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

NCT02585804 | Completed Phase 4

• 1 other identifier: REB# 14-8284-B
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Focal Segmental Glomerulosclerosis

Keywords

FSGS, SGLT2, chronic kidney disease, GFR, proteinuria

Outcome Measures

Primary Outcomes (1)

• The change in Glomerular Filtration Rate (GFR) After an 8 week treatment with dapagliflozin

  Glomerular Filtration Rate (GFR, based on plasma inulin clearance) will be measured at baseline and after 8 weeks of treatment.

  Before and after an 8 week treatment with dapagliflozin

Secondary Outcomes (4)

• The change in Effective Renal Plasma Flow (ERPF) After an 8 week treatment with dapagliflozin

  Before and after an 8 week treatment with dapagliflozin

• The change in Blood Pressure After an 8 week treatment with dapagliflozin

  Before and after 8 weeks of treatment with dapagliflozin

• The change in albuminuria after 8 weeks of treatment with dapagliflozin

  Before and after 8 weeks of treatment with dapagliflozin

• The change in urinary vasoactive mediators after 8 weeks of treatment with dapagliflozin

  Before and after 8 weeks of treatment with dapagliflozin

Study Arms (1)

Dapagliflozin (trade name Farxiga®)

EXPERIMENTAL

Oral tablet, 10mg, PO, 8 weeks

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

Oral tablet, 10mg, PO, 8 weeks

Also known as: Trade name Farxiga®

Dapagliflozin (trade name Farxiga®)

Eligibility Criteria

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

You may qualify if:

• 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
• \>30 mg/day and \<6 g/day of proteinuria unless the patient is not a candidate for immunosuppressive therapy

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Health Network, Toronto: lead
• AstraZeneca: collaborator
• University of Toronto: collaborator
• Toronto General Hospital: collaborator

Study Sites (1)

Renal Physiology Laboratory, University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental; Renal Insufficiency, Chronic; Proteinuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urination Disorders; Urological Manifestations; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Clinician Scientist

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 23, 2015
• Study Start: September 1, 2015
• Primary Completion: April 24, 2017
• Study Completion: April 24, 2017
• Last Updated: January 16, 2018

Record last verified: 2018-01

Locations

CA (1)