Th17 Helper Immune CellsNCT02261688
Salt and TH-17 in Healthy Human Subjects
A study testing Low salt diet, Low salt diet + IV normal saline and Liberal salt diet in people with Th17 Helper Immune Cells and Autoimmunity, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Th17 Helper Immune Cells, Autoimmunity, Salt Intake
- What is being tested?
- Low salt diet, Low salt diet + IV normal saline and Liberal salt diet
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 23Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: 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.
Read the 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.
- Conditions
- Th17 Helper Immune Cells, Autoimmunity, Salt Intake, Sodium Chloride
- Being tested
- Low salt diet, Low salt diet + IV normal saline, Liberal salt diet
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low salt dietDietary supplement
Low salt diet, 10mmoL of sodium per day, for 6 days
Low salt diet + IV normal salineDietary supplement
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.
Liberal salt dietDietary supplement
Liberal salt diet targeting 200 mmoL of sodium per day x 7 days
| Study group | Role | What they receive |
|---|---|---|
| Subjects in study | Other | 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) Receives: Dietary Supplement: Low salt diet; Dietary Supplement: Low salt diet + IV normal saline; Dietary Supplement: Liberal salt diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
TH-17 levels
Measured: 5 days
Secondary outcomes (1)
IL-17 levels
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2014 (estimated)
- Study startMar 2014
- Primary completionJul 2019
- Study completionAug 2019
Why it stopped: Lack of funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Th17 Helper Immune CellsStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gordon H. Williams, MD, Brigham and Women's Hospital
- Investigators
- Gordon Williams, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02261688
- Sponsor's protocol ID
- 2013P002358
- Status last verified
- Jun 2021
- First submitted
- 7 Oct 2014
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Influence of Salt Intake on TH17 Interleukin(IL)-17 Producing CD4+ Helper T Cells in Human Subjects
- ClinicalTrials.gov ID
- NCT02261688
- Acronym / sponsor ID
- 2013P002358
- Conditions
- Th17 Helper Immune Cells, Autoimmunity, Salt Intake, Sodium Chloride
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funds
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Mar 2014 (actual)
- Primary completion
- Jul 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 10 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects in study | Other | Dietary Supplement: Low salt diet, Dietary Supplement: Low salt diet + IV normal saline, Dietary Supplement: Liberal salt dietAll 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) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
- Complete blood count
- Serum creatinine, sodium, potassium, glucose, liver enzymes
- Urinalysis
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low salt dietLow salt diet, 10mmoL of sodium per day, for 6 days | Dietary supplement | Subjects in study |
| Low salt diet + IV normal salineLow 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 | Subjects in study |
| Liberal salt dietLiberal salt diet targeting 200 mmoL of sodium per day x 7 days | Dietary supplement | Subjects in study |
Primary outcome
TH-17 levels
Time frame: 5 days
1 secondary outcome
IL-17 levels
Time frame: 5 days
Results and safety
The study was stopped early (reason given: Lack of funds). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordon Williams, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low salt diet, Low salt diet + IV normal saline and Liberal salt diet in people with Th17 Helper Immune Cells and Autoimmunity, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of funds). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TH-17 levels (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.