NCT02585622终止1 期
Novel Stromal Cell Therapy for Diabetic Kidney Disease (NEPHSTROM Study)
Mario Negri Institute for Pharmacological Research4 个研究点 分布在 3 个国家目标入组 29 人开始时间: 2017年12月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 4
- 主要终点
- Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events.
研究概览
简要总结
The study will investigate, primarily, the safety, feasibility and tolerability and, secondarily, the preliminary efficacy of an allogeneic bone marrow-derived Mesenchymal Stromal Cell (MSC) therapy (ORBCEL-M) in study subjects with type 2 diabetes (T2D) and progressive diabetic kidney disease (DKD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female ≥ 40 years and <85 years old. ;
- •T2D for 3 or more years under a clinician with mandated responsibility for management of the patients to national guidelines;
- •Urinary albumin excretion (UAE) ≥ 60 µg/min (in a 24 hour urine collection) and urine albumin-to-creatinine ratio (UACR) ≥ 88 mg/g (≥ 10 mg/mmol) (in a spot morning urine collection);
- •Estimated GFR (eGFR) 30-50 ml/min/1.73 m^2 by the CKD-EPI equation on 2 or more consecutive measurements at least 30 days apart within the past 6 months;
- •A documented decline of eGFR of ≥ -10ml/min/1.73 m^2 over the past 3 years or documented rate of eGFR decline of ≥ -5 ml/min/1.73 m^2 year based on 3 or more consecutive readings at least 90 days apart in the past 18 months;
- •Lack of suspicion of renal diagnosis other than DKD;
- •Willing and able to provide written informed consent.
排除标准
- •Current resting systolic BP ≥ 150 mmHg and current resting diastolic BP ≥ 90 mmHg in a clinical setting, despite treatment with 3 hypertensive agents of different classes (including one diuretic), measured in a quiet environment with morning medications already taken;
- •Initiation of a new anti-hypertensive agent within the past 6 months
- •Increase the dose of an anti-hypertensive agent by ≥ 100% of the previous dose within the past 3 months
- •Exclusion criteria related to glycaemic control:
- •Current HbA1c > 75 mmol/mol (> 9%)
- •Initiation of a new hypoglycaemic agent within the past 6 months
- •Increase the dose of a hypoglycaemic agent by ≥ 100% of the previous dose within the past 3 months
- •Exclusion criteria related to dyslipidaemia:
- •Current fasting total cholesterol > 7 mmol/l
- •Current fasting total triglycerides > 3.5 mmol/l
- •Initiation of a new lipid lowering agent within the past 6 months
- •Other exclusion criteria:
- •Chronic lung or liver disease;
- •Cardiovascular events (myocardial infarction, stroke or acute limb ischemia) within 6 months prior to enrolment;
- •Current or history within 6 months prior to enrolment of NYHA class III or IV heart failure;
- •Other concomitant disease or conditions in the opinion of the investigator that are likely to pose risk to the patient and that would render the patient unsuitable for participation or that could impair patient safety or ability to participate in the study, such as active malignancy;
- •Irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
- •Positive screening test for clinically significant anti-HLA antibodies. An initial antibody screening with Luminex® multi-antigen beads to detect class I and class II MHC antibodies followed by a Luminex single antigen bead assay to determine the specificity of any antibody detected. Potential study subjects with positive screening for any clinically significant anti-HLA antibody will be excluded and will not be eligible to participate in the NEPHSTROM clinical study (MFI>1500);
- •History or presence of any medical condition or disease which, in the opinion of the Investigator may place the participant at unacceptable risk for study participation;
- •Childbearing potential without use of effective acceptable methods of contraception. Women of childbearing potential can only be included in the study if a pregnancy test is negative at the screening visit (V1) and at baseline visit (V2) if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least two effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical treatment such as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
- •Pregnancy or lactating;
- •Participation in other investigational medicinal product (IMP) trials within 30 days before the inclusion or concurrent to this study (18 month follow-up);
- •Inability to understand the potential risks and benefits of the study;
- •Legal incapacity.
研究组 & 干预措施
Bone marrow-derived Mesenchymal Stromal Cells
Experimental
干预措施: Mesenchymal Stromal Cells (Biological)
Cryostor CS10
Placebo Comparator
干预措施: Placebo (Other)
结局指标
主要结局
Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events.
时间窗: Changes from baseline to study completion, up to 18 months after cell or placebo infusion.
At each visit overall clinical condition of the patient will be evaluated and any adverse event wil be recorded.
次要结局
- HbA1c (target <75mmol/mol or <9%)(Proportion of study participants within target range (<75mmol/mol or <9%) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Quality of life(Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.)
- Urinary Albumin/Creatinine Ratio (ACR)(Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.)
- Total cholesterol (target <200 mg/dl)(Proportion of study participants within target range (<200 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Glomerular filtration rate (GFR)(Changes from baseline up to 18 months after cell or placebo infusion.)
- Serum/plasma concentrations (pg/ml) of biomarkers of inflammation.(Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.)
- Urinary albumin excretion (UAE).(Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.)
- Anti-HLA antibody development(Changes from baseline to 3,12 and 18 months after cell or placebo infusion.)
- Serum/plasma concentrations (ng/ml) of biomarkers of CKD progression.(Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.)
- Fasting blood glucose (target <126mg/dL)(Proportion of study participants within target range (<126mg/dL) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Triglycerides (target <170 mg/dl)(Proportion of study participants within target range (<170 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Proportion/total number of circulating T cells, B cells, NK cells, monocytes, dendritic cells(Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.)
- LDL cholesterol (target <100 mg/dl)(Proportion of study participants within target range (<100 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Arterial blood pressure (the target value <130/80 mmHg)(Proportion of study participants within target range (<130/80 mmHg)at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).)
- Inflammation and fibrosis related soluble mediators(Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.)
- Urine concentrations (pg/ml adjusted to urine creatinine concentration) of biomarkers of inflammation.(Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.)
- Cost-effectiveness of cell therapy(Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.)
研究者
研究点 (4)
Loading locations...
相似试验
进行中（未招募）
1 期
ephstrom for Diabetic Kidney DiseaseEUCTR2016-000661-23-IEIRCCS - Istituto di Ricerche Farmacologiche Mario Negri48
进行中（未招募）
1 期
ephstrom for Diabetic Kidney DiseasePatients with type 2 diabetes and clinically-diagnosed progressive diabetic kidney disease.MedDRA version: 20.1 Level: LLT Classification code 10012687 Term: Diabetic renal disease System Organ Class: 100000004857MedDRA version: 20.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disordersEUCTR2016-000661-23-GBIRCCS - Istituto di Ricerche Farmacologiche Mario Negri48
尚未招募
不适用
Establishment and Clinical Validation of a New Technique for Early Diagnosis of Diabetic NephropathyBiomarkersDiabetic Kidney DiseaseDiabetes MellitusEarly DiagnosisNCT04976426Second Affiliated Hospital, School of Medicine, Zhejiang University1,000
尚未招募
1 期
Stem Cell Derived Exome for Treatment of Diabetic FootStem CellDiabetic FootNCT06480123Second Affiliated Hospital of Guangzhou Medical University50
Unknown
1 期
A Clinical Study Using Adipose-derived Stem Cells for Diabetic FootIschemiaDiabetic FootPeripheral Vascular DiseaseNCT02831075Jie Shen240