<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/NCT03236038</url>
  </required_header>
  <id_info>
    <org_study_id>2017536</org_study_id>
    <nct_id>NCT03236038</nct_id>
  </id_info>
  <brief_title>Prevalence of Exocrine Pancreatic Insufficiency in Patients With Decompensated Cirrhosis</brief_title>
  <acronym>(EPIIHC)</acronym>
  <official_title>Prevalence of Exocrine Pancreatic Insufficiency in Patients With Decompensated Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Corporacion Parc Tauli</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Corporacion Parc Tauli</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>
      Exocrine pancreatic insufficiency (EPI) is the inability of the pancreas to perform a normal&#xD;
      digestive function. The prevalence of IPE in patients with decompensated hepatic cirrhosis&#xD;
      (HC) is unknown and most published series are short, old and use a single diagnostic&#xD;
      technique with potential risk of false positives and negatives. Demonstrating IPE in a&#xD;
      patient with HC can change their vital prognosis with the indication of pancreatic enzymes&#xD;
      that can improve their nutritional status and help control their decompensations.&#xD;
&#xD;
      Objectives: To assess the prevalence of IPE in patients with decompensated CH. To establish&#xD;
      correlation between fecal elastase and 13C triolein breath test.&#xD;
&#xD;
      Methodology: Unicentric, transversal study that will be carried out during hospitalization.&#xD;
      Patients with HC who enter for decompensation and requiere hospitalization will be included&#xD;
      consecutively. Exclusion criteria will include prior diagnosis of IPE, suspicion of biliary&#xD;
      obstruction, more than 5 dep / d induced by laxatives or liquid stools.&#xD;
&#xD;
      The diagnosis of IPE will be made with the combination of two techniques (13C triolein breath&#xD;
      test and fecal elastase).&#xD;
&#xD;
      Demographic, epidemiological data, clinical data as well as anthropometric parameters will be&#xD;
      collected. A blood test will also be done to assess nutritional status and associated&#xD;
      deficits. A multivariate analysis will be performed to assess the predictive factors of IPE&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Exocrine pancreatic insufficiency (EPI) is defined as the inability of the pancreas to&#xD;
      perform a normal digestive function. Habitually, it occurs as a result of a severe reduction&#xD;
      in the secretion of pancreatic enzymes, although - less frequently - it may be due to the&#xD;
      inability of these enzymes to perform their function. Clinically, it has a very broad&#xD;
      spectrum of presentation with abdominal discomforts, malnutrition, chronic diarrhea and, in&#xD;
      severe cases, steatorrhea. It must be said, however, that it is not until the disease is very&#xD;
      evolved with a pancreatic function very deteriorated (more than 90%) that steatorrhea becomes&#xD;
      clinically evident. In addition, the onset of symptoms triggered by the intake of fats makes&#xD;
      these patients adapt their diet, often unconsciously, so it is not uncommon to find patients&#xD;
      with EPI and constipation.&#xD;
&#xD;
      To establish the diagnosis of IPE, different clinical tests are used. There are direct&#xD;
      methods or invasive (secretin stimulation test, secretin-cerulein Lundh test) and noninvasive&#xD;
      or indirect methods (coefficient of fat absorption, fecal elastase, fecal chymotrypsin&#xD;
      activity, the pancreoleuril test, test with paraaminobenzoic acid and marked triolein test)&#xD;
      are, in general, more accessible to the usual clinical practice.&#xD;
&#xD;
      Regarding etiology, the most frequent cause of EPI is chronic pancreatitis, an entity that is&#xD;
      closely linked to chronic alcohol consumption. On the one hand, it should be noted that&#xD;
      alcohol is a common etiologic factor to both pathogenesis of pancreatic and liver affections.&#xD;
      On the other hand, it is well known that the liver and pancreas have a close relationship&#xD;
      with regard to their anatomy and physiology. The pancreatic duct and the coledocus bind to&#xD;
      the level of the Vater papilla, so that their contents are mixed.&#xD;
&#xD;
      Patients with EPI have severe malnutrition, a factor which increases the morbidity and&#xD;
      mortality. Therefore, adequately replacing nutritional deficits by enzyme replacement therapy&#xD;
      contributes significantly to decrease the complications, the hospital stays and the&#xD;
      mortality. It could increase the quality of life of the patients. In addition, patients&#xD;
      suffering from liver cirrhosis have other complications arising from malnutrition, as ascites&#xD;
      that could be benefited from the improvement of the nutritional profile by enzyme replacement&#xD;
      therapy detected in case of EPI. That is why we believe that our study could contribute to&#xD;
      improving patient management with decompensated liver cirrhosis.&#xD;
&#xD;
      The objective of the study is to assess the prevalence of exocrine pancreatic insufficiency&#xD;
      EPI in patients with decompensated alcoholic liver cirrhosis.&#xD;
&#xD;
      This is an epidemiological, unicentral, cross-sectional study that will be carried out within&#xD;
      the hospital setting from October '17 to October'19.&#xD;
&#xD;
      Patients diagnosed with liver cirrrhosis and enter the hepatology unit for clinical&#xD;
      decompensation (sd hepatorenal, ascitic decompensation, hepatic encephalopathy,&#xD;
      gastrointestinal bleeding stable) will be included .&#xD;
&#xD;
      The investigators will collect demographic, epidemiology, analytic and clinical data.&#xD;
      Anthropometric parameters such as tricipital fold, weight and size, will also be measured,&#xD;
      which will allow the calculation of body mass index (BMI).&#xD;
&#xD;
      In order to diagnose the presence of IPE, the breath test with triolein marked with 13C&#xD;
      (Pancreo-Kit®) will be performed. The study consists of a delay of 8 hours (overnight) and&#xD;
      later obtaining a basal sample through exhalation of air in a tube. Subsequently, a substrate&#xD;
      (foods with marked triolein) will be administered to the patient and after 30 minutes, it&#xD;
