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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Autoimmune Hepatitis

Intervention / Treatment
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* Drug: Erythropoietin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Single dose of erythropoietin 10,000 units to be administered subcutaneously at time of enrollment. | Drug: Erythropoietin<br>* Subcutaneous injection of erythropoietin 10,000 units<br>|

What is the study measuring?
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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. |