Efficacy of Low Dose, SubQ Interleukin-2 (IL-2) to Expand Endogenous Regulatory T-Cells in Liver Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this investigation is to study if very low dose IL-2, given to liver transplant patients by subcutaneous (under the skin) injections, over a 4 week period of time, will cause an increase in the number of Treg cells in the blood.

Detailed Description
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A common complication of organ transplantation is 'rejection' of the transplanted organ. This occurs when the body's immune system tries to attack (or reject) the transplanted organ. Drugs known as immunosuppressants (anti-rejection medications) are prescribed for patients after transplantation to prevent rejection. But, anti-rejection medications are associated with significant side effects including high blood pressure, high blood sugars, and high cholesterol - all of which may increase the risk of heart and vascular complications. Anti-rejection medications also increase the long-term risk of some types of cancer. Sometimes, liver transplant patients who stop taking anti-rejection medications do not experience rejection of their transplanted liver and the liver keeps working. These patients are said to tolerate the transplanted liver, and this condition is referred to as tolerance. Doctors are working to learn more about why some liver transplant patients develop tolerance after receiving a transplant, while others do not. Studies have shown that patients who develop tolerance have an increase in a type of immune cell called regulatory T-cells or Tregs. This means Tregs may be important in preventing rejection of a transplanted organ. Studies have also shown that a human cytokine (a type of protein), called interleukin-2 (IL-2) aids in increasing the number of Treg cells in the body, and IL-2 has been given to patients to successfully treat disorders of the immune system such as graft vs host disease - a serious condition sometimes seen in patients after bone marrow transplantation. The purpose of this investigation is to study if low dose IL-2, given to liver transplant patients by subcutaneous (under the skin) injections, over a 4 week period of time, will cause an increase in the number of Treg cells in the blood. In addition, investigators will learn about the kinds of side effects low dose IL-2 will cause and how severe those side effects will be.

Official Title
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Efficacy of Low Dose, Subcutaneous Interleukin-2 (IL-2) to Expand Endogenous Regulatory T-Cells in Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Biological: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult liver transplant recipients 2-4 years post transplantation Male or female adult, age 18 - 65 years Stable dosage of suppressant therapy for 1 month prior to study. Exclusion criteria: Recipient of multiple transplants (including solid organ, stem-cell, and bone marrow) Serum liver panel (ALT, AST, Alkaline Phosphatase and Total Bilirubin) > 2 x ULN, Serum creatinine > 1.5 x ULN, eGFR of < 40 ml/min, Detectable hepatitis viral load, Abnormal ECG with clinically significant findings per study physician's judgement, Active infection, Presence or history of autoimmunity disorders, Evidence of allograft rejection, Liver biopsy or fibroscan evidence of advanced stage liver fibrosis (> Stage 2 Fibrosis), Presence or history of cardiac or pulmonary disease, Pregnant or nursing (lactating) women, Health condition precludes participation in trial at study physician's judgment, Inability to give consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interleukin-2<br>IL-2 (Interleukin-2; Aldesleukin; Proleukin) administered daily as a single subcutaneous injection 0.30 MIU per meter squared body surface area for a duration of 4 weeks. | Biological: Interleukin-2<br>* Subjects will self-administer low dose IL-2 as subQ injection (0.30 MIU per meter squared body surface area) for 4 weeks.<br>* Other names: Proleukin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regulatory T-Cell Count | Peripheral Blood Mononuclear Cell Flow Cytometry | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differential Immune Cell Count | Peripheral Blood Mononuclear Cell Flow Cytometry | 12 Weeks | 
| T-Cell Exhaustion Phenotyping | Peripheral Blood Mononuclear Cell Flow Cytometry | 1 Day |