<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/NCT02196350</url>
  </required_header>
  <id_info>
    <org_study_id>P9607</org_study_id>
    <nct_id>NCT02196350</nct_id>
  </id_info>
  <brief_title>P4 Approach in Diabetes Type 2</brief_title>
  <acronym>P4P-Hillegom</acronym>
  <official_title>The Impact of the P4 Approach, Preventive, Predictive, Personalized and Participatory in Newly Diagnosed Type 2 Diabetics in Hillegom</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>W.J. Pasman</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TNO</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to assess the impact of the P4 approach on established markers of glucose&#xD;
      metabolism in type 2 diabetics.&#xD;
&#xD;
      Secondary objectives are examination of the changes in physical characteristics, quality of&#xD;
      life and the indices for beta cell function, hepatic insulin resistance and muscle insulin&#xD;
      resistance .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be a proof-of-principle exploratory study. Subjects in the P4 program will&#xD;
      receive a personalized diagnosis and treatment. After investigation of the status of the&#xD;
      different organs involved in diabetes (liver, muscle, pancreas), subjects in the P4 group are&#xD;
      divided into 3 subgroups. Each subgroup receives a personalized lifestyle advice. This&#xD;
      lifestyle advice may comprise different interventions, i.e. very low calorie diet, low&#xD;
      calorie diet, strength training, endurance training. Dependent on the type of intervention,&#xD;
      these interventions will be supervised by a dietitian or physiotherapist.&#xD;
&#xD;
      All subjects will visit a central study center 5 times during the study and 3 times during&#xD;
      follow-up. During these visits physical measures will be taken and data will be collected by&#xD;
      the general practitioner assistant.&#xD;
&#xD;
      After the three month intervention period the subjects will return to usual care via the&#xD;
      general practitioner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">July 2019</primary_completion_date>
  <phase>N/A</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>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c levels</measure>
    <time_frame>In-study at week 0 (baseline) and 13 (end of study); follow-up after 6, 12 and 24 months</time_frame>
    <description>Changes in primary outcome measures will be determined by using a mixed model</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in 2h glucose levels</measure>
    <time_frame>In-study at week 0 (baseline) and 13;</time_frame>
    <description>2h glucose will be measured after Oral Glucose Tolerance Test (OGTT). Changes in primary outcome measures will be determined by using a mixed model</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in fasting blood glucose levels</measure>
    <time_frame>In-study at week 0 (baseline) and 13 (end of study); follow-up after 6, 12 and 24 months</time_frame>
    <description>After 8 hour fasting. Changes in primary outcome measures will be determined by using a mixed model.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>percentage of participants that reach normoglycemia</measure>
    <time_frame>end of study (after 13 weeks)</time_frame>
    <description>normoglycemia is determined by fasting blood glucose level of less than 6.1 mmol/L</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>body weight</measure>
    <time_frame>screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months</time_frame>
    <description>measured by the general practitioner assistant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>blood pressure</measure>
    <time_frame>screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months</time_frame>
    <description>measured by the general practitioner assistant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>waist circumference</measure>
    <time_frame>screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months</time_frame>
    <description>measured by general practitioner assistant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>body fat percentage</measure>
    <time_frame>screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months</time_frame>
    <description>measured by general practitioner assistant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change indices for muscle insulin resistance</measure>
    <time_frame>screening; in-study at week 0 and 13;</time_frame>
    <description>at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.&#xD;
Blood will be collected at the blood collection centre in Hillegom</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>health behaviour change</measure>
    <time_frame>in-study at week 0, 13; during follow-up at 6, 12 and 24 months</time_frame>
    <description>established by comparing baseline values with end of study values for food intake and physical activity as measured by a Lifestyle-questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in vitality as assessed with a vitality questionnaire (Vita-16)</measure>
