<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03840343</url>
  </required_header>
  <id_info>
    <org_study_id>18-002423</org_study_id>
    <secondary_id>RMM 091718 CT 001</secondary_id>
    <nct_id>NCT03840343</nct_id>
  </id_info>
  <brief_title>Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease</brief_title>
  <official_title>Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regenerative Medicine Minnesota</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Researchers will assess the safety, tolerability, dosing effect, and early signals of&#xD;
      efficacy of intra-arterially delivered autologous (from self) adipose (fat) tissue-derived&#xD;
      mesenchymal stem/stromal cells (MSC) in patients with progressive diabetic kidney disease&#xD;
      (DKD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, open-label dose-escalating study assessing safety, tolerability,&#xD;
      dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from&#xD;
      self) adipose tissue-derived mesenchymal stem/stromal cells (MSC) in 30 patients with&#xD;
      progressive diabetic kidney disease (DKD). DKD will be defined as chronic kidney disease&#xD;
      (CKD; estimated glomerular filtration rate; eGFR&lt;60 mL/min/1.73m2) in the setting of diabetes&#xD;
      mellitus (type 2; on anti-diabetes therapy) without overt etiologies of CKD beyond&#xD;
      concomitant hypertension. Progressive DKD will be considered as eGFR 25-55 ml/min/1.73m2 with&#xD;
      a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or&#xD;
      high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on&#xD;
      the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney&#xD;
      failure risk equation. Fifteen subjects will be placed in one of two cell dosage arms in a&#xD;
      parallel design with single-kidney MSC administration at Day 0 and Month 3. Subjects will be&#xD;
      followed a total of 15 months from time of initial cell administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Principal Investigator relocation&#xD;
  </why_stopped>
  <start_date type="Actual">October 23, 2019</start_date>
  <completion_date type="Actual">August 4, 2020</completion_date>
  <primary_completion_date type="Actual">August 4, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Baseline through Month 15</time_frame>
    <description>The number of Adverse Events associated with MSC intervention per treatment arm</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Baseline through Month 15</time_frame>
    <description>The percentage of Adverse Events associated with MSC intervention per treatment arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kidney Function</measure>
    <time_frame>baseline, month 6</time_frame>
    <description>Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Function</measure>
    <time_frame>pretreatment, month 12</time_frame>
    <description>Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Diabetic Kidney Disease</condition>
  <condition>Diabetic Nephropathies</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Diabetes Mellitus, Type 1</condition>
  <condition>Chronic Kidney Disease</condition>
  <condition>Diabetic Nephropathy Type 2</condition>
  <condition>Kidney Failure</condition>
  <condition>Kidney Insufficiency</condition>
  <arm_group>
    <arm_group_label>Lower Dose MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Higher Dose MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose</intervention_name>
    <description>Two MSC infusions of 2.5x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery</description>
    <arm_group_label>Lower Dose MSC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose</intervention_name>
    <description>Two MSC infusions of 5.0x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery</description>
    <arm_group_label>Higher Dose MSC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diabetes mellitus (on anti-diabetes drug therapy)&#xD;
&#xD;
          -  Age 45-75 years&#xD;
&#xD;
          -  eGFR 25-55 ml/min/1.73m2 at time of consent with: a) eGFR decline of 5 ml/min over 18&#xD;
             months or 10 ml/min over 3 years or b) an intermediate or high 5-year risk of&#xD;
             progression to end-stage kidney failure (dialysis or transplant) based on the&#xD;
             validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney&#xD;
             failure risk equation https://kidneyfailurerisk.com/&#xD;
&#xD;
          -  Primary cause of kidney disease is diabetes without suspicion of concomitant kidney&#xD;
             disease beyond hypertension&#xD;
&#xD;
          -  Spot urine albumin:creatinine ≥30 mg/g unless on RAAS inhibition&#xD;
&#xD;
          -  Ability to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemoglobin A1c≥11%&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Active Immunosuppression therapy&#xD;
&#xD;
          -  Kidney transplantation history&#xD;
&#xD;
          -  Concomitant glomerulonephritis&#xD;
&#xD;
          -  Nephrotic syndrome&#xD;
&#xD;
          -  Solid organ transplantation history&#xD;
&#xD;
          -  Autosomal dominant or recessive polycystic kidney disease&#xD;
&#xD;
          -  Known renovascular disease&#xD;
&#xD;
          -  Kidney failure (hemodialysis, peritoneal dialysis, or kidney transplantation)&#xD;
&#xD;
          -  Active tobacco use&#xD;
&#xD;
          -  Body weight &gt;150 kg or BMI&gt;50&#xD;
&#xD;
          -  Uncontrolled hypertension: Systolic blood pressure (SBP) &gt;180 mmHg despite&#xD;
