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

Liver Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02739412
• Other study ID #: 2016P000086
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: July 2022

Study information

• Verified date: December 2022
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Kidney Function Serum Panel (> 1.5 x Upper Limit Normal)	eGFR, creatinine, pH, electrolytes	12 weeks
Other	Liver Function Serum Panel (> 2 x Upper Limit Normal)	ALT, AST, AlkPhos, total Bilirubin	12 weeks
Other	Serious Adverse Events (SAEs)	Simple absolute counts and frequency	12 weeks
Primary	Regulatory T-Cell Count	Peripheral Blood Mononuclear Cell Flow Cytometry	12 weeks
Secondary	Differential Immune Cell Count	Peripheral Blood Mononuclear Cell Flow Cytometry	12 Weeks
Secondary	T-Cell Exhaustion Phenotyping	Peripheral Blood Mononuclear Cell Flow Cytometry	1 Day