<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/NCT01681550</url>
  </required_header>
  <id_info>
    <org_study_id>8-Kamoi</org_study_id>
    <nct_id>NCT01681550</nct_id>
  </id_info>
  <brief_title>A Cohort Study of Incretin-based Therapy Combined With Insulin in Type 2 Diabetic Patients for 5 Years</brief_title>
  <official_title>Effect of Incretin-based Therapy Combined With Insulin on HbA1c, Hypoglycemia and Chronic Diabetic Complications in Type 2 Diabetic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nagaoka Red Cross Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nagaoka Red Cross Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The use of dipeptidyl-peptidase 4 (DPP-4) inhibitors and glucagon like peptide 1 (GLP1)&#xD;
      analogues for the treatment of diabetic mellitus (DM) type 2 is growing (1,2). Currently,&#xD;
      some of these agents have been approved in combination with insulin. The potential for&#xD;
      combined use with insulin has garnered increasing attention due to reduce side effects&#xD;
      associated with insulin therapy and improve glycemic control. Some investigators reported&#xD;
      that GLP-1 analogue combined with insulin reduces HbA1c and weight with low risk of&#xD;
      hypoglycemia and high treatment satisfaction (3). However, their duration of treatment was&#xD;
      short time with less than a mean of 3.0 years and the alterations of chronic diabetic&#xD;
      complications by combination with incretin-based and insulin therapies are not known.&#xD;
&#xD;
      We evaluated the long effects of adding incretin-based therapy (DPP-4 inhibitors or GLP-1&#xD;
      analogues) to insulin therapy on glycated hemoglobin (HbA1c) as glycemic control, body mass&#xD;
      index (BMI), blood pressure (BP), insulin dosage, frequency of hypoglycemia, and chronic&#xD;
      diabetic complications for 5 years-treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients were treated with diet, exercise, and/or oral conventional pharmacotherapy combined&#xD;
      with insulin. Oral conventional pharmacotherapy consisted of α-glycosidase inhibitors (α-GI),&#xD;
      sulfonylurea (SU), biguanide (BG), thiazolidinedione (TZD), or combinations of these agents.&#xD;
      Insulin therapy consisted of subcutaneous injections of long-acting insulin analogues prior&#xD;
      to sleep and bolus subcutaneous injections of rapid-acting insulin analogues in multiple&#xD;
      daily injections, or subcutaneous injections of mixed insulin analogues twice a day. In spite&#xD;
      of the treatments, when the physician in charge judged that their values of HbA1c were&#xD;
      inappropriate, the physician added the pharmacotherapy combined the insulin to incretin-based&#xD;
      therapy. 2.3.2. For ethical reasons, patients were treated with various anti-hypertensive,&#xD;
      anti-diabetic, anti-dyslipidemia and/or anti-hypercoagulation agents during the course of the&#xD;
      study by the patients' own doctors as a part of continuing standard medical care. As to the&#xD;
      drugs that have been used for the treatment of other disorders and its complication since the&#xD;
      time before the study, the content should not be changed during the study in principle unless&#xD;
      the complication is cured. If any new complication occurs during the study period, an&#xD;
      appropriate treatment is given by the judgment of investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">October 2018</completion_date>
  <primary_completion_date type="Anticipated">October 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>Duration varied between individual patients and was as the period of time after treatment with incretin-based therapy combined with insulin.</time_frame>
    <description>The cause of death was determined by attending doctor or was assessed by interviewing the family.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>Duration varied between individual patients and was as the period of time until after treatment with incretin-based therapy combined with insulin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>BMI was calculated from body weight and height for at baseline and every 3 to 6 months throughout the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>Participants were examined using the same methods reported previously (4). Briefly, BP was measured in the clinic and at home on waking in the morning at trough by the same methods included device, device validation, observer, number of measurements, conditions, posture and cuffs described previously (4). Namely, clinic BP (CBP) was measured once in each clinic visit. Home BP (HBP) was measured every day in the morning within 10 minutes after awakening in the sitting position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin dose</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemia</measure>
    <time_frame>Average time requires 5 yearsinsulin.</time_frame>
