Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

NCT03029806 | Active Not Recruiting

• 1 other identifier: 2015P002540
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• Aldosterone response to angiotensin II

  Change in aldosterone, baseline to after angiotensin II by genotype/race

  After 1 week dietary salt manipulation

Secondary Outcomes (2)

• Renal blood flow response to dietary salt

  After 1 week dietary salt manipulation on both diets

• Vascular stiffness response to angiotensin II

  After 1 week dietary salt manipulation

Study Arms (4)

Afr-Amer risk allele

ACTIVE COMPARATOR

African Americans carrying the LSD1 affected allele

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

Cauc risk allele

PLACEBO COMPARATOR

Caucasians carrying the LSD1 affected allele

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

Afr-Amer non-risk allele

PLACEBO COMPARATOR

African Americans carrying the LSD1 non-risk allele

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

Cauc non-risk allele

PLACEBO COMPARATOR

Caucasians carrying the LSD1 non-risk allele

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

Interventions

Aldosterone response to AngII LS OTHER

Change in aldosterone from baseline to after Ang II infusion on a LS diet

Afr-Amer non-risk allele; Afr-Amer risk allele; Cauc non-risk allele; Cauc risk allele

Renal blood flow response to salt OTHER

Change in renal blood flow: High salt to low salt diet

Afr-Amer non-risk allele; Afr-Amer risk allele; Cauc non-risk allele; Cauc risk allele

Vascular Stiffness OTHER

Change in vascular stiffness, baseline compared to AngII

Afr-Amer non-risk allele; Afr-Amer risk allele; Cauc non-risk allele; Cauc risk allele

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (4)

• 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.

  PMID: 23054827 BACKGROUND

• 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.

  PMID: 22534796 BACKGROUND

• 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.

  PMID: 21873498 BACKGROUND

• Heydarpour M, Parksook WW, Pojoga LH, Williams GH, Williams JS. Mineralocorticoid Receptor and Aldosterone: Interaction Between NR3C2 Genetic Variants, Sex, and Age in a Mixed Cohort. J Clin Endocrinol Metab. 2024 Dec 18;110(1):e140-e149. doi: 10.1210/clinem/dgae127.

  PMID: 38437868 DERIVED

MeSH Terms

Interventions

Vascular Stiffness

Intervention Hierarchy (Ancestors)

Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician, Brigham and Women's Hospital

Model Details: Heathy volunteers

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: January 2, 2017
• Primary Completion: January 2, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)