Clinical trial NCT02693366: Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis
Official title: Safety Study of the Endovascular Infusion of Bone Marrow Derived Mononuclear Cells in Patients With Focal Segmental Glomerulosclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Focal Segmental Glomerulosclerosis
Chronic Kidney Diseases
Keywords: bone marrow cells
Focal Segmental Glomerulosclerosis
Chronic Kidney Diseases
stem cell
cell therapy
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Brazil
name: Ministry of Health, Brazil
name: National Research Council, Brazil
name: Rio de Janeiro State Research Supporting Foundation (FAPERJ)
First posted: 2016-02-26
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Kidney injury
timeFrame: 9 months
measure: Chronic kidney disease
timeFrame: 9 months
measure: Potential differentiation disorders of transplanted cells
timeFrame: 9 months
measure: Systemic inflammatory potential of mononuclear cells administration in renal circulation
timeFrame: 9 months
measure: Death
timeFrame: 9 months
Secondary outcomes:
measure: Renal function
timeFrame: 9 months
measure: Bone metabolism
timeFrame: 9 months
measure: Balance assessment electrolyte and acid-base
timeFrame: 9 months
measure: The lipid profile assessment and anemia
timeFrame: 9 months
measure: Quality of life questionnaire
timeFrame: 9 months
measure: Imaging tests
timeFrame: 9 months
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Universitary Hospital Clementino Fraga Filho - UFRJ
Study officials:
affiliation: Universidade Federal do Rio de Janeiro
name: Marcelo Marcos Morales, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References: