Diabetic Kidney Disease
Conditions
Keywords
Diabetic Kidney Disease, Mesenchymal Stromal Cells (MSC), immune response, allogeneic, disease progression
Brief summary
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).
Interventions
BIOLOGICALMesenchymal Stromal Cells
Cells will be administered intravenously at 3 different doses (80, 160, or 240 x 10\^6, fixed dose) over 10-20 minutes. Volume total of fluid infused: 40 ml
OTHERPlacebo
Volume total of fluid infused: 40 ml
Sponsors
Leiden University Medical Center
Papa Giovanni XXIII Hospital
Istituto Di Ricerche Farmacologiche Mario Negri
Belfast Health and Social Care Trust
National University of Ireland, Galway, Ireland
University Hospital Birmingham, NHS Foundation Trust, Hospital, Birmingham, UK
NHS Blood and Transplant
Mario Negri Institute for Pharmacological Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
1. 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; 2. Initiation of a new anti-hypertensive agent within the past 6 months 3. Increase the dose of an anti-hypertensive agent by ≥ 100% of the previous dose within the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | ACR will be measured on spot morning urine samples. |
| 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. | UAE will be measured on 24h urine samples using standardized methods. |
| 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). | — |
| 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). | — |
| 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). | — |
| 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). | — |
| 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). | — |
| 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). | — |
| Glomerular filtration rate (GFR) | Changes from baseline up to 18 months after cell or placebo infusion. | GFR will be measured by plasma clearance of unlabelled exogenous marker Iohexol and estimated by CKD-EPI and MDRD equations. |
| Anti-HLA antibody development | Changes from baseline to 3,12 and 18 months 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. | Blood and urine bio-chip-based multiplex assay |
| 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. | Biomarkers will include sTNFR1, sTNFR2, Il-6,TNF-alfa, IL-1beta, MCP-1 (CCL2), IL-8, FGF21. |
| 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. | Biomarkers will include Cystatin C, NGAL, Adiponectin, Leptin. |
| 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. | Biomarkers will include sTNFR1, sTNFR2, Il-6,TNF-alfa, IL-1beta, MCP-1 (CCL2), IL-8. |
| 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. | — |
| Cost-effectiveness of cell therapy | Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion. | Cost-effectiveness of cell therapy will be evaluated by providing the patients with a healthcare resource diary. |
| Quality of life | Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion. | Quality of life will be evaluated by the administration of SF36 questionnaire. |
Countries
Ireland, Italy, United Kingdom
Outcome results
None listed