<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/NCT02245165</url>
  </required_header>
  <id_info>
    <org_study_id>LNMMA-UU-02</org_study_id>
    <secondary_id>LNMMA-UU-02</secondary_id>
    <nct_id>NCT02245165</nct_id>
  </id_info>
  <brief_title>Nitric Oxide Control of Migrating Motor Complex: L-NMMA Effects in Relation to Receptor Blockades</brief_title>
  <acronym>LNMMA</acronym>
  <official_title>Nitric Oxide Control of the Migrating Motor Complex in Man: L-NMMA Effects in Relation to Muscarinic and Serotonergic Receptor Blockade</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bengt Ihre Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Swedish Society of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim is to elucidate how NO works in conjunction with other neurotransmitters to regulate&#xD;
      the migrating motility complex (MMC). Twenty-two healthy volunteers should undergo&#xD;
      water-perfused antroduodenojejunal manometry during a control period of 4 h, followed by&#xD;
      another 4h after a bolus injection of either saline or the NO synthase inhibitor&#xD;
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or&#xD;
      ondansetron (8 mg). Effects on the MMC pattern are determined. Exhaled and rectal NO is&#xD;
      monitored throughout the experiments. Effects of L-NMMA on the MMC pattern are analyzed&#xD;
      against a background of atropine or ondansetron. Blood samples are drawn for analysis of&#xD;
      simultaneous peptide hormone release into the bloodstream. Peptide hormone release will be&#xD;
      correlated to the respective motility pattern elicited by LNMMA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dysregulation of the cyclic motility pattern controlling propulsion during fasting, the&#xD;
      migrating motor complex (MMC), can result in small intestinal bacterial overgrowth and&#xD;
      symptoms of intestinal obstruction. Nitric oxide (NO) acts as an inhibitory neurotransmitter&#xD;
      by relaxation of smooth muscle cells. Little is known on how NO works in conjunction with&#xD;
      other neurotransmitters to regulate the MMC.&#xD;
&#xD;
      Methods: Twenty-two healthy volunteers (22-38 years) should undergo antroduodenojejunal&#xD;
      manometry recordings for 8h, 4h of which as a control period with basal motility recording&#xD;
      and 4h after a bolus injection of either saline or the NO synthase inhibitor&#xD;
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or&#xD;
      ondansetron (8 mg). The effects of L-NMMA on the MMC pattern are to be determined. Exhaled&#xD;
      and rectal NO was monitored throughout the experiments as a means to secure efficient NO&#xD;
      synthase inhibition.&#xD;
&#xD;
      Expected results: L-NMMA is expected to increase the intestinal motor activity, either as a&#xD;
      direct effect on the small muscle cells, or through the release of some motility-stimulating&#xD;
      gut peptide hormone (motility, ghrelin, somatostatin).&#xD;
&#xD;
      Expected conclusions: A NO donor, such as nitrite or nitrate which is converted to NO in an&#xD;
      acidic milieu in the stomach may act as an inhibitor of motility. Thus, swallowed nitrite and&#xD;
      nitrate from the saliva may contribute to the regulation of gastric emptying and&#xD;
      gastrointestinal motility.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect on phases I-III of the migrating motor complex</measure>
    <time_frame>1 year</time_frame>
    <description>NO is considered to be of importance for gastrointestinal motility. The MMC is measured as a biomarker of regulatory functions of gastrointestinal motility. Inhibition of the elaboration of NO by use of LNMMA is used to draw conclusions about the importance of NO for regulation of gastrointestinal motility.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduced exhaled NO after administration of NO synthase inhibitor LNMMA</measure>
    <time_frame>1 year</time_frame>
    <description>After administration of a Nitric oxide synthase (NOS) inhibitor exhaled NO is used as a marker of reduced NOS activity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Gastrointestinal Motility Disorder</condition>
  <condition>Disturbance of Salivary Secretion</condition>
  <arm_group>
    <arm_group_label>Nitric oxide synthase (NOS) inhibition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a control period of 4 hours, intervention with L-NMMA (10 mg/kg IV) is done and recording continued for 4 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>After a control period of 4 hours, intervention with saline is done and recording continued for 4 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV</intervention_name>
    <arm_group_label>Nitric oxide synthase (NOS) inhibition</arm_group_label>
    <other_name>L-NMMA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>saline</intervention_name>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers 18-50 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18, or &gt; 50 years&#xD;
&#xD;
          -  Any disease&#xD;
&#xD;
          -  Any medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per M Hellstrom, MD, prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uppsala University</name>
      <address>
        <city>Uppsala</city>
        <state>Uppsala county</state>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>May 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>September 16, 2014</last_update_submitted>
  <last_update_submitted_qc>September 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nitric oxide</keyword>
  <keyword>Nitric oxide synthase</keyword>
  <keyword>Gastrointestinal motility</keyword>
  <keyword>Gut peptide hormones</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>omega-N-Methylarginine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02245165
org study id: LNMMA-UU-02
secondary id: LNMMA-UU-02
nct id: NCT02245165
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The aim is to elucidate how NO works in conjunction with other neurotransmitters to regulate
      the migrating motility complex (MMC). Twenty-two healthy volunteers should undergo
      water-perfused antroduodenojejunal manometry during a control period of 4 h, followed by
      another 4h after a bolus injection of either saline or the NO synthase inhibitor
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or
      ondansetron (8 mg). Effects on the MMC pattern are determined. Exhaled and rectal NO is
      monitored throughout the experiments. Effects of L-NMMA on the MMC pattern are analyzed
      against a background of atropine or ondansetron. Blood samples are drawn for analysis of
      simultaneous peptide hormone release into the bloodstream. Peptide hormone release will be
      correlated to the respective motility pattern elicited by LNMMA.
Dysregulation of the cyclic motility pattern controlling propulsion during fasting, the
      migrating motor complex (MMC), can result in small intestinal bacterial overgrowth and
      symptoms of intestinal obstruction. Nitric oxide (NO) acts as an inhibitory neurotransmitter
      by relaxation of smooth muscle cells. Little is known on how NO works in conjunction with
      other neurotransmitters to regulate the MMC.

