Salt and TH-17 in Healthy Human Subjects

June 4, 2021 updated by: Gordon H. Williams, MD, Brigham and Women's Hospital

Evaluation of the Influence of Salt Intake on TH17 Interleukin(IL)-17 Producing CD4+ Helper T Cells in Human Subjects

The overall goal of this study is to evaluate the association between sodium and TH17 cells in human subjects. The subjects will have levels of TH-17 and various hormones measured on low salt diet, low salt diet with intravenous normal saline, and high salt diet.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

In recent years, dietary sodium intake has dramatically increased and has been shown to play an active role in a number of detrimental diseases including hypertension and cardiovascular complications. Additionally, in the developed world, there has been a steady increase in autoimmune diseases. Type 17 helper T cells (Th17) have been shown to play an active role in the development of autoimmune diseases.

Serum glucocorticoid kinase (SGK1) has been shown to influence sodium transport and salt homeostasis in many cell types (Wulf, J. Clin. Invest. 2002; Salker, Nature Med 2011). Prior in vitro and in vivo studies have shown that an increase in salt concentration in the media or dietary salt intake in mice induces SGK1 expression and enhances TH17 cell differentiation and worsens experimental autoimmune encephalomyelitis (EAE), animal model for multiple sclerosis (Kleinewietfeld, Nature 2013; Wu, Nature 2013).

The findings in this study can substantially increase the investigators understanding of environmental factors that modulate the development of autoimmunity in humans. In animal models the worsening effects of a high salt diet on EAE are dramatic. To the investigators knowledge, the proposed study will be the first to determine if salt intake has the same adverse impact in humans. If documented, one could envision the development of a novel treatment approach for human autoimmunity via the regulation of salt intake. Thus, the overall goal of this study is to evaluate the association between sodium and TH17 cells in human subjects. In addition to measuring TH17 cells by flow cytometry the investigators will also measure interleukins such as IL-17a, IL-17f, IL-23 that are important in TH17 differentiation and production.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • We will seek normal, healthy volunteers age 18-45 years. Participants must be healthy, BMI 18-25.
  • We will first recruit male subjects into the pilot study to fully assess the relationship between immune status and salt intake in the absence of hormonal influences (ovulation and menstruation) to establish a baseline understanding before embarking on such a study in women. We will study healthy women subjects in a subsequent later study.

Subjects must have normal laboratory values for:

  1. Complete blood count
  2. Serum creatinine, sodium, potassium, glucose, liver enzymes
  3. Urinalysis
  4. Normal ECG

Exclusion Criteria:

We will exclude individuals with:

  • Systolic blood pressure > 140 or < 90
  • Diastolic blood pressure >90 or < 60
  • Creatinine Clearance is abnormal (MDRD formula)
  • Known DM, CHF, CAD, PVD, CVA, MI, or RAS.
  • Known autoimmune disease (including thyroid disease, asthma, inflammatory bowel disease, rheumatologic diseases)
  • Known neurologic disease (i.e. MS)
  • Steroid use (oral or inhaled, chronic or within the past 6 months)
  • Significant concomitant medical illnesses (cancer, chronic active immunological conditions, etc.)
  • If spot Na > 30 after low salt diet
  • Current excessive etoh (>10oz/etoh/week)
  • Current use of recreational drugs
  • Current smokers
  • Abnormal labs
  • Acute hospitalizations including surgery in the past 6 months
  • Chronic use of non-steroidal anti-inflammatory or narcotic medications
  • Evidence of ischemia or heart block on screening electrocardiogram (greater than type I-second degree heart block, left bundle branch block, or
  • ST-T wave changes in 2 or more contiguous leads)
  • Subjects taking any prescription medications (with the exception of birth control pills) or herbal medications will be excluded).
  • Ingestion of probiotics within last 3 months
  • Antibiotic use within last 3 months
  • 1st degree relative with an onset of diabetes or hypertension before the age of 60
  • 1st degree relative with autoimmune disease (including thyroid disease, asthma, inflammatory bowel disease, rheumatologic diseases)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Subjects in study
All subjects in study are in a cross-over study with 3 interventions sequentially (low salt diet, low salt diet + IV normal saline, liberal salt diet)
Dietary supplement: Low salt diet
Low salt diet, 10mmoL of sodium per day, for 6 days
Dietary supplement: Low salt diet + IV normal saline
Low salt diet, 10 mmoL of sodium per day, for 4 days with normal saline infusion x 12 hours per day for 200 mmoL of sodium chloride. Total daily sodium is 210 mmoL/day.
Dietary supplement: Liberal salt diet
Liberal salt diet targeting 200 mmoL of sodium per day x 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
TH-17 levels
Time Frame: 5 days
5 days

Secondary Outcome Measures

Outcome Measure
Time Frame
IL-17 levels
Time Frame: 5 days
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: Gordon Williams, MD, Brigham and Women's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 1, 2014

Primary Completion (ACTUAL)

July 1, 2019

Study Completion (ACTUAL)

August 1, 2019

Study Registration Dates

First Submitted

October 7, 2014

First Submitted That Met QC Criteria

October 9, 2014

First Posted (ESTIMATE)

October 10, 2014

Study Record Updates

Last Update Posted (ACTUAL)

June 8, 2021

Last Update Submitted That Met QC Criteria

June 4, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013P002358

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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