<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/NCT03801057</url>
  </required_header>
  <id_info>
    <org_study_id>2018/1825</org_study_id>
    <nct_id>NCT03801057</nct_id>
  </id_info>
  <brief_title>Marine Protein Hydrolysate as Dietary Supplement in Irritable Bowel Syndrome</brief_title>
  <acronym>MPH_IBS</acronym>
  <official_title>The Effect of a Marine Protein Hydrolysate Supplement on Inflammatory Markers, Microbiota Composition and Symptoms in Patients With Irritable Bowel Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Møre og Romsdal HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Haukeland University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Bergen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helse Møre og Romsdal HF</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>
      The use of natural bioactive products for prevention and treatment of a wide spectrum of&#xD;
      conditions, including gastrointestinal disorders and conditions is well known. Based on&#xD;
      current evidences, the scientific validity of such products is limited. However, there is&#xD;
      sufficient preliminary data to indicate that bioactive compounds may be novel for potentially&#xD;
      clinical use, thus further clinical trials investigating effect are needed. This trial is&#xD;
      meant to evaluate the effect of an marine protein hydrolysate (MPH) supplement on composition&#xD;
      of microbiota, inflammatory markers and symptom severity in people diagnosed with irritable&#xD;
      bowel syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Previous studies performed in rodents have found that hydrolyzed proteins from fish alters&#xD;
      the lipid and cholesterol metabolism, reduce plasma cholesterol and triglyceride levels and&#xD;
      alters the fatty acid composition in liver and adipose tissue. Previous studies in humans&#xD;
      have found marine peptides to have both antihypertensive and antioxidant effects. It is also&#xD;
      suggested that fish protein hydrolysates may have an immunomodulating effect with beneficial&#xD;
      properties in the intestine, and may prevent NSAID-induced injuries, change permeability in&#xD;
      the gut and possibly prevent injurious conditions in the gut.&#xD;
&#xD;
      The evidence and knowledge are limited on the interaction between diet, gut microbiota and&#xD;
      the influence of specific nutrients, as well as the impact of different sources of proteins&#xD;
      on inflammation markers, gut microbiota and symptom severity in patients with irritable bowel&#xD;
      syndrome (IBS). Different dietary sources of protein affect the diversity and composition of&#xD;
      the human gut microbiota in different degree, demonstrated by a distinct gut bacteria profile&#xD;
      observed between omnivores and vegetarians.The specific effect of marine peptides on human&#xD;
      gut microbiota composition is as far as the investigators know, previously not investigated.&#xD;
      Interestingly, novel results indicate that the presence of fish proteins in the diet have&#xD;
      impact on both composition and activity of the gut microbiome, influencing the human&#xD;
      microbiota composition.&#xD;
&#xD;
      The many benefits of expanding the utilization of marine products, the previous assumed&#xD;
      beneficial intestinal effect and the increased interest in gut health and microbiota, as well&#xD;
      as a great need for novel dietary treatment strategies for patients with irritable bowel&#xD;
      syndrome (IBS) make this study warrant.&#xD;
&#xD;
      Aim with this trial is to evaluate the effect of an marine protein hydrolysate (MPH)&#xD;
      supplement on composition of microbiota, inflammatory markers and symptom severity in human&#xD;
      subjects diagnosed with IBS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Actual">April 21, 2019</completion_date>
  <primary_completion_date type="Actual">March 21, 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>A parallel group randomized, controlled clinical trial for six weeks</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The provider of the dietary supplement deliver the supplement prepared and packed in equal bags (active/placebo) that we hand out to the participants in an randomized order.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>IBS-SSS</measure>
    <time_frame>Before (baseline) and after intervention (6 weeks later).</time_frame>
    <description>A decrease of 50 points or more in IBS-SSS, which is a clinically meaningful improvement.The IBS-SSS is a 5-question survey that asks the severity of abdominal pain, frequency of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits, and interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Scores on the IBS-SSS can range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (&gt;300) IBS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>SF-NDI_HRQOL</measure>
    <time_frame>Before (baseline) and after intervention (6 weeks later).</time_frame>
    <description>The Short Form (SF) Nepean Dyspepsia Index is a 10-item questionnaire with 5 sub-scales each examining the influence of dyspepsia on domains of health in patients, namely tension/anxiety, interference with daily activities, disruption to regular eating/drinking, knowledge towards/control over disease symptoms and interference with work/study, with each sub-scale containing two items . Each item is measured by a 5-point Likert scale ranging from 0 (not at all or not applicable), 1 (a little), 2 (moderately), 3 (quite a lot) to 4 (extremely). Individual items in each sub-scale are aggregated to obtain a score range from 0 (lowest HRQoL score) to 100 (highest HRQoL score) as per the developers' original calculation formula. A total, overall SF-NDI total score is obtained using the mean of 5 subscale scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal Calprotectin</measure>
