Thymoglobulin: Presence and Affect in the Central Lymphatic Compartment

NCT ID: NCT00714480

Last Updated: 2011-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2009-12-31

Brief Summary

This study proposes to examine the effect of TMG therapy upon the cellular elements within the central (bone marrow) and peripheral (lymph node) lymphoid compartments of humans. Briefly, bone marrow aspirates and lymph nodes will be obtained at the time of transplant, from renal transplant recipients receiving TMG induction therapy. For comparative purposes, peripheral blood samples will also be obtained. Lymphocytes from these compartments will be assessed for CD antigen expression, apoptosis, cytokine production following memory immune responses, and functional assays to assess potential regulatory T-cell (Treg) activity.

Detailed Description

Polyclonal anti-thymocyte globulins are used with increasing frequency to induce immunosuppression in organ transplant recipients. Induction therapy is used for the majority of persons receiving kidney transplant. In 2004, 72% of patients that received a kidney transplant also received induction therapy. This number is up from 46% reported in 1995. Anti-Thymocyte Globulin is the most commonly used agent for induction therapy. It was used for 37% of kidney recipients in 2004, and its use appears to be increasing year over year. A prominent example of this class of drugs is Thymoglobulin(TMG), a purified, pasteurized gamma immune globulin, which is obtained by immunization of rabbits with human thymocytes. The resulting preparation contains polyclonal antibodies directed against multiple T-cell markers, including CD antigens, HLA, and homing receptors.

Although the mechanism of action for the immunosuppressive effects of TMG has not been fully elucidated, there is evidence that complement-dependent cell lysis and depletion, cell-surface antigen modulation, blocking of adhesion molecules, and partial T-cell activation/anergy may play potential roles.

Many of the effects of TMG are evident in the peripheral blood compartment, including a rapid decline in circulating T-cells. Non-human primate studies have demonstrated that TMG treatment leads to depletion of T-cells via apoptosis in peripheral lymphoid tissues (spleen and lymph nodes), but no studies have been conducted to assess the effect of TMG in the bone marrow, and no studies have examined the peripheral lymphoid tissue in humans receiving TMG therapy.

Conditions

Renal Transplantation; Immunosuppression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Group I

Administration of anti-thymocyte globulin post-operative days -6,-4,-2, and 0

Group Type: OTHER

anti-thymocyte globulin

Intervention Type: DRUG

Administration of anti-thymocyte globulin at post-operative days -6, -4, -2 and 0

Group II

Administration of anti-thymoglobulin post-operative days -2, 0, 2 and 4

Group Type: OTHER

anti-thymocyte globulin

Intervention Type: DRUG

anti-thymocyte globulin post-operative days -2, 0, 2 and 4

Group III

Administration of anti-thymocyte globulin post-operative days 0, 2, 4 and 6

Group Type: OTHER

anti-thymocyte globulin

Intervention Type: DRUG

Post-operative days 0, 2, 4 and 6

Interventions

anti-thymocyte globulin

Administration of anti-thymocyte globulin at post-operative days -6, -4, -2 and 0

Intervention Type: DRUG

anti-thymocyte globulin

anti-thymocyte globulin post-operative days -2, 0, 2 and 4

Intervention Type: DRUG

anti-thymocyte globulin

Post-operative days 0, 2, 4 and 6

Intervention Type: DRUG

Other Intervention Names

Thymoglobulin; Thymoglobulin; Thymoglobulin

Eligibility Criteria

Inclusion Criteria

1. All subjects age 18 years or older who qualify to receive a living (related or unrelated) kidney allograft using steroid free induction immunosuppression.

2. Single organ recipient (kidney only)

3. Subjects receiving first renal transplant

4. Women of childbearing potential should have a negative serum pregnancy test within 1 week prior to beginning study medications

5. Subjects with no prior history of immunosuppression

6. Subjects with no systemic illness (i.e. diabetes, autoimmune disease)

7. Subjects with negative serologies (Hep B, Hep C, HIV)

8. Subjects who are candidates for TMG induction

9. Subjects providing written consent

10. Subjects who are compliant and able to complete all the assessment procedures

Exclusion Criteria

1. Subjects less than 18 years of age

2. Subjects who do not meet criteria for steroid free protocol

3. Subjects who are pregnant, lactating or nursing

4. Child bearing women not willing to use a reliable form of contraception

5. Subjects with a known allergy to rabbits or rabbit products

6. Subjects receiving other medications considered to be experimental

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Swedish Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Swedish Medical Center

Principal Investigators

William H Marks, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Swedish Medical Center

Paul Warner, PhD

Role: PRINCIPAL_INVESTIGATOR

Bloodworks

Locations

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

TMG 617

Identifier Type: -

Identifier Source: org_study_id