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

NCT ID: NCT02050646

Last Updated: 2021-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-27
• Study Completion Date: 2021-06-30

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.

Conditions

Autoimmune Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Low salt/ Liberal salt Diet

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

Group Type: EXPERIMENTAL

Low Salt Diet

Intervention Type: OTHER

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

Intervention Type: OTHER

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/Low salt diet

Cross-over trial of low salt and liberal salt diet

Group Type: EXPERIMENTAL

Low Salt Diet

Intervention Type: OTHER

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

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Udeme Ekong, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Yale University

Other Identifiers

YSOM Pediatrics Department

Identifier Type: OTHER

Identifier Source: secondary_id

1303011696

Identifier Type: -

Identifier Source: org_study_id