    <time_frame>Before (baseline) and after intervention (6 weeks later).</time_frame>
    <description>Calprotectin is a protein found in several human fluids. When detected in the stool, calprotectin has a direct relationship (consequence of neutrophil degranulation) to inflammation in the bowel.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Inflammatory markers in blood</measure>
    <time_frame>Before (baseline) and after intervention (6 weeks later).</time_frame>
    <description>Zonulin, iFABP (intestinal fatty acid binding protein), LBP (lipopolysaccharide binding protein), IL-4, 6, 8, 10, TNF-α and INF-γ are markers of bowel mucosal damage.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>MPH_active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily intake at breakfast of supplementary marine protein hydrolysate (MPH). Random sequence of arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MPH_placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily intake at breakfast of supplementary placebo. Random sequence of arms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>MPH_active</intervention_name>
    <description>One daily intake at breakfast of supplementary marine protein hydrolysate (MPH), a dosage of 2400 mg, duration 6 weeks. The form is powder, flavored with lemon, and to be mixed with 100 ml water. Random sequence of arms.</description>
    <arm_group_label>MPH_active</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>MPH_placebo</intervention_name>
    <description>One daily intake at breakfast of supplementary placebo, a dosage of 2400 mg, duration 6 weeks. The form is powder, flavored with lemon, and to be mixed with 100 ml water.</description>
    <arm_group_label>MPH_placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Body mass index (BMI) 18-30 kg/m2&#xD;
&#xD;
          -  Irritable Bowel Syndrome (IBS) diagnosis according to Rome IV criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Suspected allergies against fish or shellfish&#xD;
&#xD;
          -  Low or unstable blood pressure&#xD;
&#xD;
          -  Diabetes mellitus pharmacologically treated&#xD;
&#xD;
          -  Chronic diseases or therapies that are likely to interfere with the evaluation of&#xD;
             study results such as known inflammation&#xD;
&#xD;
          -  Acute infections (may be reconsidered for inclusion at a later time)&#xD;
&#xD;
          -  Substance misuse&#xD;
&#xD;
          -  Inability or unwillingness to comply with the requirements of study procedures&#xD;
&#xD;
          -  Individuals in the middle of testing different dietary strategies for the treatment of&#xD;
             IBS (such as the low-FODMAP diet) and/or not willing to/able to maintain a stable diet&#xD;
             throughout the study period&#xD;
&#xD;
          -  Use of pro- or prebiotic supplements&#xD;
&#xD;
          -  Use of antibiotic treatment for the last 4 weeks&#xD;
&#xD;
          -  Immunocompromised patient defined as taking immuno-suppressive medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dag Arne Lihaug Hoff, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Helse Møre og Romsdal Hospital Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Haukeland University Hospital</name>
      <address>
        <city>Bergen</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ålesund Hospital, Helse Møre og Romsdal HF</name>
      <address>
        <city>Ålesund</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <results_reference>
    <citation>Dale HF, Jensen C, Hausken T, Valeur J, Hoff DAL, Lied GA. Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome. Nutrients. 2019 Jul 17;11(7):1635. doi: 10.3390/nu11071635.</citation>
    <PMID>31319590</PMID>
  </results_reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>August 12, 2019</last_update_submitted>
  <last_update_submitted_qc>August 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dietary Supplements</keyword>
  <keyword>Fish Proteins</keyword>
  <keyword>Protein Hydrolysates</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03801057
org study id: 2018/1825
nct id: NCT03801057
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The use of natural bioactive products for prevention and treatment of a wide spectrum of
      conditions, including gastrointestinal disorders and conditions is well known. Based on
      current evidences, the scientific validity of such products is limited. However, there is
      sufficient preliminary data to indicate that bioactive compounds may be novel for potentially
      clinical use, thus further clinical trials investigating effect are needed. This trial is
      meant to evaluate the effect of an marine protein hydrolysate (MPH) supplement on composition
      of microbiota, inflammatory markers and symptom severity in people diagnosed with irritable
      bowel syndrome.
Previous studies performed in rodents have found that hydrolyzed proteins from fish alters
      the lipid and cholesterol metabolism, reduce plasma cholesterol and triglyceride levels and
      alters the fatty acid composition in liver and adipose tissue. Previous studies in humans
      have found marine peptides to have both antihypertensive and antioxidant effects. It is also
      suggested that fish protein hydrolysates may have an immunomodulating effect with beneficial
      properties in the intestine, and may prevent NSAID-induced injuries, change permeability in
      the gut and possibly prevent injurious conditions in the gut.

