The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis
Primary Purpose
Autoimmune Hepatitis
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Low Salt Diet
Liberal salt diet
Sponsored by
About this trial
This is an interventional basic science trial for Autoimmune Hepatitis focused on measuring Autoimmune hepatitis, Liver dysfunction, Elevated serum auto antibodies
Eligibility Criteria
Inclusion Criteria:
- Adults 18-50 years of age
- Children 1-17 years of age
- ALT and/or ALP/GGT level > 2X upper limit of normal
- ANA or SMA >/= 1:40
- ANA or SMA >/= 1:80
- or LKM >/= 1:40
- or SLA positive
- IgG > upper limit of normal
Exclusion Criteria:
- Chronic hepatitis C
- Decompensated Liver Disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low salt/ Liberal salt Diet
Liberal salt/Low salt diet
Arm Description
Cross-over trial of liberal salt and low salt diet.
Cross-over trial of low salt and liberal salt diet
Outcomes
Primary Outcome Measures
Change from baseline in production of pathogenic TH17 cells.
Measuring TH17 cells by flow cytometry and qRT-PCR. There are no known normal ranges. The investigator will calculate the change by observing the difference from baseline values.
Secondary Outcome Measures
Change from baseline in regulatory T cell function.
Measuring T cell function by flow cytometry. There are no known normal ranges. The investigator will calculate the change by observing the difference from baseline values.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02050646
Brief Title
The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis
Official Title
The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 27, 2013 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
June 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether a salt restriction diet improves immune parameters in patients with autoimmune hepatitis.
Detailed Description
The etiology of autoimmune hepatitis (AIH) is unknown although both genetic and environmental factors are thought to be involved. A defect in immune regulation affecting regulatory T cells (Tregs) has been demonstrated in AIH. Tregs function in the maintenance of immune homeostasis by controlling autoreactive immune responses to self-antigens.
Rationale: the western diet has been postulated as a potential environmental risk factor for the increasing incidence of autoimmune diseases in developed countries. Data from the investigators' laboratory also suggests that increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic Th17 cells. The dramatic in vitro effects of high salt on the induction of pathogenic Th17 cells from naïve human CD4 cells {Kleinewietfeld, Hafler. Nature. 2013 Apr 25;496(7446):518-22. doi: 10.1038/nature11868.}, and block of in vitro Treg suppression, in line with in vivo effects on worsening murine experimental autoimmune encephalomyelitis (EAE), have prompted the investigators to examine the effects of increased dietary sodium chloride in a human in vivo system.
The investigators hypothesize that excess dietary salt may function as an environmental trigger that favors induction and expansion of pathogenic Th17 cells and leads to functional impairment of Tregs, thereby favoring development of autoimmunity. The investigators aim to study their established in vitro model in humans by altering the salt intake in patients over a 20-day period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Hepatitis
Keywords
Autoimmune hepatitis, Liver dysfunction, Elevated serum auto antibodies
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Care ProviderInvestigator
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low salt/ Liberal salt Diet
Arm Type
Experimental
Arm Description
Cross-over trial of liberal salt and low salt diet.
Arm Title
Liberal salt/Low salt diet
Arm Type
Experimental
Arm Description
Cross-over trial of low salt and liberal salt diet
Intervention Type
Other
Intervention Name(s)
Low Salt Diet
Intervention Description
On Day 0, patients will be randomized to one of the two crossover liberal/low or low/liberal salt diet groups. Each subject will complete two controlled dietary phases: 10-days of low salt diet, a washout period of 3-days, and 10-days of liberal salt diet.
Intervention Type
Other
Intervention Name(s)
Liberal salt diet
Intervention Description
On Day 0, patients will be randomized to one of the two crossover liberal/low or low/liberal salt diet groups. Each subject will complete two controlled dietary phases: 10-days of low salt diet, a washout period of 3-days, and 10-days of liberal salt diet.
Primary Outcome Measure Information:
Title
Change from baseline in production of pathogenic TH17 cells.
Description
Measuring TH17 cells by flow cytometry and qRT-PCR. There are no known normal ranges. The investigator will calculate the change by observing the difference from baseline values.
Time Frame
26 days
Secondary Outcome Measure Information:
Title
Change from baseline in regulatory T cell function.
Description
Measuring T cell function by flow cytometry. There are no known normal ranges. The investigator will calculate the change by observing the difference from baseline values.
Time Frame
26 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adults 18-50 years of age
Children 1-17 years of age
ALT and/or ALP/GGT level > 2X upper limit of normal
ANA or SMA >/= 1:40
ANA or SMA >/= 1:80
or LKM >/= 1:40
or SLA positive
IgG > upper limit of normal
Exclusion Criteria:
Chronic hepatitis C
Decompensated Liver Disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Udeme Ekong, MD, MPH
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis
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