Salt-Sensitivity Blood Pressure Study in Healthy Subjects

Overseen By Jonathan S Williams, MD, MMSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must not be taking: NSAIDs, Steroids, Decongestants, others

Disqualifiers: Pregnancy, Breastfeeding, Alcohol, Tobacco, others

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how dietary salt affects blood pressure by examining a specific enzyme called Lysine-specific demethylase 1. Participants will receive a treatment targeting this enzyme (Lysine-specific demethylase 1 inhibitor) to determine its effectiveness in managing blood pressure in salt-sensitive individuals. The trial includes different groups based on genetic factors and racial backgrounds, focusing on Caucasians and African Americans with certain genes. Ideal candidates are healthy individuals without a history of high blood pressure or other major health issues, who are not on medications or using tobacco. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on blood pressure management.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking any medications or herbal preparations to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a protein called Lysine-specific demethylase 1 (LSD1) plays a role in how the body manages salt, influencing blood pressure. In animal studies, those lacking LSD1 experienced more significant blood pressure changes on a high-salt diet compared to normal animals, meaning their blood pressure increased more with high salt intake.

Regarding human safety, these studies do not provide direct information about the safety of LSD1 inhibitors. The research focuses on understanding how changes in the LSD1 gene affect blood pressure. The trial is in an early stage, labeled "Not Applicable," primarily exploring the treatment's effects rather than offering a complete safety profile. This indicates that safety information is still being collected.

Prospective participants should discuss any known risks or side effects with the study team. They can provide the most up-to-date and specific information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for salt-sensitive blood pressure focus on lifestyle changes or medications like diuretics and ACE inhibitors that help manage blood volume or hormone levels. However, the Lysine-specific demethylase 1 (LSD1) inhibitor is different because it targets a genetic factor linked to salt sensitivity. Researchers are excited about this treatment because it offers a new mechanism of action by inhibiting LSD1, potentially providing a more personalized and effective approach for individuals with specific genetic backgrounds. This could lead to more precise blood pressure control for those who don't respond well to standard treatments.

What evidence suggests that this trial's treatments could be effective for regulating blood pressure?

Research has shown that a protein called LSD1 affects how salt influences blood pressure. Studies have found that people with certain types of the LSD1 gene and mice with changes in LSD1 tend to have higher blood pressure when they consume more salt. This indicates that LSD1 plays a crucial role in how the body manages salt and blood pressure. In this trial, researchers are examining the effects of an LSD1 inhibitor on blood pressure across different genetic groups. By blocking LSD1, the treatment might lessen salt's impact on blood pressure, potentially aiding those sensitive to salt. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for healthy Caucasian or African American individuals aged 25-45, with normal blood pressure and no history of major diseases like hypertension, diabetes, or heart disease. Participants must not be overweight (BMI <25), drink more than 6oz alcohol weekly, use tobacco/drugs/NSAIDs, be pregnant/breastfeeding, have certain drug sensitivities or recent steroid use.

Inclusion Criteria

Age 25-45 years

Caucasian or African American

No gender preference (anticipate 50% female)

Exclusion Criteria

You drink more than 6 ounces of alcohol per week.

You have used illegal drugs.

You have been regularly using NSAIDs (like ibuprofen or naproxen) for a long time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Low Salt Diet

Participants consume a low salt diet for one week

1 week

1 visit (in-person, overnight stay)

High Salt Diet

Participants consume a high salt diet for one week

1 week

1 visit (in-person, overnight stay)

Follow-up

Participants are monitored for hormonal and vascular responses after dietary interventions

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Lysine-specific demethylase 1 inhibitor

Trial Overview

The study aims to understand how dietary salt affects blood pressure regulation through the enzyme Lysine-specific demethylase 1. It will measure changes in vascular stiffness, kidney blood flow response to salt intake and aldosterone levels after Angiotensin II infusion.

How Is the Trial Designed?

Group I: Afr-Amer risk allele Active Control 3 Interventions

African Americans carrying the LSD1 affected allele

Group II: Cauc risk allele Placebo Group 3 Interventions

Caucasians carrying the LSD1 affected allele

Group III: Cauc non-risk allele Placebo Group 3 Interventions

Caucasians carrying the LSD1 non-risk allele

Group IV: Afr-Amer non-risk allele Placebo Group 3 Interventions

African Americans carrying the LSD1 non-risk allele

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3776098/

Lysine-specific demethylase-1 modifies the age effect on ...

Our results demonstrate significantly increased blood pressure salt sensitivity in LSD1-deficient compared to wild-type animals with age, confirming our ...

2.

ahajournals.org

ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.13821

Lysine-Specific Demethylase-1 Deficiency Increases ...

Here, we show that LSD1 genotype (in humans) and LSD1 deficiency (in mice) lead to similar associations with increased blood pressure and urine ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9016472/

Salt Sensitivity of Blood Pressure and Aldosterone: Interaction ...

Lysine-specific demethylase 1 (LSD1) is a salt-sensitive epigenetic regulator associated with SSBP and aldosterone dysfunction. An LSD1 risk allele in humans is ...

4.

mdpi.com

mdpi.com/1420-3049/29/2/550

Lysine-Specific Demethylase 1 Inhibitors

This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010.

5.

journals.physiology.org

journals.physiology.org/doi/10.1152/ajpheart.00513.2011

Histone demethylase LSD1 deficiency during high-salt diet ...

Thus, during the HS diet, LSD1 deficiency is associated with hypertension, enhanced vascular contraction, and reduced relaxation via NO-cGMP pathway. The data ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0085253823004933

Novel mechanisms of salt-sensitive hypertension

Lysine-specific histone demethylase-1 (LSD1) deficiency modifies the age effect on blood pressure salt sensitivity and develops salt-sensitive hypertension ...