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Salt and TH-17 in Healthy Human Subjects

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ClinicalTrials.gov Identifier: NCT02261688
Recruitment Status : Active, not recruiting
First Posted : October 10, 2014
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):
Gordon H. Williams, MD, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
Th17 Helper Immune Cells Autoimmunity Salt Intake Sodium Chloride Dietary Supplement: Low salt diet Dietary Supplement: Low salt diet + IV normal saline Dietary Supplement: Liberal salt diet Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Evaluation of the Influence of Salt Intake on TH17 Interleukin(IL)-17 Producing CD4+ Helper T Cells in Human Subjects
Actual Study Start Date : March 2014
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sodium

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. TH-17 levels [ Time Frame: 5 days ]

Secondary Outcome Measures :
  1. IL-17 levels [ Time Frame: 5 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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:

  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)

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): NCT02261688


Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Gordon Williams, MD Brigham and Women's Hospital

Responsible Party: Gordon H. Williams, MD, Chief, Cardiovascular Endocrinology Section, Brigham and Women's Hospital, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02261688     History of Changes
Other Study ID Numbers: 2013P002358
First Posted: October 10, 2014    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Autoimmune Diseases
Immune System Diseases