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

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ClinicalTrials.gov Identifier: NCT02739412
Recruitment Status : Recruiting
First Posted : April 15, 2016
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Michael Curry, Beth Israel Deaconess Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Liver Transplantation Biological: Interleukin-2 Phase 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Efficacy of Low Dose, Subcutaneous Interleukin-2 (IL-2) to Expand Endogenous Regulatory T-Cells in Liver Transplant Recipients
Study Start Date : November 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Aldesleukin

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:
  • IL-2
  • Aldesleukin
  • Proleukin




Primary Outcome Measures :
  1. Regulatory T-Cell Count [ Time Frame: 12 weeks ]
    Peripheral Blood Mononuclear Cell Flow Cytometry


Secondary Outcome Measures :
  1. Differential Immune Cell Count [ Time Frame: 12 Weeks ]
    Peripheral Blood Mononuclear Cell Flow Cytometry

  2. T-Cell Exhaustion Phenotyping [ Time Frame: 1 Day ]
    Peripheral Blood Mononuclear Cell Flow Cytometry


Other Outcome Measures:
  1. Kidney Function Serum Panel (> 1.5 x Upper Limit Normal) [ Time Frame: 12 weeks ]
    eGFR, creatinine, pH, electrolytes

  2. Liver Function Serum Panel (> 2 x Upper Limit Normal) [ Time Frame: 12 weeks ]
    ALT, AST, AlkPhos, total Bilirubin

  3. Serious Adverse Events (SAEs) [ Time Frame: 12 weeks ]
    Simple absolute counts and frequency



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02739412


Contacts
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Contact: Susan McDermott, RN, MPH 617-632-9841 smcderm2@bidmc.harvard.edu
Contact: Michael P Curry, MD 617.632.9700 mcurry@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susan M McDermott, MPH RN    617-632-9841    smcderm2@bidmc.harvard.edu   
Contact: Michael P Curry, md    617-632-9700    mcurry@bidmc.harvard.com   
Principal Investigator: Michael P Curry, MD         
Sub-Investigator: Terry Strom, MD         
Sub-Investigator: Khalid Khwaja, MD         
Sub-Investigator: Susan M McDermott, MPH RN         
Sub-Investigator: Maria Koulmanda, PhD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Study Director: Terry Strom, MD Beth Israel Deaconess Medical Center

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Responsible Party: Michael Curry, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02739412     History of Changes
Other Study ID Numbers: 2016P000086
First Posted: April 15, 2016    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Interleukin-2
Aldesleukin
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents