To Elucidate the Effect of Mesenchymal Stem Cells on the T Cell Repertoire of the Kidney Transplant Patients

Renal Transplant Rejection Clinical Trial

Official title:

A Randomized Trial to Elucidate Effect of Mesenchymal Stem Cells on Immune Modulation in Living Related Kidney Transplant Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02409940
• Other study ID #: IFA-LSBM-11
• Status: Active, not recruiting
• Phase: Phase 1
• First received: March 24, 2015
• Last updated: November 7, 2016
• Start date: September 2013
• Est. completion date: March 2017

Study information

• Verified date: November 2016
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Science and Technology
• Study type: Interventional

Clinical Trial Summary

Despite being a miracle of modern medicine, solid organ transplant recipients are always at risk of rejection, and remain dependent on lifelong immunosuppression. Currently used immunosuppressive drugs suppress the potential of immune system and interfere with the metabolism of medications. Cellular therapies currently being investigated for this purpose require the use of ablative radiotherapy. The investigators are using a less toxic strategy by harnessing the immunosuppressive potential of the MSCs in the Kidney Transplant (KTx) recipients and studying immunomodulation mediated by these cells in the KTx patients.

Hypothesis MSCs interfere with signalling of Immune cells like T cells, B cells and Dendritic cells which leads to improve graft survival of renal transplant patients.

Aim To investigate effect of MSCs on immune cell repertoire in a donor specific mediated response.

The investigators aim to collect peripheral blood from 30 patients (10 patients for autologous cell infusion and 10 for allogeneic (donor derived cell infusion) at various time intervals following MSC therapy. 10 patients serve as controls on standard dose of drugs but without MSC infusion. This peripheral blood would be utilized for isolation of mononuclear cells and performing various immune assays on these cells in a donor specific response.

Description:

This is an open label type of study having 3 groups of patients: 1st group comprising of patients that would undergo allogeneic (donor-derived) mesenchymal stem cell infusion, 2nd group that would undergo autologous (patient-derived) mesenchymal stem cells and the third group (control group) without any stem cell infusion. All the three groups would have standard dose of Immunosuppressive drugs. Initially the investigators want to recruit 10 patients in each group and would increase the group size if the investigators get promising results on the follow up. The investigators plan to follow up the patients upto 1-2 years for immune based assays and then continue the follow up for atleast 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 17
• Est. completion date: March 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• All the renal transplant recipients participating in the trial should undergo primary kidney transplant.

• Donor should be living and related to the patient.

• Kidney transplant recipients and donor should be willing to give informed consent form.

Exclusion Criteria:

• There should be no prior sensitization to the patients.

• Patients should not be participating in any other study

• Patients should not be suffering from any autoimmune disorders.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Renal Transplant Rejection

Intervention

Biological:
• Mesenchymal Stem Cells
These Mesenchymal stem cells are derived from bone marrow of either renal transplant patients or their donors depending upon the group of study.

Locations

Country	Name	City	State
India	Translational and Regenerative Medicine	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (2)

Mudrabettu C, Kumar V, Rakha A, Yadav AK, Ramachandran R, Kanwar DB, Nada R, Minz M, Sakhuja V, Marwaha N, Jha V. Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study. Nephrology (Carlton). 2015 Jan;20(1):25-33. doi: 10.1111/nep.12338. — View Citation

Rakha A, Todeschini M, Casiraghi F. Assessment of anti-donor T cell proliferation and cytotoxic T lymphocyte-mediated lympholysis in living donor kidney transplant patients. Methods Mol Biol. 2014;1213:355-64. doi: 10.1007/978-1-4939-1453-1_29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expansion of regulatory T cell compartment of the patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		6 months	No
Primary	Normalization of serum creatinine levels of the patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		6 months	No
Secondary	T cell proliferation changes in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation	No
Secondary	Changes in regulatory T cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation	No
Secondary	Changes in memory T cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation	No
Secondary	Changes in B cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation	No
Secondary	Changes in cytokine profile in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients.		0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation	No