    <time_frame>in-study at week 0, 13; during follow-up at 6, 12 and 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in subjective quality of life as assessed with RAND-36 questionnaire</measure>
    <time_frame>in-study at week 0, 13; during follow-up at 6, 12 and 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in indices for beta cell function</measure>
    <time_frame>screening; in-study at week 0 and 13;</time_frame>
    <description>at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.&#xD;
Blood will be collected at the blood collection centre in Hillegom</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in indices for hepatic insulin resistance</measure>
    <time_frame>screening; in-study at week 0 and 13;</time_frame>
    <description>at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.&#xD;
Blood will be collected at the blood collection centre in Hillegom</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Intervention A: Diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention A: One week of very low calorie diet, 12 weeks of low calorie diet; exercise according to the Dutch Norm for Healthy Behaviour (Nederlandse Norm Gezond Bewegen).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention B: Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention B: Combination of strength and endurance training, 3 x per week 60 minutes according to the Exercise Program Diabetes (Beweegprogramma Diabetes).&#xD;
Healthy isocaloric diet.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention C: Diet and Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention C: one week very low calorie diet, followed by 12 weeks healthy isocaloric diet.&#xD;
One week exercise according to the Dutch Norm for Healthy Behaviour (Nederlandse Norm Gezond Bewegen) followed by 12 weeks strength and endurance training (3 x per week 60 minutes) according to the Exercise Program Diabetes (Beweegprogramma Diabetes)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control - Historical data</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Historical data from the GPs Information System from 60 newly diagnosed type 2 diabetes patients in the last five years will be used as control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Intervention A: Diet</intervention_name>
    <description>subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice</description>
    <arm_group_label>Intervention A: Diet</arm_group_label>
    <other_name>very low calorie diet based on Modifast meal replacers.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Intervention B: Exercise</intervention_name>
    <description>subjects visit the physiotherapist three times weekly; subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice.</description>
    <arm_group_label>Intervention B: Exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Intervention C: Diet and Exercise</intervention_name>
    <description>subjects visit the physiotherapist three times weekly; subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice.</description>
    <arm_group_label>Intervention C: Diet and Exercise</arm_group_label>
    <other_name>very low calorie diet based on Modifast meal replacers.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy as assessed by the&#xD;
&#xD;
               -  health and lifestyle questionnaire, (P9607 F02; in Dutch)&#xD;
&#xD;
               -  physical examination&#xD;
&#xD;
               -  results of the pre-study laboratory tests&#xD;
&#xD;
          2. Age 30-80 years&#xD;
&#xD;
          3. Stable BMI 25-35 kg/m2&#xD;
&#xD;
          4. Diagnosis diabetes type 2 based upon:&#xD;
&#xD;
             Fasting glucose &gt;6.9 mmol/l on two different days or one measurement of non-fasting&#xD;
             glucose &gt;11.0 mmol/l in combination with symptoms of hyperglycemia&#xD;
&#xD;
          5. Duration of diabetes maximally 1 year&#xD;
&#xD;
          6. Informed consent signed;&#xD;
&#xD;
          7. Willing to comply with the study procedures during the study;&#xD;
&#xD;
          8. Appropriate veins for blood sampling/ cannula insertion according to the general&#xD;
             practitioner assistant (GPA);&#xD;
&#xD;
          9. Voluntary participation&#xD;
&#xD;
         10. Physically able to perform training activities&#xD;
&#xD;
         11. Willing to accept use of all nameless data, including publication, and the&#xD;
             confidential use and storage of all data for at least 15 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of insulin, corticosteroids (systemic), or beta-blockers in past month&#xD;
&#xD;
          2. Diabetes occurring after several attacks of pancreatitis known as pancreatic diabetes&#xD;
&#xD;
          3. Slow onset type 1 diabetes&#xD;
&#xD;
          4. Use of oral diabetes medication in past year&#xD;
&#xD;
          5. (Having a history of a) medical condition that might significantly affect the study&#xD;
             outcome as judged by the medical investigator and health and life style questionnaire.&#xD;
             This includes diabetes type 1, gastrointestinal dysfunction, diseases related to&#xD;
             inflammation or allergy, or a psychiatric disorder.&#xD;
&#xD;
          6. Hypertension: systolic blood pressure &gt;160 mmHg, diastolic blood pressure &gt;90 mmHg&#xD;
&#xD;
          7. Kidney problems based upon proteinuria and creatinine &gt;150 mmol/l&#xD;
&#xD;
          8. Insufficient beta cell function based on Disposition index &lt; 1.5 as determined during&#xD;
             the OGTT in study on day 01*&#xD;
&#xD;
          9. Physical activity higher than according to the Diabetes guidelines (moderate intensity&#xD;
             one hour a day, seven days a week (overweight adults))&#xD;
&#xD;
         10. Alcohol consumption &gt; 21 (women) - 28 (men) units/week&#xD;
&#xD;
         11. Reported unexplained weight loss or gain of &gt; 2 kg in the month prior to the pre-study&#xD;
             screening&#xD;
&#xD;
         12. Recent blood donation (&lt;1 month prior to the start of the study)&#xD;
&#xD;
         13. Not willing to give up blood donation during the study&#xD;
&#xD;
         14. Personnel of TNO and their partner&#xD;
&#xD;
         15. Not having a general practitioner&#xD;
&#xD;
         16. Not willing to accept information-transfer concerning participation in the study, or&#xD;
             information regarding his health, like laboratory results, findings at anamnesis or&#xD;
             physical examination and eventual adverse events to and from his general practitioner.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wilrike Pasman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Netherlands Organisation for Applied Scientific Research (TNO)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter van Dijken, Dr.</last_name>
    <role>Study Director</role>
    <affiliation>Netherlands Organisation for Applied Scientific Research (TNO)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Netherlands Organisation for Applied Scientific Research (TNO)</name>
      <address>
        <city>Zeist</city>
        <state>Utrecht</state>
        <zip>3704 HE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk Lommelaars</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2181 EK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartspraktijk C.C. Dekker</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2181 EN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartspraktijk Tubbergen</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2181 EN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk Sixlaan 9</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2182 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk J.G. van Dusseldorp</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2182 CA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk van der Kaaden</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2182 GP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk Elsbroek</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2182 LN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huisartsenpraktijk Mulders</name>
      <address>
        <city>Hillegom</city>
        <state>Zuid Holland</state>
        <zip>2182 VT</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>October 24, 2019</last_update_submitted>
  <last_update_submitted_qc>October 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>TNO</investigator_affiliation>
    <investigator_full_name>W.J. Pasman</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>personalized treatment</keyword>
  <keyword>prevention</keyword>
  <keyword>improved diagnosis</keyword>
  <!-- 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/NCT02196350
org study id: P9607
nct id: NCT02196350
lead sponsor: 
has dmc: No
The study aims to assess the impact of the P4 approach on established markers of glucose
      metabolism in type 2 diabetics.

      Secondary objectives are examination of the changes in physical characteristics, quality of
      life and the indices for beta cell function, hepatic insulin resistance and muscle insulin
      resistance .
This study will be a proof-of-principle exploratory study. Subjects in the P4 program will
      receive a personalized diagnosis and treatment. After investigation of the status of the
      different organs involved in diabetes (liver, muscle, pancreas), subjects in the P4 group are
      divided into 3 subgroups. Each subgroup receives a personalized lifestyle advice. This
      lifestyle advice may comprise different interventions, i.e. very low calorie diet, low
      calorie diet, strength training, endurance training. Dependent on the type of intervention,
      these interventions will be supervised by a dietitian or physiotherapist.

      All subjects will visit a central study center 5 times during the study and 3 times during
      follow-up. During these visits physical measures will be taken and data will be collected by
      the general practitioner assistant.

