<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/NCT03765125</url>
  </required_header>
  <id_info>
    <org_study_id>VERIPA17</org_study_id>
    <nct_id>NCT03765125</nct_id>
  </id_info>
  <brief_title>Dietary Collagen Peptides and Periodontal Inflammation</brief_title>
  <official_title>Dietary Intake of Collagen Peptides and Its Effects on Periodontal Inflammation - a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wuerzburg University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wuerzburg University Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is&#xD;
      designed to evaluate the impact of the regular consumption of collagen peptides on the&#xD;
      clinical signs of gingival and periodontal inflammation in a cohort of patients suffering&#xD;
      from periodontal disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The positive influence of the regular consumption of bioactive collagen peptides on&#xD;
      connective tissue and skin physiology has already been documented by several clinical trials.&#xD;
      Preliminary data of an observational clinical trial involving periodontitis patients suggest&#xD;
      that the adjunctive consumption of bio-active collagen peptides may also improve the outcome&#xD;
      of established periodontitis therapy comprising the professional mechanical removal of&#xD;
      disease-associated bacterial biofilms from exposed root surfaces.&#xD;
&#xD;
      This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is&#xD;
      designed to evaluate the impact of the regular, 3-month consumption of collagen peptides on&#xD;
      clinical and microbiological parameter of periodontal health in a cohort of periodontal&#xD;
      recall patients with the following endpoints:&#xD;
&#xD;
      Primary Endpoint:&#xD;
&#xD;
      Change in the percentage of periodontal pockets being positive for bleeding on probing (BoP)&#xD;
      after the consumption of the collagen peptides in comparison to the consumption of a placebo&#xD;
      product&#xD;
&#xD;
      Secondary Endpoints:&#xD;
&#xD;
        1. changes in probing pocket depth (PPD)&#xD;
&#xD;
        2. changes in clinical attachment level (CAL)&#xD;
&#xD;
        3. changes in the periodontal inflammatory load as assessed by the calculation of the&#xD;
           periodontal inflamed surface area (PISA) index&#xD;
&#xD;
        4. changes in Gingival Index (GI) scores&#xD;
&#xD;
        5. changes in Plaque Control Record (PCR) scores&#xD;
&#xD;
        6. changes in Plaque Index scores&#xD;
&#xD;
        7. changes in the composition of the sulcular/pocket microbiota&#xD;
&#xD;
        8. changes in the composition of the intestinal microbiota&#xD;
&#xD;
      Examiner calibration is performed before the onset of the trial and is repeated in 8 weeks&#xD;
      intervals throughout the trial.&#xD;
&#xD;
      Sample Size Calculation As this is the first controlled clinical trial evaluating the impact&#xD;
      of collagen peptide consumption on the extent of periodontal inflammation, sample size&#xD;
      calculation is based on substitute data from preceding studies demonstrating an increase in&#xD;
      tissue healing by up to 30%.&#xD;
&#xD;
      With a given difference of 30% reduction in the number of bleeding periodontal pockets (BoP)&#xD;
      and an assumed standard deviation of 30% , sample size calculation resulted in a minimum of&#xD;
      19 subjects per group in order to be able to statistically verify differences with a power of&#xD;
      80%, and p&lt;0.05.&#xD;
&#xD;
      Chi-square-test with maximum likelihood method will be used for the analysis of categorical&#xD;
      variables, Mann-Whitney U-test will be used for the analysis of independent samples, and&#xD;
      Wilcoxon signed rank test for the analysis of paired samples. The level of significance will&#xD;
      be set to p≤0.05.&#xD;
&#xD;
      Study patients will be recruited from periodontitis patients seeking routine periodontal&#xD;
      maintenance care comprising professional mechanical plaque removal (PMPR) at the Dept. of&#xD;
      Periodontology of the University Hospital Wuerzburg.&#xD;
&#xD;
      At baseline prior to the performance of PMPR all above-mentioned study parameters will be&#xD;
      recorded. Subsequently the study participants will be randomly assigned to the experimental&#xD;
      groups (test/placebo) and a supply of the assigned product (test/placebo) will be given to&#xD;
      them with the instruction to consume it 1 x daily for the 3-month duration of the trial.&#xD;
&#xD;
      At 2 months (visit 2) and at 3 months (end of study) after the baseline examination all&#xD;
      clinical and microbiological parameters will be reassessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Actual">August 31, 2019</completion_date>
  <primary_completion_date type="Actual">August 26, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>randomized, double-blind, placebo-controlled 2-arm, parallel group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>test and placebo powder contained in coded blister packages of identical shape and colour Handing out of the assigned powder by a study nurse not involved in the clinical examination and data collection</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of periodontal sites being positive for bleeding on probing (BoP)</measure>
    <time_frame>90 days</time_frame>
    <description>Bleeding on probing will be recorded at 6 sites per tooth after gentle probing of the periodontal sulcus/pocket.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>clinical attachment level (CAL)</measure>
    <time_frame>90 days</time_frame>
    <description>clinical attachment level will be assessed using a manual periodontal probe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pocket probing depth (PPD)</measure>
    <time_frame>90 days</time_frame>
