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

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

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

Study Overview

• Status: Completed
• Conditions: Genetic Hypertension; Hypertension Essential; Salt Excess
• Intervention / Treatment: Drug: Amiloride

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Lombardia
    • Milan, Lombardia, Italy, 20132
      • San Raffaele Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients carrying the wild-type (GG) genotype of ADD1 rs4961; 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	Drug: Amiloride; administration of a single dose of 5 or 10 mg of Amiloride (based on body weight) After oral intake of the drug, the increase in sodium in the urine ends within 8 hours
Experimental: patients carriers of variant T (GT or TT); 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)	Drug: Amiloride; administration of a single dose of 5 or 10 mg of Amiloride (based on body weight) After oral intake of the drug, the increase in sodium in the urine ends within 8 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate urinary sodium	Evaluation of sodium levels after oral administration of Amiloride	3 hrs and 6 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate potassium levels	Evaluation of potassium plasma levels after oral administration of Amiloride	3 hrs and 6 hrs
Evaluation of systolic blood pressure	Evaluation of systolic blood pressure after oral administration of Amiloride	3 hrs and 6 hrs
Evaluation of diastolic blood pressure	Evaluation of diastolic blood pressure after oral administration of Amiloride	3 hrs and 6 hrs

Collaborators and Investigators

• Sponsor: Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Actual): July 20, 2020
• Study Completion (Actual): July 20, 2020

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: May 11, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 11, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Hypertension; Salt
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Amiloride
• Other Study ID Numbers: ADD-AMI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No