disease, pregnant females, unable to follow or return for evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stem cells; Mesenchymal stem cells (30 million cells)	Biological: Mesenchymal stem cells; Mesenchymal stem cells
Placebo Comparator: Normal Saline (Placebo)	Drug: Normal Saline (Placebo); Normal Saline (Placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
isotopic DTPA Scan	Glomerular Filtration Rate using Renal isotope 99mTc-DTPA	To be carried out at enrollment and at six months' post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycosylated Hemoglobin level	Glycosylated Hemoglobin using HBA1c level in blood	To be carried out at baseline and at six months post-intervention

Collaborators and Investigators

• Sponsor: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
• Collaborators: Pak Emirates Military Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: June 18, 2025
• First Submitted That Met QC Criteria: June 18, 2025
• First Posted (Actual): June 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: randomized controlled trial; mesenchymal stem cells; diabetic kidney disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Diabetes Mellitus; Diabetes Complications; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: MSC-CKD/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No