    <description>pocket depth will be assessed using a manual periodontal probe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>periodontal inflamed surface area (PISA)</measure>
    <time_frame>90 days</time_frame>
    <description>PISA values will be calculated using the recorded BoP, CAL and PPD data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>modified Gingival Index</measure>
    <time_frame>90 days</time_frame>
    <description>The modified Gingival Index will be recorded from the buccal aspect of all teeth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plaque Control Record</measure>
    <time_frame>90 days</time_frame>
    <description>The extension of plaque along the gingival margin will be assessed from the mesial, distal, buccal and oral aspects of all teeth using a standard periodontal probe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plaque Index</measure>
    <time_frame>90 days</time_frame>
    <description>The Plaque Index will be recorded from the vestibular aspects of the teeth 16, 21, 24, 36, 41, 44</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composition of the oral microbiota</measure>
    <time_frame>90 days</time_frame>
    <description>Subgingival plaque samples will be collected by paper points from the 4 deepest periodontal pockets of each patient and subsequently analysed by whole genome sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composition of the intestinal microbiota</measure>
    <time_frame>90 days</time_frame>
    <description>Stool samples will be collected from each study participant and subsequently analysed by whole genome sequencing</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Gingivitis</condition>
  <arm_group>
    <arm_group_label>collagen peptide test</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 x daily consumption of 1 blister package of the collagen-peptide test powder dissolved in water over a period of 90 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>collagen peptide placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1y daily consumption of 1 blister package of the placebo powder dissolved in water over a period of 90 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>collagen peptide test</intervention_name>
    <description>Collagen peptides from bovine skin with an average molecular weight of approx. 2,000 g/mol. Average particle size is about 150 μm.</description>
    <arm_group_label>collagen peptide test</arm_group_label>
    <other_name>collagen peptide placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>collagen peptide placebo</intervention_name>
    <description>collagen peptide placebo</description>
    <arm_group_label>collagen peptide placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  number of teeth ≥ 10&#xD;
&#xD;
          -  age ≥ 35 ≤ 70 years&#xD;
&#xD;
          -  body mass index (BMI) ≥ 24 ≤ 30&#xD;
&#xD;
          -  history of periodontal disease and inclusion in a regular scheme of supportive&#xD;
             periodontal therapy (regularly repeated subgingival biofilm removal 2-4 x/year)&#xD;
&#xD;
          -  presence of mild to moderate gingivitis (Gingiva Index &gt; category GI 0 ≤ category GI&#xD;
             2) at a minimum of 3 teeth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  manifestation of inflammatory oral mucosal diseases other than gingivitis&#xD;
&#xD;
          -  xerostomia (salivary flow ≤ 0.1 ml/minute)&#xD;
&#xD;
          -  inability for regular oral home care&#xD;
&#xD;
          -  inability to follow the study protocol due to intellectual or physical handicaps&#xD;
&#xD;
          -  history of malignancy, radiotherapy, or chemotherapy for malignancy in the past 5&#xD;
             years&#xD;
&#xD;
          -  current pregnancy&#xD;
&#xD;
          -  acute infections as HIV&#xD;
&#xD;
          -  existence of metabolic bone disease&#xD;
&#xD;
          -  smoking status of more than 10 cigarettes/day&#xD;
&#xD;
          -  use of antibiotics and/or anti-inflammatory medication within 4 weeks prior to&#xD;
             screening.&#xD;
&#xD;
          -  active orthodontic therapy&#xD;
&#xD;
          -  diabetes mellitus type I and II&#xD;
&#xD;
          -  regular consumption of medications interfering with gingival inflammation (e.g.&#xD;
             cortisol)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yvonne Jockel-Schneider, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wuerzburg University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dept. of Periodontology, University Hospital Wuerzburg</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Section of Periodontology</name>
      <address>
        <city>Wuerzburg</city>
        <zip>D-97070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>June 1, 2022</last_update_submitted>
  <last_update_submitted_qc>June 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>gingivitis</keyword>
  <keyword>collagen peptide</keyword>
  <keyword>plaque</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gingivitis</mesh_term>
    <mesh_term>Inflammation</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/NCT03765125
org study id: VERIPA17
nct id: NCT03765125
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is
      designed to evaluate the impact of the regular consumption of collagen peptides on the
      clinical signs of gingival and periodontal inflammation in a cohort of patients suffering
      from periodontal disease.
The positive influence of the regular consumption of bioactive collagen peptides on
      connective tissue and skin physiology has already been documented by several clinical trials.
      Preliminary data of an observational clinical trial involving periodontitis patients suggest
      that the adjunctive consumption of bio-active collagen peptides may also improve the outcome
      of established periodontitis therapy comprising the professional mechanical removal of
      disease-associated bacterial biofilms from exposed root surfaces.

