Clinical Trial Details
— Status: Suspended
Administrative data
NCT number |
NCT03374215 |
Other study ID # |
180031 |
Secondary ID |
18-CH-0031 |
Status |
Suspended |
Phase |
|
First received |
|
Last updated |
|
Start date |
December 14, 2017 |
Est. completion date |
December 31, 2025 |
Study information
Verified date |
February 13, 2024 |
Source |
National Institutes of Health Clinical Center (CC) |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Background:
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.
Objective:
To study the genes that may cause primary aldosteronism in Black individuals.
Eligibility:
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
Design:
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:
Medical history
Physical exam
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.
Heart tests
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.
Kidney ultrasound
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:
1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients
will have follow-up visits 2-4 weeks after surgery.
2. Taking drugs to block the effects of aldosterone
Participants may return about 1 year later to repeat testing.
Description:
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.