xml: <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/NCT06003608</url>
    </required_header>
    <id_info>
      <org_study_id>M007-PD-001</org_study_id>
      <nct_id>NCT06003608</nct_id>
    </id_info>
    <brief_title>Observational Small Intestine and Blood Fingerprint (SmIle) Study in Parkinson's Disease</brief_title>
    <acronym>SmIle</acronym>
    <official_title>Observational, Cross-sectional Clinical Study in Parkinson's Disease (PD) Patients and Healthy Controls (HC) to Identify PD Specific Microbial and Metabolic Fingerprints in Small Intestinal (SI) Fluid and Blood</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nimble Science Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>MRM Health N.V.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Nimble Science Ltd.</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Observational cross-sectional study in PD patients and healthy controls (HC) using an&#xD;
        investigational medical device consisting of a passive small intestine microbiome aspiration&#xD;
        (SIMBA) system (capsule) that is ingested orally and recovered together with the stools (home&#xD;
        recovery) together with blood sampling (during the onsite visit).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants will be swallowing two SIMBA capsules which allows for minimally-invasive&#xD;
        sampling of the microbiome and metabolome deep in the small intestine. Researchers will use&#xD;
        the capsule samples to determine the small intestinal microbiome and metabolomic signatures&#xD;
        in luminal fluid samples from the small bowel in Parkinson Disease (PD) patients compared to&#xD;
        healthy controls (HC).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">March 2024</completion_date>
    <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Difference in microbiome profile of small intestine samples between groups</measure>
      <time_frame>Baseline</time_frame>
      <description>Functional dysbiosis profile of the small intestinal microbiota of Parkinson's Disease patients compared to age-matched neurotypical controls, as determined by whole metagenome shotgun sequencing based profiling</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Difference in blood metabolome composition between groups</measure>
      <time_frame>Baseline</time_frame>
      <description>Blood metabolome composition profile of Parkinson's Disease patients as compared to age-matched neurotypical controls, as determined by metabolomics analysis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between the observed small intestine microbiome profile and blood metabolome composition, including, in PD subjects, levodopa pharmacodynamics</measure>
      <time_frame>Baseline</time_frame>
      <description>Small intestinal and blood pharmacodynamics of Levodopa as a function of small intestinal microbiota profiles, as determined by blood and small intestinal metabolomics and small intestinal whole metagenome shotgun profiling and appropriate statistical correlation methods</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Parkinson Disease</condition>
    <arm_group>
      <arm_group_label>Healthy control (HC)</arm_group_label>
      <description>25 neurotypical controls, age-matched to the Parkinson's disease group</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Parkinson's disease (PD)</arm_group_label>
      <description>75 Parkinson's disease patients</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Fluid biopsy capsule</intervention_name>
      <description>Ingestion of two SIMBA capsules</description>
      <arm_group_label>Healthy control (HC)</arm_group_label>
      <arm_group_label>Parkinson's disease (PD)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Levodopa-Carbidopa Immediate Release</intervention_name>
      <description>Single dose, Levodopa-Carbidopa Immediate Release</description>
      <arm_group_label>Parkinson's disease (PD)</arm_group_label>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Whole Blood sample, Stool sample, Fluid from small intestine&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Eligibility will be determined based on information reported by the subject and the results&#xD;
          of the screening assessments (physical exam, etc). Prospective approval of protocol&#xD;
          deviations to recruitment and enrollment criteria, also known as protocol waivers or&#xD;
          exemptions, is not permitted.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
          Subjects are eligible to be included in the study only if all of the following criteria&#xD;
          apply:&#xD;
  &#xD;
            1. Males and females aged 50-85 years old at time of on-site visit&#xD;
  &#xD;
            2. Signed Informed consent&#xD;
  &#xD;
            3. Willing &amp; able to comply with study procedures (including SIMBA capsule ingestion) and&#xD;
               have study assessments performed&#xD;
  &#xD;
            4. Able to swallow a size-00 capsule (23mm length) in OFF state Additional inclusion&#xD;
               criteria for PD patients only&#xD;
  &#xD;
            5. Diagnosis of idiopathic PD (Clinically Probable PD), including documented levodopa&#xD;
               responsiveness&#xD;
  &#xD;
            6. Treatment with an immediate release levodopa formulation during the day at a stable&#xD;
               dose for at least 2 months prior to enrollment&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
