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

Phase 3

Completed

• Conditions: Hypertension Essential; Salt Excess; Genetic Hypertension
• Interventions: Drug: Amiloride

• Registration Number: NCT06416735
• Lead Sponsor: Ospedale San Raffaele

Brief Summary

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

Detailed 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

Study Timeline

• Study Start: 2018-09-28
• Primary Completion: 2020-07-20
• Study Completion: 2020-07-20
• Study First Submitted: 2023-09-04
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-11
• Last Update Submitted: 2024-05-11
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 40

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 -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
patients carriers of variant T (GT or TT)	Amiloride	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)
patients carrying the wild-type (GG) genotype of ADD1 rs4961	Amiloride	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

Primary Outcome Measures

Name	Time	Method
Evaluate urinary sodium	3 hrs and 6 hrs	Evaluation of sodium levels after oral administration of Amiloride

Secondary Outcome Measures

Name	Time	Method
Evaluate potassium levels	3 hrs and 6 hrs	Evaluation of potassium plasma levels after oral administration of Amiloride
Evaluation of systolic blood pressure	3 hrs and 6 hrs	Evaluation of systolic blood pressure after oral administration of Amiloride
Evaluation of diastolic blood pressure	3 hrs and 6 hrs	Evaluation of diastolic blood pressure after oral administration of Amiloride

Trial Locations

Locations (1)

San Raffaele Hospital; 🇮🇹 Milan, Lombardia, Italy