<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/NCT01719640</url>
  </required_header>
  <id_info>
    <org_study_id>MSC-MC-DM</org_study_id>
    <nct_id>NCT01719640</nct_id>
  </id_info>
  <brief_title>MSC and MC in Type 2 Diabetes Mellitus</brief_title>
  <official_title>Autologous Bone Marrow Mesenchymal Stem Cell and Bone Marrow Mononuclear Cell Infusion in Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fuzhou General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fuzhou General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cell injury in human islets induced by non-immune mediated inflammation occur in vitro upon&#xD;
      hyperglycemia in type 2 diabetes mellitus. Infusion of autologous bone marrow mononuclear&#xD;
      cells (MCs) is an emerging therapeutic approach for DM, which showed promising outcomes with&#xD;
      mild side effects. Infusion of MCs and autologous bone marrow mesenchymal stem cells in&#xD;
      combination might exert enhanced repairing effects. We hypothesized that infusion of these&#xD;
      two classes of cells might provide multiple signals for regeneration and improve recovery&#xD;
      from inflammation-induced lesion. The effects might be maximized by intra-arterial pancreatic&#xD;
      infusion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2011</start_date>
  <completion_date type="Actual">January 2020</completion_date>
  <primary_completion_date type="Actual">January 2013</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>macrovascular complications</measure>
    <time_frame>8 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>microvascular complications</measure>
    <time_frame>8 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>DPN</measure>
    <time_frame>8 years</time_frame>
    <description>diabetes peripheral neuropathy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MI</measure>
    <time_frame>8 years</time_frame>
    <description>myocardial infarction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>angina</measure>
    <time_frame>8 years</time_frame>
    <description>angina</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>stroke</measure>
    <time_frame>8 years</time_frame>
    <description>stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>amputation</measure>
    <time_frame>8 years</time_frame>
    <description>amputation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DN</measure>
    <time_frame>8 years</time_frame>
    <description>diabetes nephropathy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DRP</measure>
    <time_frame>8 years</time_frame>
    <description>diabetes retinopathy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pro-DRP</measure>
    <time_frame>8 years</time_frame>
    <description>proliferative diabetes retinopathy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-peptide AUC</measure>
    <time_frame>1y</time_frame>
    <description>C-peptide area under the curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insulin AUC</measure>
    <time_frame>1y</time_frame>
    <description>insulin area under the curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>1y</time_frame>
    <description>glycated hemoglobin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FBG</measure>
    <time_frame>1y</time_frame>
    <description>fasting hemoglucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insuline dose</measure>
    <time_frame>1y</time_frame>
    <description>exogenous insulin requirements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fasting C-p</measure>
    <time_frame>1y</time_frame>
    <description>fasting c-peptide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of adverse events related to the stem cell infusion procedure</measure>
    <time_frame>8y</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>MSC+MC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>infusion of BMMSC+BMMNC and insulin injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>infusion of BMMNC and insulin injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>insulin injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>infusion of MSCs</intervention_name>
    <description>infusion of MSCs</description>
    <arm_group_label>MSC+MC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>infusion MCs</intervention_name>
    <description>infusion of MCs</description>
    <arm_group_label>MC</arm_group_label>
    <arm_group_label>MSC+MC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin</intervention_name>
    <description>intensive insulin care</description>