      After the three month intervention period the subjects will return to usual care via the
      general practitioner.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Change in HbA1c levels
time frame: In-study at week 0 (baseline) and 13 (end of study); follow-up after 6, 12 and 24 months
description: Changes in primary outcome measures will be determined by using a mixed model
measure: Change in 2h glucose levels
time frame: In-study at week 0 (baseline) and 13;
description: 2h glucose will be measured after Oral Glucose Tolerance Test (OGTT). Changes in primary outcome measures will be determined by using a mixed model
measure: Change in fasting blood glucose levels
time frame: In-study at week 0 (baseline) and 13 (end of study); follow-up after 6, 12 and 24 months
description: After 8 hour fasting. Changes in primary outcome measures will be determined by using a mixed model.
measure: percentage of participants that reach normoglycemia
time frame: end of study (after 13 weeks)
description: normoglycemia is determined by fasting blood glucose level of less than 6.1 mmol/L
measure: body weight
time frame: screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months
description: measured by the general practitioner assistant
measure: blood pressure
time frame: screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months
description: measured by the general practitioner assistant
measure: waist circumference
time frame: screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months
description: measured by general practitioner assistant
measure: body fat percentage
time frame: screening; in-study at week 0, 4, 8 and 13; during follow up after 6, 12 and 24 months
description: measured by general practitioner assistant
measure: change indices for muscle insulin resistance
time frame: screening; in-study at week 0 and 13;
description: at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.
Blood will be collected at the blood collection centre in Hillegom
measure: health behaviour change
time frame: in-study at week 0, 13; during follow-up at 6, 12 and 24 months
description: established by comparing baseline values with end of study values for food intake and physical activity as measured by a Lifestyle-questionnaire
measure: change in vitality as assessed with a vitality questionnaire (Vita-16)
time frame: in-study at week 0, 13; during follow-up at 6, 12 and 24 months
measure: change in subjective quality of life as assessed with RAND-36 questionnaire
time frame: in-study at week 0, 13; during follow-up at 6, 12 and 24 months
measure: change in indices for beta cell function
time frame: screening; in-study at week 0 and 13;
description: at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.
Blood will be collected at the blood collection centre in Hillegom
measure: change in indices for hepatic insulin resistance
time frame: screening; in-study at week 0 and 13;
description: at week 0 and 13 the indices will be calculated from Oral glucose tolerance test data.
Blood will be collected at the blood collection centre in Hillegom
arm group label: Intervention A: Diet
arm group type: Experimental
description: Intervention A: One week of very low calorie diet, 12 weeks of low calorie diet; exercise according to the Dutch Norm for Healthy Behaviour (Nederlandse Norm Gezond Bewegen).
arm group label: Intervention B: Exercise
arm group type: Experimental
description: Intervention B: Combination of strength and endurance training, 3 x per week 60 minutes according to the Exercise Program Diabetes (Beweegprogramma Diabetes).
Healthy isocaloric diet.
arm group label: Intervention C: Diet and Exercise
arm group type: Experimental
description: Intervention C: one week very low calorie diet, followed by 12 weeks healthy isocaloric diet.
One week exercise according to the Dutch Norm for Healthy Behaviour (Nederlandse Norm Gezond Bewegen) followed by 12 weeks strength and endurance training (3 x per week 60 minutes) according to the Exercise Program Diabetes (Beweegprogramma Diabetes)
arm group label: Control - Historical data
arm group type: No Intervention
description: Historical data from the GPs Information System from 60 newly diagnosed type 2 diabetes patients in the last five years will be used as control.
intervention type: Behavioral
intervention name: Intervention A: Diet
description: subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice
arm group label: Intervention A: Diet
other name: very low calorie diet based on Modifast meal replacers.
intervention type: Behavioral
intervention name: Intervention B: Exercise
description: subjects visit the physiotherapist three times weekly; subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice.
arm group label: Intervention B: Exercise
intervention type: Behavioral
intervention name: Intervention C: Diet and Exercise
description: subjects visit the physiotherapist three times weekly; subjects visit the dietitian at week 0, 1, 2, 6, 10 and 13 for dietary advice.
arm group label: Intervention C: Diet and Exercise
other name: very low calorie diet based on Modifast meal replacers.
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Wilrike Pasman, PhD
role: Principal Investigator
affiliation: Netherlands Organisation for Applied Scientific Research (TNO)
last name: Peter van Dijken, Dr.
role: Study Director
affiliation: Netherlands Organisation for Applied Scientific Research (TNO)
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor-Investigator
investigator affiliation: TNO
investigator full name: W.J. Pasman
investigator title: PhD