    <description>Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemia</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>Hypoglycemia and the number of time per day were assessed by medical examination owing to interview.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microvascular complications including renal anemia</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>They were assessment by the method mentioned above. As renal anemia, serum hemoglobin (Hb) was measured by cyanmet-hemoglobin method using commercial reagent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrovasular complications</measure>
    <time_frame>Average time requires 5 years</time_frame>
    <description>They were confirmed by medical history, including contents of treatment. New or worsened (recurrent) events were defined based on clinical manifestations and treatment throughout the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Incretin theapy combined with insulin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Incretin-based therapy</intervention_name>
    <arm_group_label>Incretin theapy combined with insulin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        After a detailed baseline examination, 500 Japanese subjects with type 2 diabetes were&#xD;
        followed up for all-cause mortality and morbidity. All participants visited our clinic&#xD;
        regularly. All patients were fully informed about the purposes and procedures for the study&#xD;
        and provided oral consent at enrolment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients participating in other clinical study. Other than the above, patients judged&#xD;
        inappropriate as the subjects of this study by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kyuzi Kamoi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nagaoka Red Cross Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kyuzi Kamoi, MD</last_name>
    <phone>+81-0258-28-3600</phone>
    <email>kkam-int@echigo.ne.jp</email>
  </overall_contact>
  <location>
    <facility>
      <name>Nagaoka Red Cross Hospital</name>
      <address>
        <city>Nagaoka</city>
        <state>Niigata</state>
        <zip>940-2085</zip>
        <country>Japan</country>
      </address>
    </facility>
    <contact>
      <last_name>Kyuzi Kamoi, MD</last_name>
      <phone>-81-0256-28-3600</phone>
      <email>kkam-int@echigo.ne.jp</email>
    </contact>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <results_reference>
    <citation>1. Rizos EC, Ntzani EE, Papanas N, Tsimihodimos V, Mitrogianni Z, Maltezos E, Elisaf MS. Combination therapies of DPP4 Inhibitors and GLP1 analogues with insulin in type 2 diabetic patients: A systematic review. Curr Vasc Pharmacol. 2012 Jun 22. [Epub ahead of print] 2. Jendle J, Martin SA, Milicevic Z. Insulin and GLP-1 analog combinations in type 2 diabetes mellitus: a critical review. Expert Opin Investig Drugs. 2012 Jul 16. [Epub ahead of print] 3. Lind M, Jendle J, Torffvit O, Lager I. Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction. Prim Care Diabetes. 2012; 6: 41-46. 4. Kamoi K, Miyakoshi M, Soda S, Kaneko S, Nakagawa O. Usefulness of home blood pressure measurement in the morning in type 2 diabetic patients. Diabetes Care 2002; 25: 2218-2223.</citation>
  </results_reference>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 2, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>September 8, 2012</last_update_submitted>
  <last_update_submitted_qc>September 8, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 11, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nagaoka Red Cross Hospital</investigator_affiliation>
    <investigator_full_name>Kyuzi Kamoi</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Incretins</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/NCT01681550
org study id: 8-Kamoi
nct id: NCT01681550
lead sponsor: 
has dmc: Yes
The use of dipeptidyl-peptidase 4 (DPP-4) inhibitors and glucagon like peptide 1 (GLP1)
      analogues for the treatment of diabetic mellitus (DM) type 2 is growing (1,2). Currently,
      some of these agents have been approved in combination with insulin. The potential for
      combined use with insulin has garnered increasing attention due to reduce side effects
      associated with insulin therapy and improve glycemic control. Some investigators reported
      that GLP-1 analogue combined with insulin reduces HbA1c and weight with low risk of
      hypoglycemia and high treatment satisfaction (3). However, their duration of treatment was
      short time with less than a mean of 3.0 years and the alterations of chronic diabetic
      complications by combination with incretin-based and insulin therapies are not known.

      We evaluated the long effects of adding incretin-based therapy (DPP-4 inhibitors or GLP-1
      analogues) to insulin therapy on glycated hemoglobin (HbA1c) as glycemic control, body mass
      index (BMI), blood pressure (BP), insulin dosage, frequency of hypoglycemia, and chronic
      diabetic complications for 5 years-treatments.
Patients were treated with diet, exercise, and/or oral conventional pharmacotherapy combined
      with insulin. Oral conventional pharmacotherapy consisted of α-glycosidase inhibitors (α-GI),
      sulfonylurea (SU), biguanide (BG), thiazolidinedione (TZD), or combinations of these agents.