      will have to exhale air in a tube every 30 minutes for a total of 6 hours, thus obtaining a&#xD;
      total of 13 samples.&#xD;
&#xD;
      Blood tests will also be performed on all patients to assess their nutritional status (Hg,&#xD;
      albumin, prealbumin, total proteins, cholesterol (HDL / LDL), bilirubin, prothrombin time,&#xD;
      triglycerides, liposoluble Vitamins A, D, E and K; Vitamins B1, B12; calcium, phosphorus and&#xD;
      magnesium), Hb glucose and collect a sample of solid stool isolated for the determination of&#xD;
      the fecal elastase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>2 Years</target_duration>
  <primary_outcome>
    <measure>Prevalence of exocrine pancreatic insufficiency in decompensated alcoholic cirrhosis</measure>
    <time_frame>This is a prevalence study. Outcome measure will be assessed during patient admision in the hospital. Data will be reported once the inclusion has been completed (2 years).</time_frame>
    <description>The diagnosis of EPI will be made through the combination of two diagnostic tests.&#xD;
The labeled triolein breath test will use criteria established by the manufacturer of the product (Pancreo-Kit®) Isomed pharma.&#xD;
Reference value: Normal: &gt; 29%; Pathological: &lt; 29% of the fat administered&#xD;
The fecal elastase test (Bioserv Diagnostics (BS-86-01 Elastase Pancreatic ELISA) distributed by Palex Medical.)&#xD;
A normal result will be considered: 200 to &gt; 500 μg / g&#xD;
Slight exocrine pancreatic insufficiency- Moderate: 100 - 200 μg / g&#xD;
Severe exocrine pancreatic insufficiency: &lt;100 μg / g&#xD;
In those cases where both results are negative, it will be considered that there is no EPI. In cases where both results are positive, the diagnosis of EPI will be performed. If the results are discordant, a Sobel test or feces quantification test will be performed.&#xD;
Coefficient of fat absorption; Pathological if elimination &gt; 7g of fat / day with a diet of 100g fat / day.</description>
  </primary_outcome>
  <enrollment type="Actual">125</enrollment>
  <condition>Exocrine Pancreatic Insufficiency</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Labeled triolein urea breath test</intervention_name>
    <description>The diagnosis of EPI will be made through the combination of two diagnostic tests.&#xD;
The labeled triolein breath test will use criteria established by the manufacturer of the product (Pancreo-Kit®) Isomed pharma.&#xD;
The fecal elastase test will be performed at our own center (Bioserv Diagnostics (BS-86-01 Elastase Pancreatic ELISA) distributed by Palex Medical.) In those cases where both results are negative, it will be considered that there is no EPI. In cases where both results are positive, the diagnosis of EPI will be performed. If the results are discordant, a Sobel test or feces quantification test will be performed.</description>
    <other_name>fecal elastase</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with decompensated liver cirrhosis and who are admitted to hospital for this&#xD;
        reason. Patients will be included prospectively and consecutively.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histological diagnosis of CH or by clinical, analytical, ecographic or&#xD;
             fibroscan criteria.&#xD;
&#xD;
          2. Patients with decompensated HC (ascites, hepatic hydrothorax, hepatorenal syndrome,&#xD;
             digestive bleeding due to portal hypertension or hepatic encephalopathy.&#xD;
&#xD;
          3. Signature of informed consent&#xD;
&#xD;
          4. Prevision of hospital admission for a minimum of 48 hours (for the correct completion&#xD;
             of the marked triolein test and the collection of samples for fecal elastase)&#xD;
&#xD;
          5. Age between 18 and 85 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous diagnosis of EPI&#xD;
&#xD;
          2. Suspected biliary tract obstruction&#xD;
&#xD;
          3. Need for high doses of laxative which makes it impossible to collect faecal samples&#xD;
             correctly (&gt; 5 dep / d secondary to laxatives)&#xD;
&#xD;
          4. Patients who, due to their clinical situation, are unable to collaborate in the&#xD;
             labeled triolein breath test&#xD;
&#xD;
          5. Patients with inability to use the oral route.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jordi Sánchez-Delgado, M.D; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Corporació Sanitària Parc Tauli</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parc Tauli Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>28208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <results_reference>
    <citation>Aoufi Rabih S, Garcia Agudo R, Legaz Huidobro ML, Ynfante Ferrus M, Gonzalez Carro P, Perez Roldan F, Ruiz Carrillo F, Tenias Burillo JM. Exocrine pancreatic insufficiency and chronic pancreatitis in chronic alcoholic liver disease: coincidence or shared toxicity? Pancreas. 2014 Jul;43(5):730-4. doi: 10.1097/MPA.0000000000000085.</citation>
    <PMID>24713840</PMID>
  </results_reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>December 8, 2020</last_update_submitted>
  <last_update_submitted_qc>December 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Corporacion Parc Tauli</investigator_affiliation>
    <investigator_full_name>Jordi Sanchez-Delgado</investigator_full_name>
    <investigator_title>M.D; PhD</investigator_title>
  </responsible_party>
  <keyword>exocrine pancreatic insufficiency</keyword>
  <keyword>liver cirrhosis</keyword>
  <keyword>decompensated cirrhosis</keyword>
  <keyword>malnutrition</keyword>
  <keyword>prevalence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Exocrine Pancreatic Insufficiency</mesh_term>
    <mesh_term>Fibrosis</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/NCT03236038
org study id: 2017536
nct id: NCT03236038
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Exocrine pancreatic insufficiency (EPI) is the inability of the pancreas to perform a normal
      digestive function. The prevalence of IPE in patients with decompensated hepatic cirrhosis
      (HC) is unknown and most published series are short, old and use a single diagnostic
      technique with potential risk of false positives and negatives. Demonstrating IPE in a
      patient with HC can change their vital prognosis with the indication of pancreatic enzymes
      that can improve their nutritional status and help control their decompensations.

      Objectives: To assess the prevalence of IPE in patients with decompensated CH. To establish
      correlation between fecal elastase and 13C triolein breath test.

      Methodology: Unicentric, transversal study that will be carried out during hospitalization.
      Patients with HC who enter for decompensation and requiere hospitalization will be included
      consecutively. Exclusion criteria will include prior diagnosis of IPE, suspicion of biliary
      obstruction, more than 5 dep / d induced by laxatives or liquid stools.

      The diagnosis of IPE will be made with the combination of two techniques (13C triolein breath
      test and fecal elastase).

      Demographic, epidemiological data, clinical data as well as anthropometric parameters will be
      collected. A blood test will also be done to assess nutritional status and associated
      deficits. A multivariate analysis will be performed to assess the predictive factors of IPE
Exocrine pancreatic insufficiency (EPI) is defined as the inability of the pancreas to
      perform a normal digestive function. Habitually, it occurs as a result of a severe reduction
      in the secretion of pancreatic enzymes, although - less frequently - it may be due to the
      inability of these enzymes to perform their function. Clinically, it has a very broad
      spectrum of presentation with abdominal discomforts, malnutrition, chronic diarrhea and, in
      severe cases, steatorrhea. It must be said, however, that it is not until the disease is very
      evolved with a pancreatic function very deteriorated (more than 90%) that steatorrhea becomes
      clinically evident. In addition, the onset of symptoms triggered by the intake of fats makes
      these patients adapt their diet, often unconsciously, so it is not uncommon to find patients
      with EPI and constipation.

      To establish the diagnosis of IPE, different clinical tests are used. There are direct
      methods or invasive (secretin stimulation test, secretin-cerulein Lundh test) and noninvasive
      or indirect methods (coefficient of fat absorption, fecal elastase, fecal chymotrypsin
      activity, the pancreoleuril test, test with paraaminobenzoic acid and marked triolein test)
      are, in general, more accessible to the usual clinical practice.

      Regarding etiology, the most frequent cause of EPI is chronic pancreatitis, an entity that is
      closely linked to chronic alcohol consumption. On the one hand, it should be noted that
      alcohol is a common etiologic factor to both pathogenesis of pancreatic and liver affections.
      On the other hand, it is well known that the liver and pancreas have a close relationship
      with regard to their anatomy and physiology. The pancreatic duct and the coledocus bind to
      the level of the Vater papilla, so that their contents are mixed.

