Effect of Different Therapeutic Strategies on Regulatory T Cells in Kidney Transplantation

NCT01640743 | Completed DMC

• 2 other identifiers: 42501/2009IRCCS Policlinico S. Matteo
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study will be to evaluate the effect of different therapeutic immunosuppressive strategies currently employed in common clinical practice on regulatory T lymphocytes and to verify the hypothesis that the association of thymoglobulins - mTOR inhibitors - small doses of Tacrolimus not only represents a safe anti-rejection therapy but it can also lead to mid-term formation of a high amount of regulatory T cells and, consequently, a high grade of tolerance.

Conditions

Kidney Transplantation

Keywords

Kidney transplantation; Regulatory T cells; Tolerance; Tacrolimus; Rejection

Outcome Measures

Primary Outcomes (1)

• Effect of different treatments on absolute and percentual number of regulatory T cells

  Comparison of absolute and percentual number of high Treg and FoxP3+ Treg cells in one year post-transplant patients under treatment with different immunosuppressive therapies.

  12 months

Secondary Outcomes (1)

• Influence of Treg cell number on renal function and incidence of rejection, death, infection events and cardiovascular diseases.

  24 months

Study Arms (2)

Evertwist 1

EXPERIMENTAL

Tacrolimus (10-14 ng/ml) + Methylprednisolone (16 mg).

Drug: Tacrolimus + Methylprednisolone

Evertwist 2

EXPERIMENTAL

Tacrolimus (4-6 ng/ml) + Everolimus (8-10 ng/ml) + Methylprednisolone (8 mg).

Drug: Tacrolimus + Everolimus + Methylprednisolone

Interventions

Tacrolimus + Methylprednisolone DRUG

Induction therapy: Methylprednisolone (500 mg), thymoglobulins (1.5 mg/Kg/die, beginning 1 hour before transplantation) and 1 mg/Kg/die during the following 3 days. Maintenance therapy: Tacrolimus dosage will be 0.2 mg/kg of body weight and will be administered approximately 12 hours after chirurgical intervention twice a day (mornings and evenings). Dosage will be adapted on individual basis in order to gain pre-dose blood dosages according to indicated plasmatic levels

Evertwist 1

Tacrolimus + Everolimus + Methylprednisolone DRUG

Induction therapy: Methylprednisolone (500 mg), thymoglobulins (2.5 mg/Kg/die, beginning 1 hour before transplant) and Mycophenolate mofetil (1000 mg) and no immunosuppressive therapy for the following 3 days (WOFIE hypothesis), and for day 4-5-6 thymoglobulins (1.0 mg/Kg/die). Maintenance therapy: Tacrolimus dosage will be 0.1 mg/kg of body weight and will be administered approximately 12 hours after chirurgical intervention twice a day (mornings and evenings). Dosage will be adapted on individual basis in order to gain pre-dose blood dosages according to indicated plasmatic levels

Evertwist 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female aged from 18 to 75 years
• Transplanted patients from cadaveric donors
• Patients who has given written informed consensus

You may not qualify if:

• Legally unable patients
• Patients who have been participated to others studies in the last 3 months
• Addicted to alcohol or smoking

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione Policlinico "San Matteo"

Pavia, 27100, Italy

Location

Related Publications (3)

• Taber DJ, Weimert NA, Henderson F, Lin A, Bratton CF, Chavin KD, Baliga PK. Long-term efficacy of induction therapy with anti-interleukin-2 receptor antibodies or thymoglobulin compared with no induction therapy in renal transplantation. Transplant Proc. 2008 Dec;40(10):3401-7. doi: 10.1016/j.transproceed.2008.08.130.

  PMID: 19100399 BACKGROUND

• Riley JL, June CH, Blazar BR. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity. 2009 May;30(5):656-65. doi: 10.1016/j.immuni.2009.04.006.

  PMID: 19464988 BACKGROUND

• Anil Kumar MS, Irfan Saeed M, Ranganna K, Malat G, Sustento-Reodica N, Kumar AM, Meyers WC. Comparison of four different immunosuppression protocols without long-term steroid therapy in kidney recipients monitored by surveillance biopsy: five-year outcomes. Transpl Immunol. 2008 Nov;20(1-2):32-42. doi: 10.1016/j.trim.2008.08.005. Epub 2008 Sep 4.

  PMID: 18773960 BACKGROUND

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Tacrolimus; Methylprednisolone; Everolimus

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sirolimus

Study Officials

• Antonio Dal Canton, MD

  Nephrology Unit, Fondazione Policlinico "San Matteo", Pavia- Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 16, 2012
• Study Start: March 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: April 1, 2014
• Last Updated: March 25, 2015

Record last verified: 2015-03

Locations

IT (1)