      This randomized, double-blind, placebo-controlled 2-arm, parallel group clinical trial is
      designed to evaluate the impact of the regular, 3-month consumption of collagen peptides on
      clinical and microbiological parameter of periodontal health in a cohort of periodontal
      recall patients with the following endpoints:

      Primary Endpoint:

      Change in the percentage of periodontal pockets being positive for bleeding on probing (BoP)
      after the consumption of the collagen peptides in comparison to the consumption of a placebo
      product

      Secondary Endpoints:

        1. changes in probing pocket depth (PPD)

        2. changes in clinical attachment level (CAL)

        3. changes in the periodontal inflammatory load as assessed by the calculation of the
           periodontal inflamed surface area (PISA) index

        4. changes in Gingival Index (GI) scores

        5. changes in Plaque Control Record (PCR) scores

        6. changes in Plaque Index scores

        7. changes in the composition of the sulcular/pocket microbiota

        8. changes in the composition of the intestinal microbiota

      Examiner calibration is performed before the onset of the trial and is repeated in 8 weeks
      intervals throughout the trial.

      Sample Size Calculation As this is the first controlled clinical trial evaluating the impact
      of collagen peptide consumption on the extent of periodontal inflammation, sample size
      calculation is based on substitute data from preceding studies demonstrating an increase in
      tissue healing by up to 30%.

      With a given difference of 30% reduction in the number of bleeding periodontal pockets (BoP)
      and an assumed standard deviation of 30% , sample size calculation resulted in a minimum of
      19 subjects per group in order to be able to statistically verify differences with a power of
      80%, and p<0.05.

      Chi-square-test with maximum likelihood method will be used for the analysis of categorical
      variables, Mann-Whitney U-test will be used for the analysis of independent samples, and
      Wilcoxon signed rank test for the analysis of paired samples. The level of significance will
      be set to p≤0.05.

      Study patients will be recruited from periodontitis patients seeking routine periodontal
      maintenance care comprising professional mechanical plaque removal (PMPR) at the Dept. of
      Periodontology of the University Hospital Wuerzburg.

      At baseline prior to the performance of PMPR all above-mentioned study parameters will be
      recorded. Subsequently the study participants will be randomly assigned to the experimental
      groups (test/placebo) and a supply of the assigned product (test/placebo) will be given to
      them with the instruction to consume it 1 x daily for the 3-month duration of the trial.

      At 2 months (visit 2) and at 3 months (end of study) after the baseline examination all
      clinical and microbiological parameters will be reassessed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomized, double-blind, placebo-controlled 2-arm, parallel group
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: test and placebo powder contained in coded blister packages of identical shape and colour Handing out of the assigned powder by a study nurse not involved in the clinical examination and data collection
measure: Percentage of periodontal sites being positive for bleeding on probing (BoP)
time frame: 90 days
description: Bleeding on probing will be recorded at 6 sites per tooth after gentle probing of the periodontal sulcus/pocket.
measure: clinical attachment level (CAL)
time frame: 90 days
description: clinical attachment level will be assessed using a manual periodontal probe
measure: pocket probing depth (PPD)
time frame: 90 days
description: pocket depth will be assessed using a manual periodontal probe
measure: periodontal inflamed surface area (PISA)
time frame: 90 days
description: PISA values will be calculated using the recorded BoP, CAL and PPD data
measure: modified Gingival Index
time frame: 90 days
description: The modified Gingival Index will be recorded from the buccal aspect of all teeth
measure: Plaque Control Record
time frame: 90 days
description: The extension of plaque along the gingival margin will be assessed from the mesial, distal, buccal and oral aspects of all teeth using a standard periodontal probe.
measure: Plaque Index
time frame: 90 days
description: The Plaque Index will be recorded from the vestibular aspects of the teeth 16, 21, 24, 36, 41, 44
measure: Composition of the oral microbiota
time frame: 90 days
description: Subgingival plaque samples will be collected by paper points from the 4 deepest periodontal pockets of each patient and subsequently analysed by whole genome sequencing
measure: Composition of the intestinal microbiota
time frame: 90 days
description: Stool samples will be collected from each study participant and subsequently analysed by whole genome sequencing
arm group label: collagen peptide test
arm group type: Experimental
description: 1 x daily consumption of 1 blister package of the collagen-peptide test powder dissolved in water over a period of 90 days
arm group label: collagen peptide placebo
arm group type: Placebo Comparator
description: 1y daily consumption of 1 blister package of the placebo powder dissolved in water over a period of 90 days
intervention type: Dietary Supplement
intervention name: collagen peptide test
description: Collagen peptides from bovine skin with an average molecular weight of approx. 2,000 g/mol. Average particle size is about 150 μm.
arm group label: collagen peptide test
other name: collagen peptide placebo
intervention type: Dietary Supplement
intervention name: collagen peptide placebo
description: collagen peptide placebo
arm group label: collagen peptide placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yvonne Jockel-Schneider, Dr.
role: Principal Investigator
affiliation: Wuerzburg University Hospital
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Gingivitis
mesh term: Inflammation
sharing ipd: No