Natriuretic Effect of Amiloride in Relation to the Alpha Adducin Gene (ADD-AMI) RS4961 Variant

San Donato Group (GSD)

Status and phase: Completed; Phase 3

Conditions: Salt Excess; Genetic Hypertension; Hypertension Essential

Treatments: Drug: Amiloride

Study type: Interventional

Funder types: Other

Identifiers

NCT06416735

ADD-AMI

Details and patient eligibility

About

The study is a non-pharmacological interventional, single-center, national, non-randomised, comparative and open label.

Full description

The study is carried out to evaluate primarily the difference in the activity of the renal transporter ENaC (through dosage of sodium) through its inhibition with a single dose of Amiloride in hypertensive patients characterized by the polymorphism of alpha Adducin rs496. It's also aimed to see the difference in potassium and the change in systolic and diastolic blood pressure after amiloride administration

Enrollment: 40 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• male patients aged 18-60 years;
• naïve hypertensive patients: newly diagnosed, never previously treated for hypertension;
• BMI<30 Kg/m2,
• documented first degree essential arterial hypertension (mean of the last 3 consecutive systolic BP measurements must be >=140 mmHg or diastolic BP >=90 mmHg;
• signature of the informed consent for participation in the study
• patient who has already undergone genomic DNA sampling (accompanied by relative consent) and genotyped for the ADD1 rs4961 variant (GG, GT or TT).

Exclusion criteria

known causes of secondary hypertension;

• severe or malignant hypertension; history of renal artery disease;
• significant renal disease (creatinine clearance less than 60 ml/min);
• hyperkalemia (Kpl > 6mEq/l) at enrollment visit;
• hypercalcaemia (Ca pl > 2.6 mmol/l) at enrollment visit;
• symptomatic hyperuricemia (> 7.5 mg/dl);
• liver disease (transaminases greater than 3 times the normal value);
• cardiac pathologies (myocardial infarction, atrial fibrillation, etc.);
• diabetes (fasting blood sugar >125mg/dl);
• in therapy with statins, NSAIDs, systemic steroids;
• known hypersensitivity to Amiloride or to any of the excipients;
• patients unable to express a valid consent -

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

patients carrying the wild-type (GG) genotype of ADD1 rs4961

Experimental group

Description:

The protocol involves a test of oral administration of a single dose of Amiloride (5 or 10 mg based on body weight) to 20 patients carrying the wild-type (GG) genotype of ADD1 rs4961

Treatment:

Drug: Amiloride

patients carriers of variant T (GT or TT)

Experimental group

Description:

The test involves the administration of a single dose of 5 or 10 mg of Amiloride to 20 hypertensive carriers of the T variant (GT or TT)

Treatment:

Drug: Amiloride