search
Back to results

Salt and TH-17 in Healthy Human Subjects

Primary Purpose

Th17 Helper Immune Cells, Autoimmunity, Salt Intake

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low salt diet
Low salt diet + IV normal saline
Liberal salt diet
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Th17 Helper Immune Cells

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

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)

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Subjects in study

Arm Description

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)

Outcomes

Primary Outcome Measures

TH-17 levels

Secondary Outcome Measures

IL-17 levels

Full Information

First Posted
October 7, 2014
Last Updated
June 4, 2021
Sponsor
Brigham and Women's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02261688
Brief Title
Salt and TH-17 in Healthy Human Subjects
Official Title
Evaluation of the Influence of Salt Intake on TH17 Interleukin(IL)-17 Producing CD4+ Helper T Cells in Human Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Lack of funds
Study Start Date
March 2014 (Actual)
Primary Completion Date
July 2019 (Actual)
Study Completion Date
August 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Th17 Helper Immune Cells, Autoimmunity, Salt Intake, Sodium Chloride

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subjects in study
Arm Type
Other
Arm Description
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)
Intervention Type
Dietary Supplement
Intervention Name(s)
Low salt diet
Intervention Description
Low salt diet, 10mmoL of sodium per day, for 6 days
Intervention Type
Dietary Supplement
Intervention Name(s)
Low salt diet + IV normal saline
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Liberal salt diet
Intervention Description
Liberal salt diet targeting 200 mmoL of sodium per day x 7 days
Primary Outcome Measure Information:
Title
TH-17 levels
Time Frame
5 days
Secondary Outcome Measure Information:
Title
IL-17 levels
Time Frame
5 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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: Complete blood count Serum creatinine, sodium, potassium, glucose, liver enzymes Urinalysis 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Williams, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Salt and TH-17 in Healthy Human Subjects

We'll reach out to this number within 24 hrs