Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

Healthy Subjects Clinical Trial

Official title:

Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03029806
• Other study ID #: 2015P002540
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 2, 2017
• Est. completion date: January 2, 2024

Study information

• Verified date: February 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: January 2, 2024
• Est. primary completion date: January 2, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Subjects
• Hypersensitivity

Intervention

Other:
• Aldosterone response to AngII LS
Change in aldosterone from baseline to after Ang II infusion on a LS diet
• Renal blood flow response to salt
Change in renal blood flow: High salt to low salt diet
• Vascular Stiffness
Change in vascular stiffness, baseline compared to AngII

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

Krug AW, Tille E, Sun B, Pojoga L, Williams J, Chamarthi B, Lichtman AH, Hopkins PN, Adler GK, Williams GH. Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake. Age (Dordr). 2013 Oct;35(5):1809-20. doi: 10.1007/s11357-012-9480-0. Epub 2012 Oct 2. — View Citation

Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR, Reslan OM, Adler GK, Williams GH, Shi Y, Khalil RA. Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1862-71. doi: 10.1152/ajpheart.00513.2011. Epub 2011 Aug 26. — View Citation

Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Ida Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension. Am J Hypertens. 2012 Jul;25(7):812-7. doi: 10.1038/ajh.2012.43. Epub 2012 Apr 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aldosterone response to angiotensin II	Change in aldosterone, baseline to after angiotensin II by genotype/race	After 1 week dietary salt manipulation
Secondary	Renal blood flow response to dietary salt	Change in renal blood flow, high salt diet to low salt diet by genotype/race	After 1 week dietary salt manipulation on both diets
Secondary	Vascular stiffness response to angiotensin II	Change in vascular stiffness, baseline to after angiotensin II by genotype/race	After 1 week dietary salt manipulation