Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks
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|ClinicalTrials.gov Identifier: NCT03374215|
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : June 28, 2022
The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited.
To study the genes that may cause primary aldosteronism in Black individuals.
People ages 18-70 who:
Are Black, African American, or of Caribbean descent
And have difficult to control blood pressure or primary aldosteronism
Relatives of people with primary aldosteronism
Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests.
Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include:
Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent.
Urine tests: Some require a high-salt diet for 3 days.
Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein.
Small hair sample taken from near the scalp.
Bone density scan: Participants lie on a table while a camera passes over the body.
If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include:
- Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery.
- Taking drugs to block the effects of aldosterone
Participants may return about 1 year later to repeat testing.
|Condition or disease|
|Adrenal Gland Neoplasm Hypertension Bone Diseases, Metabolic Cardiovascular Disease Hyperinsulinemia|
Primary Aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 6-8% of hypertension and 14-25% of resistant hypertension. This prevalence translates to approximately 1 in 30-50 adults or about 4,000,000 Americans with PA. Until recently, the deleterious effects of PA were thought to derive solely from aldosterone-mediated sodium retention and associated blood pressure rise. However, animal studies and clinical trials demonstrate that mineralocorticoid receptor (MR) blockade has cardio- and reno-protective effects that clearly exceed those expected from blood pressure reduction alone. Growing evidence supports the concept that excess aldosterone, in the presence of elevated blood pressure, initiates a cascade characterized by fibrosis, oxidative stress, and activation of pro-inflammatory and pro-fibrotic pathways, leading to morbidity via worsened insulin sensitivity, impaired bone formation, and accelerated cardiovascular remodeling. Recent studies have identified several new genetic underpinnings of PA, both germline and somatic, including mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and ARMC5. As the effects of chronic hyperaldosteronism differ between races, it is not surprising that the relative prevalence of these mutations differs among cohorts. African Americans (AA) in particular have increased susceptibility to end-organ damage from aldosterone excess-induced cardiovascular remodeling. They are more likely to have congestive heart failure, end-stage renal disease, and atherosclerotic events than age-matched Caucasians. However, to date no comprehensive analysis of mutations in PA has been performed in AA. (Note: for the purposes of this protocol, the terms Black or African American incorporate individuals who self-identify as Black, African American, or the Caribbean diaspora).
The aims of this study are to identify the germline and/or somatic mutations causing PA in AA, define the effects of these mutations on aldosterone production in AA, and to identify effective pharmacologic agents that will inhibit inappropriate aldosterone production in target cells. Aldosterone producing adenoma (APA) and other adrenocortical tumor (ACT) specimens will be gathered from archival (collected under protocol 00-CH-160 and other related NIH studies) and prospective research subjects with PA that will be evaluated at the NIH Clinical Research Center under the proposed protocol. Samples will be analyzed using state-of-the-art next-generation sequencing (NGS). Human adrenal cell lines (H295R and others, as appropriate) will be used to study the mutations effect on aldosterone production. Additionally, this will help identify possible effective pharmacologic therapeutics to treat PA. Animal models of novel genetic causes of PA may also be created to study the molecular mechanisms underpinning the disease.
|Study Type :||Observational|
|Estimated Enrollment :||1150 participants|
|Official Title:||Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks|
|Actual Study Start Date :||December 14, 2017|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
Adult AA with primary aldosteronism
Adult individuals (age 18 or older) with HTN and discrete adrenal masses or bilateral hyperplasia of the adrenal glands, with outpatient positive ARR or string clinical suspicion for PA
Family members age >= 7 of participants
DNA from relatives of patients (age 7 or older)
- To define the germline and/or somatic genetic events causing Primary Aldosteronism (PA) in Blacks. [ Time Frame: baseline, end of study ]define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.
- To define the effects of mutations in Black subjects on adrenocortical tumor formation, function and aldosterone production. [ Time Frame: Continuous ]define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.
- To investigate the clinical utility of other biomarkers in the subtype classification of PA. [ Time Frame: baseline, end of study ]define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.
- To investigate the cardiovascular, renal, metabolic, bone, and coagulopathic consequences of PA in AA, as well as any changes after one year of directed therapeutic intervention (e.g. post-adrenalectomy or mineralocorticoid receptor antagonist t... [ Time Frame: baseline, end of study ]
- To investigate co-secretion of other steroids in PA. [ Time Frame: baseline, end of study ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374215
|Contact: Lola E Saidkhodjaeva, R.N.||(301) firstname.lastname@example.org|
|Contact: Crystal Dawn C Kamilaris, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Crystal Dawn C Kamilaris, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|