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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Biological: Interleukin-2

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Adult liver transplant recipients 2-4 years post transplantation
2. Male or female adult, age 18 - 65 years
3. Stable dosage of suppressant therapy for 1 month prior to study.

Exclusion criteria:

1. Recipient of multiple transplants (including solid organ, stem-cell, and bone marrow)
2. Serum liver panel (ALT, AST, Alkaline Phosphatase and Total Bilirubin) > 2 x ULN,
3. Serum creatinine > 1.5 x ULN,
4. eGFR of < 40 ml/min,
5. Detectable hepatitis viral load,
6. Abnormal ECG with clinically significant findings per study physician's judgement,
7. Active infection,
8. Presence or history of autoimmunity disorders,
9. Evidence of allograft rejection,
10. Liver biopsy or fibroscan evidence of advanced stage liver fibrosis (> Stage 2 Fibrosis),
11. Presence or history of cardiac or pulmonary disease,
12. Pregnant or nursing (lactating) women,
13. Health condition precludes participation in trial at study physician's judgment,
14. Inability to give consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interleukin-2; 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; Subjects will self-administer low dose IL-2 as subQ injection (0.30 MIU per meter squared body surface area) for 4 weeks.; Other Names: Proleukin; Aldesleukin; IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regulatory T-Cell Count	Peripheral Blood Mononuclear Cell Flow Cytometry	baseline, week 2, week 4, week8, week12
% Increase in CD4 Tregs	% CD4 T Regs were measured at several time points after IL-2 administration.	baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential Immune Cell Count	Peripheral Blood Mononuclear Cell Flow Cytometry	baseline, 2 weeks, 4 weeks, 8 weeks, 12 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney Function Serum Panel (> 1.5 x Upper Limit Normal)	Number of participants with a serum creatinine > 1.5 x upper limit of normal through week 36	2 weeks, 4 weeks, 8 weeks, 12 weeks, 36 weeks
Liver Function Serum Panel (> 2 x Upper Limit Normal)	Number of patients with a serum amino alaninetransferase > 2 x upper limit of normal through week 36	week 2, 4 week, week 8, week12, week36

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Michael P Curry, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimated): April 15, 2016

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; Lymphokines; Interleukin-2; aldesleukin
• Other Study ID Numbers: 2016P000086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO