Lysine-specific Demethylase 1 and Salt-sensitivity in Humans
- Conditions
- Healthy Subjects
- Interventions
- Other: Aldosterone response to AngII LSOther: Renal blood flow response to saltOther: Vascular Stiffness
- Registration Number
- NCT03029806
- Lead Sponsor
- Brigham and Women's Hospital
- Brief Summary
The purpose of this study is to investigate the role dietary salt plays in epigenetic regulation of blood pressure, focusing on the salt-sensitive regulatory enzyme Lysine-specific demethylase 1.
- Detailed Description
The purpose of this study is to investigate the role dietary salt plays in epigenetic regulation of blood pressure in African American and Caucasians, focusing on the salt-sensitive regulatory enzyme Lysine-specific demethylase 1. This might help us understand why some people develop high blood pressure.
Healthy volunteers will be screened for eligibility and invited to participate in a 2 weeks study. Week 1 will be consumption of a low salt diet. Week 2 will be a high salt diet.
At the end of each week, participants will be admitted to a Clinical Research Center overnight and for one day.
On the CRC, participants will remain fasting and supine overnight and then next morning undergo hormonal and vascular testing. This will consist of blood drawing, echocardiogram, vascular tonometry, and assessment of renal blood flow before and after a low-dose Angiotensin II infusion.
The study outcome will compare how variants in the LSD1 gene affect hormonal and vascular responses according to race. This information will help us determine why some races and genetic profiles are more susceptible to detrimental effects of salt in the diet while others are protected against these effects.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 88
- Age 25-45 years
- Caucasian or African American
- No gender preference (anticipate 50% female)
- Normotensive (screening blood pressure <140/90 mmHg)
- No history of hypertension, diabetes, stroke, coronary artery disease, kidney disease, cancer, thyroid disease, preeclampsia, or hospitalizations in 6 months
- Normal screening laboratory values (CMP, TSH, A1c)
- Normal ECG
- BMI <25 kg/m2
- Pregnancy
- Breast feeding
- Any medication or herbal preparation
- >6oz alcohol/week
- Tobacco use
- Illicit drug use
- Chronic NSAID use
- Recent steroid use (injected, inhaled, oral)
- Decongestant use in the past 2 weeks
- Known sensitivity to infused Angiotensin II or para-amino hippurate
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Afr-Amer risk allele Renal blood flow response to salt African Americans carrying the LSD1 affected allele Afr-Amer risk allele Vascular Stiffness African Americans carrying the LSD1 affected allele Afr-Amer risk allele Aldosterone response to AngII LS African Americans carrying the LSD1 affected allele Afr-Amer non-risk allele Aldosterone response to AngII LS African Americans carrying the LSD1 non-risk allele Cauc risk allele Renal blood flow response to salt Caucasians carrying the LSD1 affected allele Cauc risk allele Vascular Stiffness Caucasians carrying the LSD1 affected allele Cauc non-risk allele Renal blood flow response to salt Caucasians carrying the LSD1 non-risk allele Cauc risk allele Aldosterone response to AngII LS Caucasians carrying the LSD1 affected allele Afr-Amer non-risk allele Renal blood flow response to salt African Americans carrying the LSD1 non-risk allele Afr-Amer non-risk allele Vascular Stiffness African Americans carrying the LSD1 non-risk allele Cauc non-risk allele Aldosterone response to AngII LS Caucasians carrying the LSD1 non-risk allele Cauc non-risk allele Vascular Stiffness Caucasians carrying the LSD1 non-risk allele
- Primary Outcome Measures
Name Time Method Aldosterone response to angiotensin II After 1 week dietary salt manipulation Change in aldosterone, baseline to after angiotensin II by genotype/race
- Secondary Outcome Measures
Name Time Method Vascular stiffness response to angiotensin II After 1 week dietary salt manipulation Change in vascular stiffness, baseline to after angiotensin II by genotype/race
Renal blood flow response to dietary salt After 1 week dietary salt manipulation on both diets Change in renal blood flow, high salt diet to low salt diet by genotype/race
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States