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Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects (TRANSLATE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by University Health Network, Toronto
Sponsor:
Collaborators:
AstraZeneca
University of Toronto
Toronto General Hospital
Information provided by (Responsible Party):
David Z.I. Cherney, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT02585804
First received: October 22, 2015
Last updated: NA
Last verified: October 2015
History: No changes posted
  Purpose
Patients with Focal Segmental Glomerulosclerosis (FSGS) constitute an increasing proportion of the total glomerulonephritis (GN) patient cohort in North America while FSGS is a risk factor for end stage renal failure. Current non-immunological FSGS therapies include the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB), to reduce intraglomerular hypertension. Unfortunately, these agents lead to incomplete renal protection. The aim of the current study is to determine whether the addition of novel sodium glucose cotransport-2 inhibitors (SGLT2i) to standard of care leads to reduced intraglomerular pressure and suppression of proteinuria. We hypothesize that combination therapy of SGLT2i drugs and conventional RAASi results in additive renal protective effects in FSGS patients. A further goal is to examine mechanisms of SGLT2 inhibition by measuring renal hemodynamic function and sodium handling. Kidney function will be assessed in FSGS patients before and after an 8 week treatment with SGLT2i dapagliflozin.

Condition Intervention Phase
Focal Segmental Glomerulosclerosis
Drug: Dapagliflozin
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects: "The TRANSLATE Study"

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • The change in Glomerular Filtration Rate (GFR) After an 8 week treatment with dapagliflozin [ Time Frame: Before and after an 8 week treatment with dapagliflozin ] [ Designated as safety issue: No ]
    Glomerular Filtration Rate (GFR, based on plasma inulin clearance) will be measured at baseline and after 8 weeks of treatment.


Secondary Outcome Measures:
  • The change in Effective Renal Plasma Flow (ERPF) After an 8 week treatment with dapagliflozin [ Time Frame: Before and after an 8 week treatment with dapagliflozin ] [ Designated as safety issue: No ]
    Effective Renal Plasma Flow (ERPF, based on paraaminohippurate plasma clearance) will be measured at baseline and after 8 weeks of treatment.

  • The change in Blood Pressure After an 8 week treatment with dapagliflozin [ Time Frame: Before and after 8 weeks of treatment with dapagliflozin ] [ Designated as safety issue: No ]
  • The change in albuminuria after 8 weeks of treatment with dapagliflozin [ Time Frame: Before and after 8 weeks of treatment with dapagliflozin ] [ Designated as safety issue: No ]
  • The change in urinary vasoactive mediators after 8 weeks of treatment with dapagliflozin [ Time Frame: Before and after 8 weeks of treatment with dapagliflozin ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: September 2015
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dapagliflozin (trade name Farxiga®)
Oral tablet, 10mg, PO, 8 weeks
Drug: Dapagliflozin
Oral tablet, 10mg, PO, 8 weeks
Other Name: Trade name Farxiga®

Detailed Description:
FSGS and diabetic nephropathy may have common pathogenic mechanisms, that are mediated by intraglomerular hypertension, leading to hyperfiltration and proteinuria. Given that SGLT2i corrects early hemodynamic abnormalities in patients with diabetes, our aim is to determine if a similar benefit may extend to patients with FSGS. Based on previous experimental and clinical data, we hypothesize that SGLT2i will improve renal hemodynamic abnormalities characteristic of FSGS that promote renal injury and proteinuria.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects diagnosed with FSGS ≥1 month prior to informed consent
  • eGFR≥45 ml/min/1.73m2
  • Age 18 years or greater
  • No history of diabetes
  • Body Mass Index (BMI) 18.5 - 45.0 kg/ m2
  • Blood pressure ≥ 100/60 at screening
  • Stable therapy with either an ACEi or angiotensin II receptor blocker or direct renin inhibitor for > 1 month
  • > 1 g/day and <5 g/day of proteinuria unless the patient is not a candidate for immunosuppressive therapy

Exclusion Criteria:

  • Leukocyte and/or nitrite positive urinalysis that is untreated;
  • History of organ transplantation, cancer, liver disease;
  • Bariatric surgery or other gastrointestinal surgeries that induce chronic malabsorption within the past two years;
  • Current treatment with systemic corticosteroids, calcineurin inhibitors, or other immunosuppressant medications;
  • Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells;
  • Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practising an acceptable method of birth control;
  • Participation in another therapeutic trial with an investigational drug within 30 days prior to informed consent;
  • Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement;
  • Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase >3 x upper limit of normal as determined during screening;
  • Cardiac, lung or peripheral vascular disease or stroke;
  • Pancreas, pancreatic islet cells or renal transplant recipient;
  • Medical history of cancer or treatment for cancer in the last five years prior to screening;
  • History of allergy or angioedema with RAAS inhibitor exposure;
  • Kidney disease due primarily to another condition aside from FSGS;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02585804

Contacts
Contact: Vesta Lai, RN 416-340-4800 ext 8508 vesta.lai@uhn.ca
Contact: Harindra Rajasekeran, HBSc harindra.rajasekeran@utoronto.ca

Locations
Canada, Ontario
Renal Physiology Laboratory, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Vesta Lai, RN    416-340-4800 ext 8508    vesta.lai@uhn.ca   
Principal Investigator: David Z.I. Cherney, MD, PhD         
Sub-Investigator: Heather Reich, MD, PhD         
Sub-Investigator: Daniel C. Cattran, MD         
Sub-Investigator: Michelle Hladunewich, MD, MSc         
Sponsors and Collaborators
University Health Network, Toronto
AstraZeneca
University of Toronto
Toronto General Hospital
  More Information

Responsible Party: David Z.I. Cherney, Associate Professor of Medicine, Clinician Scientist, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02585804     History of Changes
Other Study ID Numbers: REB# 14-8284-B 
Study First Received: October 22, 2015
Last Updated: October 22, 2015
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
FSGS, SGLT2, chronic kidney disease, GFR, proteinuria

Additional relevant MeSH terms:
Sclerosis
Albuminuria
Glomerulosclerosis, Focal Segmental
Pathologic Processes
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Glomerulonephritis
Nephritis
Kidney Diseases

ClinicalTrials.gov processed this record on July 27, 2016