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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
29
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
Volume total of fluid infused: 40 ml
National University of ireland - Galway University Hospital -Regenerative Medicine Institute
Galway, Ireland
ASST - Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/ Mario Negri Institute for Pharmacological Research - Clinical Research Center for Rare Diseases Aldo e Cele Daccò
Bergamo, BG, Italy
Belfast Health and Social Care Trust - Belfast City Hospital
Belfast, United Kingdom
University Hospital Birmingham NHS Foundation Trust - Queen Elizabeth Medical Centre
Birmingham, United Kingdom
Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events.
At each visit overall clinical condition of the patient will be evaluated and any adverse event wil be recorded.
Time frame: Changes from baseline to study completion, up to 18 months after cell or placebo infusion.
Glomerular filtration rate (GFR)
GFR will be measured by plasma clearance of unlabelled exogenous marker Iohexol and estimated by CKD-EPI and MDRD equations.
Time frame: Changes from baseline up to 18 months after cell or placebo infusion.
Urinary Albumin/Creatinine Ratio (ACR)
ACR will be measured on spot morning urine samples.
Time frame: Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.
Urinary albumin excretion (UAE).
UAE will be measured on 24h urine samples using standardized methods.
Time frame: Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.
Fasting blood glucose (target <126mg/dL)
Time frame: 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%)
Time frame: 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)
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Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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).
Quality of life
Quality of life will be evaluated by the administration of SF36 questionnaire.
Time frame: Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.
Quality of life
Quality of life will be evaluated by the administration of EQ-5D-5L questionnaire.
Time frame: Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.
Anti-HLA antibody development
Time frame: Changes from baseline to 3,12 and 18 months after cell or placebo infusion.
Inflammation and fibrosis related soluble mediators
Blood and urine bio-chip-based multiplex assay
Time frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.
Serum/plasma concentrations (pg/ml) of biomarkers of inflammation.
Biomarkers will include sTNFR1, sTNFR2, Il-6,TNF-alfa, IL-1beta, MCP-1 (CCL2), IL-8, FGF21.
Time frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.
Serum/plasma concentrations (ng/ml) of biomarkers of CKD progression.
Biomarkers will include Cystatin C, NGAL, Adiponectin, Leptin.
Time frame: 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.
Biomarkers will include sTNFR1, sTNFR2, Il-6,TNF-alfa, IL-1beta, MCP-1 (CCL2), IL-8.
Time frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.
Proportion/total number of circulating T cells, B cells, NK cells, monocytes, dendritic cells
Time frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.
Cost-effectiveness of cell therapy
Cost-effectiveness of cell therapy will be evaluated by providing the patients with a healthcare resource diary.
Time frame: Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.