      Methods: Twenty-two healthy volunteers (22-38 years) should undergo antroduodenojejunal
      manometry recordings for 8h, 4h of which as a control period with basal motility recording
      and 4h after a bolus injection of either saline or the NO synthase inhibitor
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or
      ondansetron (8 mg). The effects of L-NMMA on the MMC pattern are to be determined. Exhaled
      and rectal NO was monitored throughout the experiments as a means to secure efficient NO
      synthase inhibition.

      Expected results: L-NMMA is expected to increase the intestinal motor activity, either as a
      direct effect on the small muscle cells, or through the release of some motility-stimulating
      gut peptide hormone (motility, ghrelin, somatostatin).

      Expected conclusions: A NO donor, such as nitrite or nitrate which is converted to NO in an
      acidic milieu in the stomach may act as an inhibitor of motility. Thus, swallowed nitrite and
      nitrate from the saliva may contribute to the regulation of gastric emptying and
      gastrointestinal motility.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Effect on phases I-III of the migrating motor complex
time frame: 1 year
description: NO is considered to be of importance for gastrointestinal motility. The MMC is measured as a biomarker of regulatory functions of gastrointestinal motility. Inhibition of the elaboration of NO by use of LNMMA is used to draw conclusions about the importance of NO for regulation of gastrointestinal motility.
measure: Reduced exhaled NO after administration of NO synthase inhibitor LNMMA
time frame: 1 year
description: After administration of a Nitric oxide synthase (NOS) inhibitor exhaled NO is used as a marker of reduced NOS activity.
arm group label: Nitric oxide synthase (NOS) inhibition
arm group type: Experimental
description: After a control period of 4 hours, intervention with L-NMMA (10 mg/kg IV) is done and recording continued for 4 hours.
arm group label: Saline
arm group type: Sham Comparator
description: After a control period of 4 hours, intervention with saline is done and recording continued for 4 hours.
intervention type: Biological
intervention name: L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV
arm group label: Nitric oxide synthase (NOS) inhibition
other name: L-NMMA
intervention type: Biological
intervention name: saline
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Per M Hellstrom, MD, prof
role: Principal Investigator
affiliation: Uppsala University
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: omega-N-Methylarginine