             antihypertensive therapy&#xD;
&#xD;
          -  Recent cardiovascular event (myocardial infarction, stroke, congestive heart failure&#xD;
             within 6 months&#xD;
&#xD;
          -  Evidence of hepatitis B or C, or HIV infection, chronic&#xD;
&#xD;
          -  Anticoagulation therapy requiring heparin bridging for procedures.&#xD;
&#xD;
          -  History of methicillin-resistant staphylococcus aureus colonization&#xD;
&#xD;
          -  Recent plastic, chemical or surgical manipulation of adipose tissue for cosmetic&#xD;
             purposes within 6 months&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
&#xD;
          -  Potentially unreliable subjects and those judged by the investigator to be unsuitable&#xD;
             for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>LaTonya J Hickson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials/cls-20438442</url>
    <description>Diabetic Kidney Disease Stem Cell Trial - Mayo Clinic</description>
  </link>
  <link>
    <url>https://regenerativemedicineblog.mayoclinic.org/2018/10/26/stem-cells-and-chronic-kidney-disease/</url>
    <description>Stem Cells and Kidney Disease - Mayo Clinic</description>
  </link>
  <link>
    <url>https://youtu.be/DQ7r3UFMDN8</url>
    <description>Video of Stem Cell Trial in Diabetic Kidney Disease - Regenerative Medicine Minnesota</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>LaTonya J. Hickson</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Mesenchymal Stem Cell</keyword>
  <keyword>Mesencymal Stromal Cell</keyword>
  <keyword>Stem Cell</keyword>
  <keyword>Regenerative Medicine</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>Rejuvenation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03840343
org study id: 18-002423
secondary id: RMM 091718 CT 001
nct id: NCT03840343
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The Researchers will assess the safety, tolerability, dosing effect, and early signals of
      efficacy of intra-arterially delivered autologous (from self) adipose (fat) tissue-derived
      mesenchymal stem/stromal cells (MSC) in patients with progressive diabetic kidney disease
      (DKD).
This is a single center, open-label dose-escalating study assessing safety, tolerability,
      dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from
      self) adipose tissue-derived mesenchymal stem/stromal cells (MSC) in 30 patients with
      progressive diabetic kidney disease (DKD). DKD will be defined as chronic kidney disease
      (CKD; estimated glomerular filtration rate; eGFR<60 mL/min/1.73m2) in the setting of diabetes
      mellitus (type 2; on anti-diabetes therapy) without overt etiologies of CKD beyond
      concomitant hypertension. Progressive DKD will be considered as eGFR 25-55 ml/min/1.73m2 with
      a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or
      high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on
      the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney
      failure risk equation. Fifteen subjects will be placed in one of two cell dosage arms in a
      parallel design with single-kidney MSC administration at Day 0 and Month 3. Subjects will be
      followed a total of 15 months from time of initial cell administration.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: Baseline through Month 15
description: The number of Adverse Events associated with MSC intervention per treatment arm
measure: Adverse Events
time frame: Baseline through Month 15
description: The percentage of Adverse Events associated with MSC intervention per treatment arm
measure: Kidney Function
time frame: baseline, month 6
description: Change in measured glomerular filtration rate (mGFR). Measured as mL/min/BSA
measure: Kidney Function
time frame: pretreatment, month 12
description: Change in estimated glomerular filtration rate (eGFR) slope. Measured as mL/min/1.73m^2/month
arm group label: Lower Dose MSC
arm group type: Experimental
description: This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Lower Dose.
arm group label: Higher Dose MSC
arm group type: Experimental
description: This arm will receive autologous adipose-derived Mesenchymal stem/stromal cells (MSC) Higher Dose
intervention type: Biological
intervention name: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Lower Dose
description: Two MSC infusions of 2.5x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
arm group label: Lower Dose MSC
intervention type: Biological
intervention name: Autologous adipose-derived mesenchymal stem/stromal cells (MSC) Higher Dose
description: Two MSC infusions of 5.0x10^5 cells/kg at time zero and three months; single kidney, intra-arterial delivery
arm group label: Higher Dose MSC
criteria: 
gender: All
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: No
last name: LaTonya J Hickson, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials/cls-20438442
description: Diabetic Kidney Disease Stem Cell Trial - Mayo Clinic
url: https://regenerativemedicineblog.mayoclinic.org/2018/10/26/stem-cells-and-chronic-kidney-disease/
description: Stem Cells and Kidney Disease - Mayo Clinic
url: https://youtu.be/DQ7r3UFMDN8
description: Video of Stem Cell Trial in Diabetic Kidney Disease - Regenerative Medicine Minnesota
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: LaTonya J. Hickson
investigator title: Principal Investigator
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Renal Insufficiency
mesh term: Diabetic Nephropathies
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No