Evaluation of Therapeutic Potential of Stromal Vascular Fraction (Autologous Adipose Derived Mesenchymal Stem Cell) Based Treatment for Chronic Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Change from baseline to 24 week visit in need for dialysis in patients with CKD 5 - for phase II
研究概览
简要总结
- To assess the safety of stromal vascular fraction (Autologous Non-Expanded ADSC) injection in patients with Chronic Kidney Disease (CKD).
- To assess the efficacy of stromal vascular fraction (Autologous Non-Expanded ADSC) injection in patients with Chronic Kidney Disease (CKD).
详细描述
Introduction:
Chronic kidney disease (CKD) is a disease of alarmingly increasing prevalence (8 - 16%) associated with mortality [1]. CKD can progress towards end-stage renal disease (ESRD), requiring renal replacement therapy. ESRD currently accounts for 6.3% of Medicare spending in the United States and is projected to increase by 85% by 2015 [2]. In a study conducted among the rural populations in Bangladesh overall CKD prevalence was found about 19% [3]. Furthermore, ESRD has a major impact on quality of life and life expectancy [4]. Therefore, it is very important to develop therapeutic interventions to prevent, alleviate, or decelerate the progression of renal failure.
Diabetes mellitus and hypertension represent major causes of CKD and initiation of dialysis [5]. In addition, glomerular diseases, malnutrition, infectious diseases, and acute kidney injury may lead to ESRD, contributing to the increased global burden of death [6]. Current treatment modalities often fail to target the major underlying contributors to the progression of renal disease [7]. Management of CKD at present mostly aims at control of the predisposing factors and supplementation of kidney homeostatic functions but not at the treatment of the diseased kidney itself. Again due to lack of adequate facilities or financial constraints people of a developing country like Bangladesh are unable to continue long-term or lifelong dialysis. Chronic glomerular and tubule-interstitial fibrosis is a common pathway to ESRD, often associated with apoptosis, oxidative damage, fibrosis, and microvascular rarefaction. Unfortunately, the regenerative potential of kidneys is limited under chronic conditions and inefficient to prevent progressive glomerulosclerosis and tubule-interstitial fibrosis [8]. Treatment strategies that boost cellular regeneration might therefore offer good alternatives for patients with CKD.
Stromal vascular fraction (SVF):
SVF of adipose tissue is a rich source of pre-adipocytes, mesenchymal stem cells (MSC), endothelial progenitor cells, T cells, B cells, mast cells as well as adipose tissue macrophages [9,10]. SVF is a component of the lipo-aspirate obtained from liposuction of subcutaneous tissue. Lipo-aspirate contains a large population of stem cells called adipose-derived stem cells (ADSCs), which share a number of similarities with bone marrow stem cells, including the capacity for multilineage differentiation.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A patient is eligible for the study if all of the followings apply:
- •Aged 18-80 years (inclusive)
- •With chronic kidney disease (CKD)stage 3 to 5 (eGFR 60 to 0 mL/min/1.73m2 (inclusive)) Note : eGFR = estimated glomerular filtration rate
- •Having provided informed written consent.
排除标准
- •Any patient meeting any of the exclusion criteria will be excluded from study participation.
- •Known hypersensitivity to any component used in the study.
- •With inadequate hematologic function with: absolute neutrophil count (ANC) <1,500/μL OR platelets < 100,000/μL OR Hemoglobin < 8 g/dL
- •With impaired hepatic function with: serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AKP), prothrombin time above and normal reference and serum albumin below normal reference range.