    <arm_group_label>Insulin</arm_group_label>
    <arm_group_label>MC</arm_group_label>
    <arm_group_label>MSC+MC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide written informed consent.&#xD;
&#xD;
          -  Mentally stable and able to comply with the procedures of the study protocol.&#xD;
&#xD;
          -  Clinical history compatible with type 2 diabetes (T2DM) as defined by the Expert&#xD;
             Committee on the Diagnosis and classification of Diabetes Mellitus&#xD;
&#xD;
          -  Onset of T2DM disease at ≥ 35 years of age.&#xD;
&#xD;
          -  T2DM duration ≥ 3 and ≤ 20 years at the time of enrollment.&#xD;
&#xD;
          -  Basal C-peptide 0.3-2.0 ng/mL&#xD;
&#xD;
          -  HbA1c ≥ 7.5 and ≤ 12% before standard medical therapy (SMT). Patients must have been&#xD;
             treated with SMT for minimum of 4 months prior to randomization.&#xD;
&#xD;
        Insulin dose and metformin doses should be stable over the 3 months prior to randomization.&#xD;
&#xD;
          -  HbA1c ≥ 7.5 and ≤ 9.5% at time of randomization.&#xD;
&#xD;
          -  Total insulin daily dose (TDD) at time of randomization should not exceed 1.0&#xD;
             units/day/kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt;35 kg/m2.&#xD;
&#xD;
          -  Insulin requirements of &gt; 100 U/day.&#xD;
&#xD;
          -  HbA1c &gt;9.5%. (at the time of randomization)&#xD;
&#xD;
          -  C-reactive protein (hs-CRP) &gt;3.00&#xD;
&#xD;
          -  Uncontrolled blood Pressure: SBP &gt;160 mmHg or DBP &gt;100 mmHg at the time of&#xD;
             randomization.&#xD;
&#xD;
          -  Evidence of renal dysfunction, serum creatinine &gt; 1.5 mg/dl (males) and 1.4 mg/dl&#xD;
             (females).&#xD;
&#xD;
          -  Proteinuria &gt; 300 mg/day&#xD;
&#xD;
          -  Evidence of cardiovascular disease, existing congestive cardiac failure on physical&#xD;
             exam and/or acute coronary syndrome in past 6 months.&#xD;
&#xD;
          -  For female participants: Positive pregnancy test, presently breast-feeding, or&#xD;
             unwillingness to use effective contraceptive measures for the duration of the&#xD;
             study.For male participants: intent to procreate 3 months before or after the&#xD;
             intervention or unwillingness to use effective measures of contraception. Oral&#xD;
             contraceptives,Norplant®, Depo-Provera®, and barrier devices with spermicide are&#xD;
             acceptable contraceptive methods; condoms used alone are not acceptable&#xD;
&#xD;
          -  Active infection including hepatitis C, HIV, or TB as determined by a positive skin&#xD;
             test or clinical presentation, or under treatment for suspected TB. Positive tests are&#xD;
             acceptable only if associated with a history of previous vaccination in the absence of&#xD;
             any sign of active infection. Positive tests are otherwise not acceptable, even in the&#xD;
             absence of any active infection at the time of evaluation&#xD;
&#xD;
          -  Known active alcohol or substance abuse including cigarette/cigar smoking&#xD;
&#xD;
          -  Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia&#xD;
             (&lt;1,000/L), neutropenia (&lt;1,500/L), or thrombocytopenia (platelets &lt;100,000/L).&#xD;
&#xD;
          -  A history of Factor V deficiency or other coagulopathy defined by INR &gt;1.5, PTT&gt;40, PT&#xD;
             &gt;15.&#xD;
&#xD;
          -  Any coagulopathy or medical condition requiring long-term anticoagulant therapy(e.g.,&#xD;
             warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients&#xD;
             with an INR &gt;1.5.&#xD;
&#xD;
          -  Acute or chronic pancreatitis.&#xD;
&#xD;
          -  Symptomatic peptic ulcer disease.&#xD;
&#xD;
          -  Hyperlipidemia despite medical therapy (fasting LDL cholesterol &gt;130 mg/dl, treated or&#xD;
             untreated; and/or fasting triglycerides &gt; 200 mg/dl).&#xD;
&#xD;
          -  Receiving treatment for a medical condition requiring chronic use of systemic&#xD;
             steroids.&#xD;
&#xD;
          -  Symptomatic cholecystolithiasis.&#xD;
&#xD;
          -  Use of any investigational agents within 4 weeks of enrollment.&#xD;
&#xD;
          -  Admission to hospital for any reason in the 14 days prior to enrollment (signing&#xD;
             consent).&#xD;
&#xD;
          -  Presence of active proliferative diabetic retinopathy or macular edema&#xD;
&#xD;
          -  Any malignancy&#xD;
&#xD;
