TerminatedNCT02585622NEPHSTROMUpdated Nov 29, 2024

NEPHSTROM for Diabetic Kidney Disease

A Phase 1/2 interventional study of Mesenchymal Stromal Cells and Placebo in Diabetic Kidney Disease, sponsored by Mario Negri Institute for Pharmacological Research. Terminated at 4 sites in 3 countries. Open to participants aged 40 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-11-29.

Sponsored by Mario Negri Institute for Pharmacological Research · Phase 1/2, Interventional, and Other

Why this study was terminated

IMP NEPHSTROM ORBECEL-M is expired and additional extension is not feasible. Low recruitment rate at Birmingham center.

Phase: Phase 1/2
Study type: Interventional
Enrollment: 29
Allocation: Randomized
Ages: 40 Years to 85 Years
Sex: All

Study 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).

Conditions studied

Diabetic Kidney Disease

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Keywords

Diabetic Kidney Disease
Mesenchymal Stromal Cells (MSC)
immune response
allogeneic
disease progression

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 29 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

Mario Negri Institute for Pharmacological Research is the lead sponsor of 159 studies on the registry; 36 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 40 Years to 85 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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:

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 29 participants (actual)

Study arms

Experimental
Bone marrow-derived Mesenchymal Stromal Cells
Biological: Mesenchymal Stromal Cells
Placebo comparator
Cryostor CS10
Other: Placebo

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
Also known as: Allogeneic Cellular Therapy (NEPHSTROM ORBCEL-M)
OtherPlacebo
Volume total of fluid infused: 40 ml
Also known as: Cryostor CS10

What researchers measure

Primary outcomes

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.

Secondary outcomes

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)
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.

Study locations

4 sites

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 24027, 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

References and documents

Publications

Perico N, Remuzzi G, Griffin MD, Cockwell P, Maxwell AP, Casiraghi F, Rubis N, Peracchi T, Villa A, Todeschini M, Carrara F, Magee BA, Ruggenenti PL, Rota S, Cappelletti L, McInerney V, Griffin TP, Islam MN, Introna M, Pedrini O, Golay J, Finnerty AA, Smythe J, Fibbe WE, Elliman SJ, O'Brien T; NEPHSTROM Trial Consortium. Safety and Preliminary Efficacy of Mesenchymal Stromal Cell (ORBCEL-M) Therapy in Diabetic Kidney Disease: A Randomized Clinical Trial (NEPHSTROM). J Am Soc Nephrol. 2023 Oct 1;34(10):1733-1751. doi: 10.1681/ASN.0000000000000189. Epub 2023 Aug 10. PubMed 37560967 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 29, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02585622
Lead sponsor: Mario Negri Institute for Pharmacological Research
Collaborators: 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
Responsible party: Sponsor
First posted: Oct 23, 2015
Start date: Dec 11, 2017
Primary completion: Nov 3, 2022
Completion: Jan 3, 2024
Last update: Nov 29, 2024

Study contacts

Giuseppe Remuzzi, MD

study chair · ASST Papa Giovanni XXIII, Bergamo, Italy/IRCCS - Mario Negri Institute for Pharmacological Research

Mattew Griffin, MD

principal investigator · National University of ireland - Galway University Hospital -Regenerative Medicine Institute

Paul Cockwell, MD

principal investigator · University Hospital Birmingham NHS Foundation Trust

Peter Maxwell, MD

principal investigator · Belfast Health and Social Care Trust - Belfast City Hospital

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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