The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis

Autoimmune Hepatitis Clinical Trial

Official title:

The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02050646
• Other study ID #: 1303011696
• Secondary ID: YSOM Pediatrics
• Status: Completed
• Phase: N/A
• Start date: August 27, 2013
• Est. completion date: June 2021

Study information

• Verified date: July 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a salt restriction diet improves immune parameters in patients with autoimmune hepatitis.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2021
• Est. primary completion date: August 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Autoimmune

Intervention

Other:
• Low Salt Diet
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.
• Liberal salt diet
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	26 days
Secondary	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.	26 days