      The evidence and knowledge are limited on the interaction between diet, gut microbiota and
      the influence of specific nutrients, as well as the impact of different sources of proteins
      on inflammation markers, gut microbiota and symptom severity in patients with irritable bowel
      syndrome (IBS). Different dietary sources of protein affect the diversity and composition of
      the human gut microbiota in different degree, demonstrated by a distinct gut bacteria profile
      observed between omnivores and vegetarians.The specific effect of marine peptides on human
      gut microbiota composition is as far as the investigators know, previously not investigated.
      Interestingly, novel results indicate that the presence of fish proteins in the diet have
      impact on both composition and activity of the gut microbiome, influencing the human
      microbiota composition.

      The many benefits of expanding the utilization of marine products, the previous assumed
      beneficial intestinal effect and the increased interest in gut health and microbiota, as well
      as a great need for novel dietary treatment strategies for patients with irritable bowel
      syndrome (IBS) make this study warrant.

      Aim with this trial is to evaluate the effect of an marine protein hydrolysate (MPH)
      supplement on composition of microbiota, inflammatory markers and symptom severity in human
      subjects diagnosed with IBS.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A parallel group randomized, controlled clinical trial for six weeks
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: The provider of the dietary supplement deliver the supplement prepared and packed in equal bags (active/placebo) that we hand out to the participants in an randomized order.
measure: IBS-SSS
time frame: Before (baseline) and after intervention (6 weeks later).
description: A decrease of 50 points or more in IBS-SSS, which is a clinically meaningful improvement.The IBS-SSS is a 5-question survey that asks the severity of abdominal pain, frequency of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits, and interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Scores on the IBS-SSS can range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS.
measure: SF-NDI_HRQOL
time frame: Before (baseline) and after intervention (6 weeks later).
description: The Short Form (SF) Nepean Dyspepsia Index is a 10-item questionnaire with 5 sub-scales each examining the influence of dyspepsia on domains of health in patients, namely tension/anxiety, interference with daily activities, disruption to regular eating/drinking, knowledge towards/control over disease symptoms and interference with work/study, with each sub-scale containing two items . Each item is measured by a 5-point Likert scale ranging from 0 (not at all or not applicable), 1 (a little), 2 (moderately), 3 (quite a lot) to 4 (extremely). Individual items in each sub-scale are aggregated to obtain a score range from 0 (lowest HRQoL score) to 100 (highest HRQoL score) as per the developers' original calculation formula. A total, overall SF-NDI total score is obtained using the mean of 5 subscale scores.
measure: Fecal Calprotectin
time frame: Before (baseline) and after intervention (6 weeks later).
description: Calprotectin is a protein found in several human fluids. When detected in the stool, calprotectin has a direct relationship (consequence of neutrophil degranulation) to inflammation in the bowel.
measure: Inflammatory markers in blood
time frame: Before (baseline) and after intervention (6 weeks later).
description: Zonulin, iFABP (intestinal fatty acid binding protein), LBP (lipopolysaccharide binding protein), IL-4, 6, 8, 10, TNF-α and INF-γ are markers of bowel mucosal damage.
arm group label: MPH_active
arm group type: Active Comparator
description: Daily intake at breakfast of supplementary marine protein hydrolysate (MPH). Random sequence of arms.
arm group label: MPH_placebo
arm group type: Placebo Comparator
description: Daily intake at breakfast of supplementary placebo. Random sequence of arms.
intervention type: Dietary Supplement
intervention name: MPH_active
description: One daily intake at breakfast of supplementary marine protein hydrolysate (MPH), a dosage of 2400 mg, duration 6 weeks. The form is powder, flavored with lemon, and to be mixed with 100 ml water. Random sequence of arms.
arm group label: MPH_active
intervention type: Dietary Supplement
intervention name: MPH_placebo
description: One daily intake at breakfast of supplementary placebo, a dosage of 2400 mg, duration 6 weeks. The form is powder, flavored with lemon, and to be mixed with 100 ml water.
arm group label: MPH_placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dag Arne Lihaug Hoff, MD, PhD
role: Study Director
affiliation: Helse Møre og Romsdal Hospital Trust
facility: 
facility: 
country: Norway
citation: Dale HF, Jensen C, Hausken T, Valeur J, Hoff DAL, Lied GA. Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome. Nutrients. 2019 Jul 17;11(7):1635. doi: 10.3390/nu11071635.
PMID: 31319590
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
sharing ipd: Undecided