- •With hemoglobin A1c (HbA1c) > 8.0%
- •With serious prior or ongoing medical conditions (e.g. concomitant illness such as cardiovascular (e.g. New York Heart Association grade III or IV), hepatic e.g. Child-Pugh Class C), psychiatric condition, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely effect the safety of the patient
- •Pregnant or lactating women or premenopausal with childbearing potential but not taking reliable contraceptive method(s) during the study period
- •With known history of human immunodeficiency virus (HIV) infection or any type of hepatitis
- •Judged to be not applicable to this study by investigator such as difficulty of follow-up observation
- •With any other serious diseases/medical history considered by the investigator not in the condition to enter the trial
- •Known or suspected abuse of alcohol or narcotics
- •With known history of cancer within past 5 years
- •With any autoimmune disease
- •With congenital kidney disease
- •With precancerous condition or with raised tumour markers like Alpha feto protein, Carcino embryonic antigen (CEA), C.A 19.9, C.A 125, Serum PSA above normal reference range.
- •Parcipants having a harvested total "Adipose Derived Stem Cell (ADSC)" count (in 5 ml SVF solution) less than 1 x 10^6 will be excluded from the study.
结局指标
主要结局
Change from baseline to 24 week visit in need for dialysis in patients with CKD 5 - for phase II
时间窗: Weeks 0, 2, 4, 12, 24
Need for dialysis is described as 1. No dialysis needed - Score 0 2. Randomly (more than 6 days interval) - Score 1 3. At 6 (six) days interval / Once weekly - Score 2 4. At 5 (five) days interval - Score 3 5. At 4 (four) days interval - Score 4 6. At 3 (three) days interval / 2 times a week - Score 5 7. At 2 (two) days interval - Score 6 8. At 1 (one) day interval / every alternate day./ 3 times a week - Score 7
Change from baseline to 24 week visit in glomerular filtration rate (GFR) and split renal function in all patients - for Phase II
时间窗: Weeks 0, 24
GFR with split renal function will be evaluated using DTPA Renogram.
Change from baseline to 24 week visit in estimated glomerular filtration rate (eGFR) with serum creatinine level in patients with CKD 4 and below - for Phase II
时间窗: Weeks 0, 2, 4, 12, 24
eGFR will be calculated by Serum Creatinine level using MRDR formula during all visits.
Incidence of minor adverse events (MAEs) , serious adverse events (SAEs) which may be immediate, early or late - for Phase I
时间窗: Week 48
Minor adverse events (MAEs): 1. Pain from lipo-suction \> 7 days (Early) 2. Fever \> 7 days (Early) 3. Subcutaneous hematoma / abscess formation (Early) 4. Allergic reaction (Immediate) Serious adverse events (SAEs) 1. Anaphylaxis (Immediate) 2. Pulmonary embolism or infarction (Immediate) 3. Outset of any neoplastic change (Late) 4. Outset of new Cardiovascular events (Late) 5. Outset of new Cerebrovascular or neurological events (Late) 6. Reactivation of treated tuberculosis (Late)
次要结局
- Change from baseline to all post-treatment visits in hemoglobin A1c(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to post-treatment level of serum Alpha Feto Protein(Weeks 0, 24, 48)
- Change from baseline to post-treatment level LDH level(Weeks 0, 24, 48)
- Change from baseline to all post-treatment visits in S.creatinine(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in Hemoglobin level(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in random blood sugar (RBS)(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to post-treatment visits in urine total protein-creatinine ratio (UPCR)(Weeks 0, 24, 48)
- Change from baseline to all post-treatment visits in body weight(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in Blood-pressure(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in urine microalbumin-to-creatinine ratio (UMCR)(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in Hypoglycemic agent if there is any.(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to all post-treatment visits in urinary Protein-to-creatinine ratio PCR)(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to post-treatment level of serum CEA level(Weeks 0, 24, 48)
- Change from baseline to post-treatment level of Beta 2 Microglobulin level(Weeks 0, 24,48)
- Change from baseline to post-treatment level of PSA level (in case of male patients)(Weeks 0, 24,48)
- Change from baseline to all post-treatment visits in blood urea.(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to post-treatment level of serum CA 125 level (in case of female patients)(Weeks 0, 24, 48)
- Change from baseline to all post-treatment visits in Anti-Hypertensive medication if there is any.(Weeks 0, 2, 4, 12, 24, 36, 48)
- Change from baseline to post-treatment level of serum CA 19.9 level(Weeks 0, 24, 48)