          -  Abnormal liver function &gt;1.5 x ULN&#xD;
&#xD;
          -  Abdominal aortic aneurysm&#xD;
&#xD;
          -  History of cerebro-vascular accident&#xD;
&#xD;
          -  Any patient with acute or subacute decompensation from diabetes&#xD;
&#xD;
          -  Any acute or chronic infectious condition that in the criteria of the investigator&#xD;
             would be a risk for the patient.&#xD;
&#xD;
          -  Subjects with hypoproteinemia, cachexia or terminal states&#xD;
&#xD;
          -  Subjects with history of anorexia/bulimia&#xD;
&#xD;
          -  Subjects with respiratory insufficiency&#xD;
&#xD;
          -  Subjects that are being treated with any medication that could interfere with the&#xD;
             outcome of the study such as: Sulfonylureas, Thiazolidinediones and glucagon like&#xD;
             peptide 1 (GLP-1) analogues (Exenatide, Byetta), Pramlintide (Amylin),&#xD;
             Dipeptidylpeptidase IV (DPP-IV) inhibitors (i.e. Sitagliptin, Januvia)&#xD;
&#xD;
          -  Any medical condition that, in the opinion of the investigator, will interfere with&#xD;
             thesafe completion of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Fuzhou General Hospital, Xiamen Univ</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>October 6, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fuzhou General Hospital</investigator_affiliation>
    <investigator_full_name>Jianming Tan</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>mesenchymal stem cells</keyword>
  <keyword>bone marrow mononeclear cells</keyword>
  <keyword>type 2 diabetes mellitus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01719640
org study id: MSC-MC-DM
nct id: NCT01719640
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Cell injury in human islets induced by non-immune mediated inflammation occur in vitro upon
      hyperglycemia in type 2 diabetes mellitus. Infusion of autologous bone marrow mononuclear
      cells (MCs) is an emerging therapeutic approach for DM, which showed promising outcomes with
      mild side effects. Infusion of MCs and autologous bone marrow mesenchymal stem cells in
      combination might exert enhanced repairing effects. We hypothesized that infusion of these
      two classes of cells might provide multiple signals for regeneration and improve recovery
      from inflammation-induced lesion. The effects might be maximized by intra-arterial pancreatic
      infusion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: macrovascular complications
time frame: 8 years
measure: microvascular complications
time frame: 8 years
measure: DPN
time frame: 8 years
description: diabetes peripheral neuropathy
measure: MI
time frame: 8 years
description: myocardial infarction
measure: angina
time frame: 8 years
description: angina
measure: stroke
time frame: 8 years
description: stroke
measure: amputation
time frame: 8 years
description: amputation
measure: DN
time frame: 8 years
description: diabetes nephropathy
measure: DRP
time frame: 8 years
description: diabetes retinopathy
measure: pro-DRP
time frame: 8 years
description: proliferative diabetes retinopathy
measure: C-peptide AUC
time frame: 1y
description: C-peptide area under the curve
measure: insulin AUC
time frame: 1y
description: insulin area under the curve
measure: HbA1c
time frame: 1y
description: glycated hemoglobin
measure: FBG
time frame: 1y
description: fasting hemoglucose
measure: insuline dose
time frame: 1y
description: exogenous insulin requirements
measure: fasting C-p
time frame: 1y
description: fasting c-peptide
measure: The incidence and severity of adverse events related to the stem cell infusion procedure
time frame: 8y
arm group label: MSC+MC
arm group type: Experimental
description: infusion of BMMSC+BMMNC and insulin injection
arm group label: MC
arm group type: Active Comparator
description: infusion of BMMNC and insulin injection
arm group label: Insulin
arm group type: Active Comparator
description: insulin injection
intervention type: Drug
intervention name: infusion of MSCs
description: infusion of MSCs
arm group label: MSC+MC
intervention type: Drug
intervention name: infusion MCs
description: infusion of MCs
arm group label: MC
arm group label: MSC+MC
intervention type: Drug
intervention name: insulin
description: intensive insulin care
arm group label: Insulin
arm group label: MC
arm group label: MSC+MC
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fuzhou General Hospital
investigator full name: Jianming Tan
investigator title: Professor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin