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

NCT05710367 | Unknown Phase 2

• 1 other identifier: SGLT2Is46
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• NT-pro BNP level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo

  Baseline, 6 months and 12 months

• Troponin I levels will be assessed at baseline and after 6 and 12 months of treatment with

  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

  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

  Baseline, 6 months and 12 months

Other Outcomes (1)

• Chlosterol level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo

  Baseline, 6 months and 12 months

Study Arms (2)

Dapagliflozin 10mg Tab

EXPERIMENTAL

SGLT2is- Dapagliflozin (Forxiga): 10 mg/d, oral drug

Drug: Dapagliflozin 10mg Tab

Placebo

PLACEBO COMPARATOR

Placebo tablet will have the same color, taste, smell and package as the verum tablet

Drug: Placebo

Interventions

Dapagliflozin 10mg Tab DRUG

Forxiga® as an add-on treatment in patients with renal and/or cardiac association FD in an exploratory framework.

Dapagliflozin 10mg Tab

Placebo DRUG

matched oral drug. Placebo tablet will have the same color, taste, smell and package as the verum tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• History of active inflammatory bowel disease within the last six months;
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
• Pancreatic injury or pancreatitis within the last six months;
• 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.

Sponsors & Collaborators

• Albina Nowak, MD: lead

MeSH Terms

Conditions

Fabry Disease

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Albina Nowak, MD

CONTACT

+41 (0)43 253 8872; albina.nowak@usz.ch

Israa Abdullah, MD-PhD

CONTACT

+41762710188; israa.abdullah@usz.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Senior Physician of Endocrinology, Diabetes and Clinical Nutrition

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: February 2, 2023
• Study Start: August 1, 2023
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: February 2, 2023

Record last verified: 2023-01