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

NCT02409940 | Unknown Phase 1 DMC

• 1 other identifier: IFA-LSBM-11
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Transplant Rejection

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Autologus Mesenchymal Stem Cells

EXPERIMENTAL

This group would get two doses of mesenchymal stem cell (MSCs) infusion, one day pre transplant and 30 days post transplant. These MSCs would be derived from transplant recipient's bone marrow which are cultured in GMP compliant laboratories for 4-6 weeks.

Biological: Mesenchymal Stem Cells

Allogeniec Mesenchymal Stem Cells

ACTIVE COMPARATOR

This group would get two doses of mesenchymal stem cell (MSCs) infusion, one day pre transplant and 30 days post transplant. These MSCs would be derived from transplant donor's bone marrow which are cultured in GMP compliant laboratories for 4-6 weeks.

Biological: Mesenchymal Stem Cells

Control without Mesenchymal Stem Cells

NO INTERVENTION

This group would get no stem cell infusion.

Interventions

Mesenchymal Stem Cells BIOLOGICAL

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

Also known as: Mesenchymal Stromal Cells

Allogeniec Mesenchymal Stem Cells; Autologus Mesenchymal Stem Cells

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Translational and Regenerative Medicine

Chandigarh, Chandigarh, 160012, India

Location

Related 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.

  PMID: 25230334 BACKGROUND

• 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.

  PMID: 25173397 BACKGROUND

Study Officials

• Aruna Rakha, PhD.

  PGIMER, Chandigarh, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DST Inspire Faculty

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: April 7, 2015
• Study Start: September 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: March 1, 2017
• Last Updated: November 8, 2016

Record last verified: 2016-11

Locations

IN (1)