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

Primary Purpose

Fabry Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Dapagliflozin 10mg Tab
Placebo
Sponsored by
Albina Nowak, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fabry Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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. 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Dapagliflozin 10mg Tab

    Placebo

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.

    Secondary Outcome Measures

    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.
    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.
    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
    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

    Full Information

    First Posted
    January 10, 2023
    Last Updated
    January 23, 2023
    Sponsor
    Albina Nowak, MD
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05710367
    Brief Title
    Effects Of Sodium Glucose Cotranspoter 2 Inhibitors On Heart And Kidneys In Fabry Disease Patients
    Official Title
    Effects Of Sodium Glucose Cotranspoter 2 Inhibitors On Heart And Kidneys In Fabry Disease Patients; A Prospective, Randomized, Double-Blind, Placebo- Controlled Study.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2023 (Anticipated)
    Primary Completion Date
    August 2024 (Anticipated)
    Study Completion Date
    August 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Albina Nowak, MD

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Fabry Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    46 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Dapagliflozin 10mg Tab
    Arm Type
    Experimental
    Arm Description
    SGLT2is- Dapagliflozin (Forxiga): 10 mg/d, oral drug
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo tablet will have the same color, taste, smell and package as the verum tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Dapagliflozin 10mg Tab
    Intervention Description
    Forxiga® as an add-on treatment in patients with renal and/or cardiac association FD in an exploratory framework.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    matched oral drug. Placebo tablet will have the same color, taste, smell and package as the verum tablet
    Primary Outcome Measure Information:
    Title
    Assess the change of eGFR in treatment months 6, 12 and at baseline
    Description
    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.
    Time Frame
    Baseline, 6 months and 12 months
    Title
    Assess the change of Protein /creatinine ratio in urine
    Description
    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.
    Time Frame
    Baseline, 6 months and 12 months
    Title
    Assess the change of Albumin/creatinine ratio in urine
    Description
    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.
    Time Frame
    Baseline, 6 months and 12 months
    Secondary Outcome Measure Information:
    Title
    NT-pro BNP level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
    Description
    NT-pro BNP are assessed using a minimal of 2.5 ml heparin-plasma sample with Electro- Chemiluminescent Immunoassay technique.
    Time Frame
    Baseline, 6 months and 12 months
    Title
    Troponin I levels will be assessed at baseline and after 6 and 12 months of treatment with
    Description
    Troponin I are measured in heparin whole blood (min. 2.5 ml) using Chemiluminescent Microparticle Immunoassay.
    Time Frame
    Baseline, 6 months and 12 months
    Title
    LVMMI parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
    Description
    LVMMI parameter are assessed using M-mode echocardiography in Cardiology clinic
    Time Frame
    Baseline, 6 months and 12 months
    Title
    Septal thickness parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
    Description
    Septal thickness parameter are assessed using M-mode echocardiography in Cardiology clinic
    Time Frame
    Baseline, 6 months and 12 months
    Other Pre-specified Outcome Measures:
    Title
    Chlosterol level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
    Description
    Chlosterol level are measured using a minimal of 2.5 ml heparin-plasma sample with Enzymatic color test (CHOD-POD method)
    Time Frame
    Baseline, 6 months and 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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: 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. 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Albina Nowak, MD
    Phone
    +41 (0)43 253 8872
    Email
    albina.nowak@usz.ch
    First Name & Middle Initial & Last Name or Official Title & Degree
    Israa Abdullah, MD-PhD
    Phone
    +41762710188
    Email
    israa.abdullah@usz.ch

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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

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