Clinical trial NCT03842254: Use of Erythropoietin to Expand Regulatory T Cells in Autoimmune Liver Disease
Official title: Use of Erythropoietin to Expand Regulatory T Cells in Autoimmune Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Autoimmune Hepatitis
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Mount Sinai Hospital, New York
name: Icahn School of Medicine at Mount Sinai
First posted: 2019-02-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in number of regulatory T cells
timeFrame: At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.
Secondary outcomes:
measure: Change in number of effector T cells after a single dose of erythropoietin
timeFrame: At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.
measure: Change in cytokine production by the T cells in response to ex vivo stimulation
timeFrame: At time of enrollment, then at 2 weeks, 4 weeks, and 12 weeks.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: New York
country: United States
facility: Mount Sinai
state: New York
Study officials:
References:
citation: 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.