Clinical trial NCT05710367: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Fabry Disease
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2023-02-02
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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.

Primary outcomes:
measure: Assess the change of eGFR in treatment months 6, 12 and at baseline
timeFrame: Baseline, 6 months and 12 months
measure: Assess the change of Protein /creatinine ratio in urine
timeFrame: Baseline, 6 months and 12 months
measure: Assess the change of Albumin/creatinine ratio in urine
timeFrame: Baseline, 6 months and 12 months
Secondary outcomes:
measure: NT-pro BNP level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
timeFrame: Baseline, 6 months and 12 months
measure: Troponin I levels will be assessed at baseline and after 6 and 12 months of treatment with
timeFrame: Baseline, 6 months and 12 months
measure: LVMMI parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
timeFrame: Baseline, 6 months and 12 months
measure: Septal thickness parameter will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
timeFrame: Baseline, 6 months and 12 months
Other outcomes:
measure: Chlosterol level will be assessed at baseline and after 6 and 12 months of treatment with study drug and placebo
timeFrame: Baseline, 6 months and 12 months
Locations:
Study officials:
References: