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Trial record 15 of 7202 for:    "Kidney Diseases"

NEPHSTROM for Diabetic Kidney Disease (NEPHSTROM)

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ClinicalTrials.gov Identifier: NCT02585622
Recruitment Status : Recruiting
First Posted : October 23, 2015
Last Update Posted : March 21, 2018
Sponsor:
Collaborators:
Leiden University Medical Center
ASST Papa Giovanni XXIII, Bergamo, Italy
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri - Bergamo, Italy
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
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

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).

Condition or disease Intervention/treatment Phase
Diabetic Kidney Disease Biological: Mesenchymal Stromal Cells Other: Placebo Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Novel Stromal Cell Therapy for Diabetic Kidney Disease (NEPHSTROM Study)
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Bone marrow-derived Mesenchymal Stromal Cells Biological: Mesenchymal 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
Other Name: Allogeneic Cellular Therapy (NEPHSTROM ORBCEL-M)
Placebo Comparator: Cryostor CS10 Other: Placebo
Volume total of fluid infused: 40 ml
Other Name: Cryostor CS10



Primary Outcome Measures :
  1. Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events. [ Time Frame: 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 Outcome Measures :
  1. Glomerular filtration rate (GFR) [ Time Frame: 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.

  2. Urinary Albumin/Creatinine Ratio (ACR) [ 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. ]
    ACR will be measured on spot morning urine samples.

  3. Urinary albumin excretion (UAE). [ 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. ]
    UAE will be measured on 24h urine samples using standardized methods.

  4. 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). ]
  5. 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). ]
  6. 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). ]
  7. 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). ]
  8. 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). ]
  9. 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). ]
  10. Quality of life [ Time Frame: 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.

  11. Quality of life [ Time Frame: 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 EQ-5D-5L questionnaire.

  12. Anti-HLA antibody development [ Time Frame: Changes from baseline to 3,12 and 18 months after cell or placebo infusion. ]
  13. Inflammation and fibrosis related soluble mediators [ Time Frame: 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

  14. Serum/plasma concentrations (pg/ml) of biomarkers of inflammation. [ Time Frame: 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.

  15. Serum/plasma concentrations (ng/ml) of biomarkers of CKD progression. [ Time Frame: 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.

  16. Urine concentrations (pg/ml adjusted to urine creatinine concentration) of biomarkers of inflammation. [ Time Frame: 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.

  17. 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. ]
  18. Cost-effectiveness of cell therapy [ Time Frame: 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.



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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  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

    Exclusion criteria related to glycaemic control:

  4. Current HbA1c > 75 mmol/mol (> 9%)
  5. Initiation of a new hypoglycaemic agent within the past 6 months
  6. Increase the dose of a hypoglycaemic agent by ≥ 100% of the previous dose within the past 3 months

    Exclusion criteria related to dyslipidaemia:

  7. Current fasting total cholesterol > 7 mmol/l
  8. Current fasting total triglycerides > 3.5 mmol/l
  9. Initiation of a new lipid lowering agent within the past 6 months

    Other exclusion criteria:

  10. Chronic lung or liver disease;
  11. Cardiovascular events (myocardial infarction, stroke or acute limb ischemia) within 6 months prior to enrolment;
  12. Current or history within 6 months prior to enrolment of NYHA class III or IV heart failure;
  13. 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;
  14. Irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
  15. 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);
  16. 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;
  17. 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.
  18. Pregnancy or lactating;
  19. Participation in other investigational medicinal product (IMP) trials within 30 days before the inclusion or concurrent to this study (18 month follow-up);
  20. Inability to understand the potential risks and benefits of the study;
  21. Legal incapacity.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02585622


Contacts
Contact: Giuseppe Remuzzi, MD 003903542131 giuseppe.remuzzi@marionegri.it

Locations
Ireland
National University of ireland - Galway University Hospital -Regenerative Medicine Institute Recruiting
Galway, Ireland
Contact: Matthew Griffin, MD    00353 91 495107    matthew.griffin@nuigalway.ie   
Italy
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 Recruiting
Bergamo, BG, Italy, 24027
Contact: Giuseppe Remuzzi, MD    0039 035 45351    giuseppe.remuzzi@marionegri.it   
United Kingdom
Belfast Health and Social Care Trust - Belfast City Hospital Recruiting
Belfast, United Kingdom
Contact: Peter Maxwell, MD    0044 28 95049751    peter.maxwell@belfasttrust.hscni.net.as   
University Hospital Birmingham NHS Foundation Trust - Queen Elizabeth Medical Centre Recruiting
Birmingham, United Kingdom
Contact: Paul Cockwell, MD    0044 121 3714181    paul.cockwell@uhb.nhs.uk   
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Leiden University Medical Center
ASST Papa Giovanni XXIII, Bergamo, Italy
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri - Bergamo, Italy
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
Investigators
Study Chair: Giuseppe Remuzzi, MD ASST Papa Giovanni XXIII, Bergamo, Italy/IRCCS - Mario Negri Institute for Pharmacological Research
Principal Investigator: Mattew Griffin, MD National University of ireland - Galway University Hospital -Regenerative Medicine Institute
Principal Investigator: Paul Cockwell, MD University Hospital Birmingham NHS Foundation Trust
Principal Investigator: Peter Maxwell, MD Belfast Health and Social Care Trust - Belfast City Hospital

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT02585622     History of Changes
Other Study ID Numbers: NEPHSTROM
2016-000661-23 ( EudraCT Number )
First Posted: October 23, 2015    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mario Negri Institute for Pharmacological Research:
Diabetic Kidney Disease
Mesenchymal Stromal Cells (MSC)
immune response
allogeneic
disease progression

Additional relevant MeSH terms:
Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases