Thymoglobulin: Presence and Affect in the Central Lymphatic Compartment

Sponsor

Swedish Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00714480

Collaborator

Genzyme, a Sanofi Company (Industry)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplantation Immunosuppression	Drug: anti-thymocyte globulin Drug: anti-thymocyte globulin Drug: anti-thymocyte globulin	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Thymoglobulin: Presence and Affect in the Central Lymphatic Compartment

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Group I Administration of anti-thymocyte globulin post-operative days -6,-4,-2, and 0	Drug: anti-thymocyte globulin Administration of anti-thymocyte globulin at post-operative days -6, -4, -2 and 0 Other Names: Thymoglobulin
Other: Group II Administration of anti-thymoglobulin post-operative days -2, 0, 2 and 4	Drug: anti-thymocyte globulin anti-thymocyte globulin post-operative days -2, 0, 2 and 4 Other Names: Thymoglobulin
Other: Group III Administration of anti-thymocyte globulin post-operative days 0, 2, 4 and 6	Drug: anti-thymocyte globulin Post-operative days 0, 2, 4 and 6 Other Names: Thymoglobulin

Arm

Intervention/Treatment

Other: Group I

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

Drug: anti-thymocyte globulin

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

Other Names:

Thymoglobulin

Other: Group II

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

Drug: anti-thymocyte globulin

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

Other Names:

Thymoglobulin

Other: Group III

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

Drug: anti-thymocyte globulin

Post-operative days 0, 2, 4 and 6

Other Names:

Thymoglobulin

Outcome Measures

Primary Outcome Measures

The primary objectives of this pilot study are to examine lymphocyte marker expression, quantitate specific lymphocyte subsets and apoptosis, and assess immune function in subjects receiving TMG. [Pretransplant days -6, -4, -2, 0; Post-transplant days 2, 4, 6]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All subjects age 18 years or older who qualify to receive a living (related or unrelated) kidney allograft using steroid free induction immunosuppression.
Single organ recipient (kidney only)
Subjects receiving first renal transplant
Women of childbearing potential should have a negative serum pregnancy test within 1 week prior to beginning study medications
Subjects with no prior history of immunosuppression
Subjects with no systemic illness (i.e. diabetes, autoimmune disease)
Subjects with negative serologies (Hep B, Hep C, HIV)
Subjects who are candidates for TMG induction
Subjects providing written consent
Subjects who are compliant and able to complete all the assessment procedures