Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis (STEFOG)

Safety Study of the Endovascular Infusion of Bone Marrow Derived Mononuclear Cells in Patients With Focal Segmental Glomerulosclerosis

The purpose of this study is to analyze the safety, renal function, metabolic disorders and quality of life data in patients with focal segmental glomerulosclerosis treated with endovascular infusion of bone marrow derived mononuclear cells.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Focal Segmental Glomerulosclerosis
• Intervention / Treatment: Other: Bone marrow stem cell

Detailed Description

Will be studied five patients with progressive chronic kidney disease and estimated clearance between 40 and 20 ml / min. Patients will be followed by clinical and laboratory examination for 3 months prior to the procedure. These previous results serve as a control for comparison with a second time when the same patients receive treatment with stem cells being subsequently followed up for 9 months a total of one year of clinical follow-up.

Bone marrow aspiration and subsequent cell preparation were accomplished on the same day as the endovascular infusion of autologous Bone Marrow derived Mononuclear stem cells (BMDMCs) in both renal arteries. Collection was performed under spinal anesthesia and light sedation, through puncture and repeated aspirations at the posterior iliac crest region. A total of 80 mL of bone marrow aspirate was collected from each patient, and after removal of bone and fatty residues, mononuclear cells were isolated by a Ficoll-Paque Plus (Amersham Biosciences, São Paulo, Brazil).For each patient, 2×107 cells will be labeled with 99mTc. Briefly, 500 μl of sterile SnCl2 solution is added to the cells and the mixture is incubated at room temperature for 10 min. Forty-five millicurie (mCi) of 99mTc is then added and incubation continued for another 10 min. After centrifugation (500×g for 5 min), the supernatant is removed and the cells are washed in saline solution. The pellet will be also resuspended in saline solution. Viability of the labeled cells will be assessed by the trypan blue exclusion test, and estimated to be greater than 93% in all cases.The labeling efficiency (%) will be calculated by the activity in the pellet divided by the sum of the radioactivity in the pellet plus supernatant and estimated to be greater than 90% in all cases.

After the collection of the stem cells, the patient will be submitted to puncture the femoral artery using the Seldinger technique under local anesthesia, followed by catheterization of the ostium of the renal arteries with minimum use of nonionic iodinated contrast. With the routing of diagnostic catheter or guide, the solution numbering about 30 to 100 million of dissolved plasma cells will be divided and injected into two renal arteries. The infusion volume is about 5 ml in each kidney. Whole body and planar scans will be performed 2 and 24h after infusion to determine the migration and cell viability. The patient will remain hospitalized for more 48 hours for clinical monitoring and collection of laboratorial tests.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21941913
    • Universitary Hospital Clementino Fraga Filho - UFRJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with diagnosis of primary focal segmental glomerulosclerosis after having been previously treated with corticosteroids and immunosuppressive drugs and have not reached satisfactory answer. Will also be considered candidates those patients who performed late diagnosis and therefore no more clinical indication to perform therapy with corticosteroids and immunosuppressants. In both cases, showing irreversible loss of renal function with filtration rate between 40 - 20 ml/min.
• Patient should use the classical nephroprotective medication: angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or both.

Exclusion Criteria:

• Acute urinary tract infection;
• Urinary infection with tuberculosis bacillus or fungi;
• Patients with poorly anatomical formations of the urinary tract, polycystic kidney disease and other congenital or acquired kidney diseases.
• Blood pressure greater than 160 mm Hg systolic and 100 mmHg diastolic, in measurements taken during the last 3 outpatient visits;
• Who has performed examination with iodinated contrast the last 3 months
• Use of potentially nephrotoxic drugs;
• Use of corticosteroid therapy in immunosuppressive doses or more than 0.3 mg/kg/day
• Inability to obtain vascular access for endovascular procedure
• Sepsis (defined according to the Society of Critical Care Medicine, American College of Chest Physicians, 1992);
• Malignancies
• Autoimmune disorders,
• Neurodegenerative diseases;
• Acute heart failure or decompensated;
• Primary hematologic diseases;
• Osteopathies reflecting increased risk for spinal puncture;
• Coagulopathies;
• Liver failure;
• History of stroke or myocardial infarction in the last 6 months;
• Pregnancy or breastfeeding;
• History and serology of chronic infectious diseases, including HIV, Hepatitis C virus, Hepatitis B virus
• Participation in another clinical trial last year
• Cognitive impairment to understand all procedures
• Prolonged travel plans or domicile changes to other states that generate unable to attend the follow-up visits;
• Any other clinically significant active disease in the opinion of the principal investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Autologous Cell Therapy; We are conducting a prospective, non-randomized, single-center longitudinal study in five patients with progressive chronic kidney disease and estimated clearance between 40 and 20 ml / min. Patients will be followed by clinical and laboratory examination for 3 months prior to the procedure. These previous results serve as a control for comparison with a second time when the same patients receive treatment with stem cells being subsequently followed up for 9 months a total of one year of clinical follow-up.

Other: Bone marrow stem cell; Endovascular infusion of bone marrow derived cells in both renal arteries.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney injury	Increase of serum creatinine of about 0.5 mg / dL when levels are less than 3.0 mg / dl and 1.0 mg / dl baseline levels when are greater than or equal to 3.0 mg / dL) when confirmed with the second examination.; Acute: evaluated within 15 days of cell therapy;; Subacute: evaluated 15-90 days of cell therapy	9 months
Chronic kidney disease	Doubling of serum creatinine based on the third month after the cell therapy or the need to start dialysis	9 months
Potential differentiation disorders of transplanted cells	Analyzed by clinical and imaging tests such abdominal ultrasound and chest radiography	9 months
Systemic inflammatory potential of mononuclear cells administration in renal circulation	Laboratory tests: C-reactive protein, erythrocyte sedimentation rate, blood count and urinary sediment	9 months
Death		9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function	The estimated creatinine clearance assessment by MDRD formula	9 months
Bone metabolism	Evaluation of bone metabolism by serum phosphorus (mg/dL), calcium (mg/dL), parathormone (pg/ml), 25 (OH) vit. D (ng/ml).	9 months
Balance assessment electrolyte and acid-base	Balance assessment electrolyte and acid-base by serum sodium (mEq/l), potassium (mEq/l), uric acid (mg/dl) and bicarbonate	9 months
The lipid profile assessment and anemia	The lipid profile assessment (LDL- cholesterol, HDL-cholesterol and triglyceride) and anemia measured by hemoglobin (g/dL) and hematocrit.	9 months
Quality of life questionnaire	Clinical improvement of the patient, with subjective assessment of general health and well being through SF36 quality of life questionnaire	9 months
Imaging tests	Imaging tests: Renal scintigraphy with 99mTc-DTPA and DMSA	9 months

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Collaborators: Ministry of Health, Brazil; Rio de Janeiro State Research Supporting Foundation (FAPERJ); National Research Council, Brazil; Ministry of Science and Technology, Brazil
• Investigators: Principal Investigator: Marcelo Marcos Morales, MD,PHD, Universidade Federal do Rio de Janeiro

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: January 30, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 26, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: cell therapy; stem cell; Focal Segmental Glomerulosclerosis; Chronic Kidney Diseases; bone marrow cells
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Nephritis; Glomerulonephritis; Kidney Diseases; Renal Insufficiency, Chronic; Glomerulosclerosis, Focal Segmental
• Other Study ID Numbers: CAAE:01498412.5.0000.5257

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided