Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

Mass General Brigham

Status: Active, not recruiting

Conditions: Healthy Subjects

Treatments: Other: Aldosterone response to AngII LS; Other: Vascular Stiffness; Other: Renal blood flow response to salt

Study type: Interventional

Funder types: Other

Identifiers

NCT03029806

2015P002540

Details and patient eligibility

About

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.

Full 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.

Enrollment: 88 estimated patients

Sex: All

Ages: 25 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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88 participants in 4 patient groups, including a placebo group

Afr-Amer risk allele

Active Comparator group

Description:

African Americans carrying the LSD1 affected allele

Treatment:

Other: Renal blood flow response to salt

Other: Vascular Stiffness

Other: Aldosterone response to AngII LS

Cauc risk allele

Placebo Comparator group

Description:

Caucasians carrying the LSD1 affected allele

Treatment:

Other: Renal blood flow response to salt

Other: Vascular Stiffness

Other: Aldosterone response to AngII LS

Afr-Amer non-risk allele

Placebo Comparator group

Description:

African Americans carrying the LSD1 non-risk allele

Treatment:

Other: Renal blood flow response to salt

Other: Vascular Stiffness

Other: Aldosterone response to AngII LS

Cauc non-risk allele

Placebo Comparator group

Description:

Caucasians carrying the LSD1 non-risk allele

Treatment:

Other: Renal blood flow response to salt

Other: Vascular Stiffness

Other: Aldosterone response to AngII LS