Effects Of Sodium Glucose Cotranspoter 2 Inhibitors On Heart And Kidneys In Fabry Disease Patients

Effects Of Sodium Glucose Cotranspoter 2 Inhibitors On Heart And Kidneys In Fabry Disease Patients; A Prospective, Randomized, Double-Blind, Placebo- Controlled Study.

The goal of this clinical trial is to test dapagliflizone in Fabry patients. The main questions it aims to answer are:

• Has 10 mg/d of dapagliflozin a positive effect on kidney functions of Fabry patients.
• Has 10 mg/d of dapagliflozin a positive effect on heart functions in Fabry patients.

Participants will be asked to

• Sign an informed consent
• Give a blood and urine samples
• Be subjected to Echocardiography investigation
• Take 10 mg/day Dapagliflizone

Researchers will compare treatment to placebo groups to see if kidneys and heart functions will be improved in the treatment group better more than the placebo group.

Study Overview

• Status: Not yet recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Albina Nowak, MD; Phone Number: +41 (0)43 253 8872; Email: albina.nowak@usz.ch
• Study Contact Backup: Name: Israa Abdullah, MD-PhD; Phone Number: +41762710188; Email: israa.abdullah@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age: 18-70 years
• Patients with genetically confirmed Fabry disease.
• On treatment with Enzyme Replacement Therapy (ERT).
• ERT or chaperone therapy at stable dose for at least 3 last months
• Albuminuria >35 mg/day and/or proteinuria >150 mg/day
• eGFR ≥25 mL/min/1.73 m2
• On a stable dose of an ACEi, ARB or renin receptors blockers for at least 4 weeks prior to randomization
• Sufficient command of German language.
• Signed and dated informed consent.
• Known cardiac association of FD

Exclusion Criteria:

• Known hypersensitivity, allergy or contraindications to dapagliflozin.
• Diagnosis of type 1 or type 2 diabetes mellitus
• Patients with any disease (other than Fabry disease) affecting the heart and the kidnys.
• History of kidney transplantation.
• Active malignancy.
• Use of the co-interventional treatments (Aldosterone antagonists, Continuous use of NSAIDs or systemic steroids) within 6 weeks of screening will not be allowed.

• Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:

  1. History of active inflammatory bowel disease within the last six months;
  2. Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  3. Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
  4. Pancreatic injury or pancreatitis within the last six months;
  5. Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
• Subject who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing.
• Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
• Women who are pregnant or breast feeding; intention to become pregnant during the course of the study, lack of safe contraception.
• Patients with known or suspected non-compliance, drug or alcohol abuse, including Marijuana cigarettes.
• Participation in another study with investigational drugs within the 30 days preceding and during the present study.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dapagliflozin 10mg Tab; SGLT2is- Dapagliflozin (Forxiga): 10 mg/d, oral drug	Drug: Dapagliflozin 10mg Tab; Forxiga® as an add-on treatment in patients with renal and/or cardiac association FD in an exploratory framework.
PLACEBO_COMPARATOR: Placebo; Placebo tablet will have the same color, taste, smell and package as the verum tablet	Drug: Placebo; matched oral drug. Placebo tablet will have the same color, taste, smell and package as the verum tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the change of eGFR in treatment months 6, 12 and at baseline	The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2009 formula are used to evaluate the calculated GFR. eGFR in month 6 and 12 are compared to baseline eGFR.	Baseline, 6 months and 12 months
Assess the change of Protein /creatinine ratio in urine	Total protein is measured in the morning sample of urine, minimal volume of 10 ml are collected and analyzed using Immune nephelometry method. Protein concentration are reported in relation to creatinine.	Baseline, 6 months and 12 months
Assess the change of Albumin/creatinine ratio in urine	Albumin is measured in the morning sample of urine, minimal volume of 10 ml are collected and analyzed using Immune nephelometry method. Albumin concentration are reported in relation to creatinine.	Baseline, 6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-pro BNP level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo	NT-pro BNP are assessed using a minimal of 2.5 ml heparin-plasma sample with Electro- Chemiluminescent Immunoassay technique.	Baseline, 6 months and 12 months
Troponin I levels will be assessed at baseline and after 6 and 12 months of treatment with	Troponin I are measured in heparin whole blood (min. 2.5 ml) using Chemiluminescent Microparticle Immunoassay.	Baseline, 6 months and 12 months
LVMMI parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo	LVMMI parameter are assessed using M-mode echocardiography in Cardiology clinic	Baseline, 6 months and 12 months
Septal thickness parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo	Septal thickness parameter are assessed using M-mode echocardiography in Cardiology clinic	Baseline, 6 months and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chlosterol level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo	Chlosterol level are measured using a minimal of 2.5 ml heparin-plasma sample with Enzymatic color test (CHOD-POD method)	Baseline, 6 months and 12 months

Collaborators and Investigators

• Sponsor: Albina Nowak, MD

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2023
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (ACTUAL): February 2, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2023
• Last Update Submitted That Met QC Criteria: January 23, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: SGLT2Is46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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