Safety Study of the Endovascular Infusion of Bone Marrow Derived Mononuclear Cells in Patients With Focal Segmental Glomerulosclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Death
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
Death
时间窗: 9 months
Kidney injury
时间窗: 9 months
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
Chronic kidney disease
时间窗: 9 months
Doubling of serum creatinine based on the third month after the cell therapy or the need to start dialysis
Potential differentiation disorders of transplanted cells
时间窗: 9 months
Analyzed by clinical and imaging tests such abdominal ultrasound and chest radiography
Systemic inflammatory potential of mononuclear cells administration in renal circulation
时间窗: 9 months
Laboratory tests: C-reactive protein, erythrocyte sedimentation rate, blood count and urinary sediment
次要结局
- Renal function(9 months)
- Bone metabolism(9 months)
- Balance assessment electrolyte and acid-base(9 months)
- The lipid profile assessment and anemia(9 months)
- Quality of life questionnaire(9 months)
- Imaging tests(9 months)
研究者
Marcelo Marcos Morales
MD, PhD
Universidade Federal do Rio de Janeiro