      Patients with EPI have severe malnutrition, a factor which increases the morbidity and
      mortality. Therefore, adequately replacing nutritional deficits by enzyme replacement therapy
      contributes significantly to decrease the complications, the hospital stays and the
      mortality. It could increase the quality of life of the patients. In addition, patients
      suffering from liver cirrhosis have other complications arising from malnutrition, as ascites
      that could be benefited from the improvement of the nutritional profile by enzyme replacement
      therapy detected in case of EPI. That is why we believe that our study could contribute to
      improving patient management with decompensated liver cirrhosis.

      The objective of the study is to assess the prevalence of exocrine pancreatic insufficiency
      EPI in patients with decompensated alcoholic liver cirrhosis.

      This is an epidemiological, unicentral, cross-sectional study that will be carried out within
      the hospital setting from October '17 to October'19.

      Patients diagnosed with liver cirrrhosis and enter the hepatology unit for clinical
      decompensation (sd hepatorenal, ascitic decompensation, hepatic encephalopathy,
      gastrointestinal bleeding stable) will be included .

      The investigators will collect demographic, epidemiology, analytic and clinical data.
      Anthropometric parameters such as tricipital fold, weight and size, will also be measured,
      which will allow the calculation of body mass index (BMI).

      In order to diagnose the presence of IPE, the breath test with triolein marked with 13C
      (Pancreo-Kit®) will be performed. The study consists of a delay of 8 hours (overnight) and
      later obtaining a basal sample through exhalation of air in a tube. Subsequently, a substrate
      (foods with marked triolein) will be administered to the patient and after 30 minutes, it
      will have to exhale air in a tube every 30 minutes for a total of 6 hours, thus obtaining a
      total of 13 samples.

      Blood tests will also be performed on all patients to assess their nutritional status (Hg,
      albumin, prealbumin, total proteins, cholesterol (HDL / LDL), bilirubin, prothrombin time,
      triglycerides, liposoluble Vitamins A, D, E and K; Vitamins B1, B12; calcium, phosphorus and
      magnesium), Hb glucose and collect a sample of solid stool isolated for the determination of
      the fecal elastase.
observational model: Other
time perspective: Prospective
measure: Prevalence of exocrine pancreatic insufficiency in decompensated alcoholic cirrhosis
time frame: This is a prevalence study. Outcome measure will be assessed during patient admision in the hospital. Data will be reported once the inclusion has been completed (2 years).
description: The diagnosis of EPI will be made through the combination of two diagnostic tests.
The labeled triolein breath test will use criteria established by the manufacturer of the product (Pancreo-Kit®) Isomed pharma.
Reference value: Normal: > 29%; Pathological: < 29% of the fat administered
The fecal elastase test (Bioserv Diagnostics (BS-86-01 Elastase Pancreatic ELISA) distributed by Palex Medical.)
A normal result will be considered: 200 to > 500 μg / g
Slight exocrine pancreatic insufficiency- Moderate: 100 - 200 μg / g
Severe exocrine pancreatic insufficiency: <100 μg / g
In those cases where both results are negative, it will be considered that there is no EPI. In cases where both results are positive, the diagnosis of EPI will be performed. If the results are discordant, a Sobel test or feces quantification test will be performed.
Coefficient of fat absorption; Pathological if elimination > 7g of fat / day with a diet of 100g fat / day.
intervention type: Diagnostic Test
intervention name: Labeled triolein urea breath test
description: The diagnosis of EPI will be made through the combination of two diagnostic tests.
The labeled triolein breath test will use criteria established by the manufacturer of the product (Pancreo-Kit®) Isomed pharma.
The fecal elastase test will be performed at our own center (Bioserv Diagnostics (BS-86-01 Elastase Pancreatic ELISA) distributed by Palex Medical.) In those cases where both results are negative, it will be considered that there is no EPI. In cases where both results are positive, the diagnosis of EPI will be performed. If the results are discordant, a Sobel test or feces quantification test will be performed.
other name: fecal elastase
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jordi Sánchez-Delgado, M.D; PhD
role: Principal Investigator
affiliation: Corporació Sanitària Parc Tauli
facility: 
country: Spain
citation: Aoufi Rabih S, Garcia Agudo R, Legaz Huidobro ML, Ynfante Ferrus M, Gonzalez Carro P, Perez Roldan F, Ruiz Carrillo F, Tenias Burillo JM. Exocrine pancreatic insufficiency and chronic pancreatitis in chronic alcoholic liver disease: coincidence or shared toxicity? Pancreas. 2014 Jul;43(5):730-4. doi: 10.1097/MPA.0000000000000085.
PMID: 24713840
responsible party type: Principal Investigator
investigator affiliation: Corporacion Parc Tauli
investigator full name: Jordi Sanchez-Delgado
investigator title: M.D; PhD
mesh term: Liver Cirrhosis
mesh term: Exocrine Pancreatic Insufficiency
mesh term: Fibrosis
sharing ipd: Undecided