      Insulin therapy consisted of subcutaneous injections of long-acting insulin analogues prior
      to sleep and bolus subcutaneous injections of rapid-acting insulin analogues in multiple
      daily injections, or subcutaneous injections of mixed insulin analogues twice a day. In spite
      of the treatments, when the physician in charge judged that their values of HbA1c were
      inappropriate, the physician added the pharmacotherapy combined the insulin to incretin-based
      therapy. 2.3.2. For ethical reasons, patients were treated with various anti-hypertensive,
      anti-diabetic, anti-dyslipidemia and/or anti-hypercoagulation agents during the course of the
      study by the patients' own doctors as a part of continuing standard medical care. As to the
      drugs that have been used for the treatment of other disorders and its complication since the
      time before the study, the content should not be changed during the study in principle unless
      the complication is cured. If any new complication occurs during the study period, an
      appropriate treatment is given by the judgment of investigator.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Death
time frame: Duration varied between individual patients and was as the period of time after treatment with incretin-based therapy combined with insulin.
description: The cause of death was determined by attending doctor or was assessed by interviewing the family.
measure: HbA1c
time frame: Average time requires 5 years
description: Duration varied between individual patients and was as the period of time until after treatment with incretin-based therapy combined with insulin.
measure: BMI
time frame: Average time requires 5 years
description: BMI was calculated from body weight and height for at baseline and every 3 to 6 months throughout the study.
measure: Blood pressure
time frame: Average time requires 5 years
description: Participants were examined using the same methods reported previously (4). Briefly, BP was measured in the clinic and at home on waking in the morning at trough by the same methods included device, device validation, observer, number of measurements, conditions, posture and cuffs described previously (4). Namely, clinic BP (CBP) was measured once in each clinic visit. Home BP (HBP) was measured every day in the morning within 10 minutes after awakening in the sitting position.
measure: Insulin dose
time frame: Average time requires 5 years
description: Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.
measure: Hypoglycemia
time frame: Average time requires 5 yearsinsulin.
description: Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.
measure: Hypoglycemia
time frame: Average time requires 5 years
description: Hypoglycemia and the number of time per day were assessed by medical examination owing to interview.
measure: Microvascular complications including renal anemia
time frame: Average time requires 5 years
description: They were assessment by the method mentioned above. As renal anemia, serum hemoglobin (Hb) was measured by cyanmet-hemoglobin method using commercial reagent.
measure: Macrovasular complications
time frame: Average time requires 5 years
description: They were confirmed by medical history, including contents of treatment. New or worsened (recurrent) events were defined based on clinical manifestations and treatment throughout the study.
arm group label: Incretin theapy combined with insulin
arm group type: Other
intervention type: Drug
intervention name: Incretin-based therapy
arm group label: Incretin theapy combined with insulin
criteria: 
gender: All
minimum age: 20 Years
maximum age: 95 Years
healthy volunteers: No
last name: Kyuzi Kamoi, MD
role: Principal Investigator
affiliation: Nagaoka Red Cross Hospital
last name: Kyuzi Kamoi, MD
phone: +81-0258-28-3600
email: kkam-int@echigo.ne.jp
facility: 
contact: 
country: Japan
citation: 1. Rizos EC, Ntzani EE, Papanas N, Tsimihodimos V, Mitrogianni Z, Maltezos E, Elisaf MS. Combination therapies of DPP4 Inhibitors and GLP1 analogues with insulin in type 2 diabetic patients: A systematic review. Curr Vasc Pharmacol. 2012 Jun 22. [Epub ahead of print] 2. Jendle J, Martin SA, Milicevic Z. Insulin and GLP-1 analog combinations in type 2 diabetes mellitus: a critical review. Expert Opin Investig Drugs. 2012 Jul 16. [Epub ahead of print] 3. Lind M, Jendle J, Torffvit O, Lager I. Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction. Prim Care Diabetes. 2012; 6: 41-46. 4. Kamoi K, Miyakoshi M, Soda S, Kaneko S, Nakagawa O. Usefulness of home blood pressure measurement in the morning in type 2 diabetic patients. Diabetes Care 2002; 25: 2218-2223.
responsible party type: Principal Investigator
investigator affiliation: Nagaoka Red Cross Hospital
investigator full name: Kyuzi Kamoi
investigator title: MD
mesh term: Diabetes Mellitus, Type 2
mesh term: Incretins