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

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ClinicalTrials.gov Identifier: NCT02050646
Recruitment Status : Recruiting
First Posted : January 31, 2014
Last Update Posted : January 9, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

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

Condition or disease Intervention/treatment
Autoimmune Hepatitis Other: Low Salt Diet Other: Liberal salt diet

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: The Role of Sodium Chloride and the Treg/Th17 Axis in Autoimmune Hepatitis
Study Start Date : April 2013
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Low salt/ Liberal salt Diet
Cross-over trial of liberal salt and low salt diet.
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.
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.
Experimental: Liberal salt/Low salt diet
Cross-over trial of low salt and liberal salt diet
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.
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.



Primary Outcome Measures :
  1. Change from baseline in production of pathogenic TH17 cells. [ Time Frame: 26 days ]
    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 :
  1. Change from baseline in regulatory T cell function. [ Time Frame: 26 days ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02050646


Locations
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Udeme Ekong, MD, MPH    203-785-4649    udeme.ekong@yale.edu   
Contact: Lisa Nichols, BA    203-785-7526    lisa.nichols@yale.edu   
Principal Investigator: Udeme Ekong, MD, MPH         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Udeme Ekong, MD, MPH Yale University

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02050646     History of Changes
Other Study ID Numbers: 1303011696
YSOM Pediatrics Department ( Other Identifier: Yale University School of Medicine )
First Posted: January 31, 2014    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Keywords provided by Yale University:
Autoimmune hepatitis
Liver dysfunction
Elevated serum auto antibodies

Additional relevant MeSH terms:
Hepatitis, Autoimmune
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatitis, Chronic
Autoimmune Diseases
Immune System Diseases