Use of Erythropoietin to Expand Regulatory T Cells in Autoimmune Liver Disease

This study evaluates the effect of erythropoietin on the number and function of regulatory T cells in adults with autoimmune hepatitis. Participants will receive a single dose of erythropoietin, and then the investigators will collect blood at different time points for analysis of regulatory T cell number and function.

Study Overview

• Status: Completed
• Conditions: Autoimmune Hepatitis
• Intervention / Treatment: Drug: Erythropoietin

Detailed Description

There is data from the laboratory that erythropoietin helps stimulate regulatory T cells, a type of immune cell which is thought to combat autoimmunity, but this study will look at whether it does the same thing in adults with autoimmune hepatitis.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of autoimmune liver diseases (autoimmune hepatitis, autoimmune cholangiopathy, or primary biliary cirrhosis or primary sclerosing cholangitis with hepatic autoimmune liver disease or overlap syndrome) confirmed on liver biopsy
• Use of immunosuppressive therapy (prednisone, azathioprine, 6-mercaptopurine, mycophenolate mofetil) for the treatment of the autoimmune liver disease
• Stable immunosuppression regimen at least 6 months prior to enrollment
• Ability to provide verbal and written informed consent

Exclusion Criteria:

• Diagnosis of decompensated cirrhosis (defined by presence of ascites, varices, encephalopathy)
• Hemoglobin above average normal value (15.7 g/dL in men, 13.8 g/dL in women)
• Alanine aminotransferase greater than 2 times upper limit of normal (33 IU/L in men and 25 IU/L in women)
• Uncontrolled hypertension with systolic blood pressure greater than or equal to 160 or diastolic blood pressure greater than or equal to 100
• End-stage renal disease on hemodialysis
• History of venous thromboembolism including deep vein thromboses or pulmonary emboli
• History of stroke
• History of heart failure
• History of seizure disorder
• History of significant cardiovascular disease including a history of myocardial infarction
• Active malignancy (untreated or undergoing therapy)
• History of pure red cell aplasia
• History of intolerance or allergy to erythropoietin
• Known hypersensitivity to mammalian cell-derived products
• Known hypersensitivity to human albumin
• Presence of vascular access
• Prior recipient of erythropoietin within 12 weeks of the study
• Patient unable to provide consent including infants, children, teenagers, prisoners, cognitively impaired adults
• Non-English speaking
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single arm; Single dose of erythropoietin 10,000 units to be administered subcutaneously at time of enrollment.	Drug: Erythropoietin; Subcutaneous injection of erythropoietin 10,000 units

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of regulatory T cells	Calculated relative to baseline collected at time of enrollment	At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of effector T cells after a single dose of erythropoietin	Calculated relative to baseline collected at time of enrollment	At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.
Change in cytokine production by the T cells in response to ex vivo stimulation	Calculated relative to baseline collected at time of enrollment	At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Icahn School of Medicine at Mount Sinai; Mount Sinai Hospital, New York

Publications and helpful links

General Publications

• McEachern E, Carroll AM, Fribourg M, Schiano TD, Hartzell S, Bin S, Cravedi P, Levitsky J. Erythropoietin administration expands regulatory T cells in patients with autoimmune hepatitis. J Autoimmun. 2021 May;119:102629. doi: 10.1016/j.jaut.2021.102629. Epub 2021 Mar 13. Erratum In: J Autoimmun. 2021 Jul;121:102665.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 25, 2019
• Primary Completion (ACTUAL): February 18, 2021
• Study Completion (ACTUAL): February 18, 2021

Study Registration Dates

• First Submitted: February 12, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (ACTUAL): February 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Autoimmune Diseases; Hepatitis, Chronic; Hepatitis; Liver Diseases; Hepatitis, Autoimmune; Hematinics; Epoetin Alfa
• Other Study ID Numbers: STU00206077

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes