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

Yale University

Status: Completed

Conditions: Autoimmune Hepatitis

Treatments: Other: Liberal salt diet; Other: Low Salt Diet

Study type: Interventional

Funder types: Other

Identifiers

NCT02050646

1303011696

YSOM Pediatrics Department (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 1 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 2 patient groups

Low salt/ Liberal salt Diet

Experimental group

Description:

Cross-over trial of liberal salt and low salt diet.

Treatment:

Other: Liberal salt diet

Other: Low Salt Diet

Liberal salt/Low salt diet

Experimental group

Description:

Cross-over trial of low salt and liberal salt diet

Treatment:

Other: Liberal salt diet

Other: Low Salt Diet