          Subjects are excluded from the study if any of the following criteria apply:&#xD;
  &#xD;
            1. Any risk of capsule non-excretion, including, e.g., prior gastrointestinal disease,&#xD;
               surgery, or radiation treatment which, in the Investigator's opinion, would lead to&#xD;
               intestinal structuring or obstruction, achalasia, eosinophilic esophagitis, any&#xD;
               inflammatory bowel disease (IBD), cancer diagnosis or treatment within the past year,&#xD;
               or previous esophageal, gastric, small intestinal, or colonic surgery; appendectomy or&#xD;
               cholecystectomy more than 3 months prior to on-site study visit are acceptable,&#xD;
  &#xD;
            2. Use of any medications in the week prior to the on-site study visit, unless part of&#xD;
               regular treatment, that could substantially alter gastrointestinal motor function&#xD;
               (e.g., opioids, prokinetics, anticholinergics); laxative use is allowed provided that&#xD;
               it is kept unchanged in the week prior to the study visit. PPIs are allowed provided a&#xD;
               wash-out period of 48 hours is respected before swallowing the SIMBA capsules and PPI&#xD;
               treatment is resumed only 4 hours thereafter,&#xD;
  &#xD;
            3. Any contraindication for using domperidone, including a long QT interval, concomitant&#xD;
               use of QT prolonging drugs, any risk of significant electrolyte abnormality, known&#xD;
               hypersensitivity, known liver impairment or significant (e.g. unstable) cardiac&#xD;
               disease (see label) putting the subject at significant risk according to the&#xD;
               investigator's clinical judgement&#xD;
  &#xD;
            4. History of oropharyngeal dysphagia, or other swallowing disorder with a risk of&#xD;
               capsule aspiration, e.g. SDQ score &gt; 4,&#xD;
  &#xD;
            5. Any concomitant PD treatment, including any dopamine agonist and MAO-B inhibitor,&#xD;
               except (for PD patients only) an immediate release levodopa formulation during the day&#xD;
               (required per inclusion criterion), the concomitant use of a decarboxylase inhibitor&#xD;
               and the use of a controlled release levodopa formulation at bedtime,&#xD;
  &#xD;
            6. Major genital and/or rectum prolapse,&#xD;
  &#xD;
            7. Any concomitant or previous treatment (&lt;2 months from on-site study visit) with&#xD;
               significant anti-inflammatory or immune suppressant medication, e.g. DMARDs,&#xD;
               biologicals or systemic corticosteroids, except non-chronic PRN use of an NSAID and/or&#xD;
               5-ASA (mesalazine) treatment,&#xD;
  &#xD;
            8. Active cancer, including any prolactinoma, within 5 years (allowed: uncomplicated&#xD;
               basal cell carcinoma and successfully removed carcinoma in situ),&#xD;
  &#xD;
            9. Clinically significant immune deficiency (according to Investigator's judgement),&#xD;
  &#xD;
           10. Documented HIV infection, or any clinically significant systemic infection,&#xD;
  &#xD;
           11. Antibiotic use (except for local use), use of prebiotics, or probiotics ≤12 weeks&#xD;
               prior to on-site study visit, or Fecal Microbiota Transplantation anytime in medical&#xD;
               history&#xD;
  &#xD;
           12. Dementia in medical history or identified by a MMSE &lt;24,&#xD;
  &#xD;
           13. Insulin-dependent diabetes mellitus,&#xD;
  &#xD;
           14. Current Psychosis episode by clinical judgement based on anamnesis&#xD;
  &#xD;
           15. Active significant impulse control disorder (by clinical judgement and based on&#xD;
               interview and medical records)&#xD;
  &#xD;
           16. Pregnancy&#xD;
  &#xD;
           17. Alcohol or drug abuse&#xD;
  &#xD;
           18. Deep brain stimulation or Duodopa/Lecigon treatment.&#xD;
  &#xD;
           19. Subject, according to investigator assessment, not expected to be able to comply with&#xD;
               study procedures including SIMBA capsule recovery and SIBO breath test execution with&#xD;
               - or without help (when home).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Davide Martino, MD PHD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Calgary</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Davide Martino, MD PhD</last_name>
      <phone>403-210-8726</phone>
      <email>davide.martino@ucalgary.ca</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Calgary</name>
        <address>
          <city>Calgary</city>
          <state>Alberta</state>
          <zip>T2N 1N4</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Parkinson Disease</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Levodopa</mesh_term>
      <mesh_term>Carbidopa</mesh_term>
      <mesh_term>Carbidopa, levodopa drug combination</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003608
  org study id: M007-PD-001
  nct id: NCT06003608
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Observational cross-sectional study in PD patients and healthy controls (HC) using an
        investigational medical device consisting of a passive small intestine microbiome aspiration
        (SIMBA) system (capsule) that is ingested orally and recovered together with the stools (home
        recovery) together with blood sampling (during the onsite visit).
  Participants will be swallowing two SIMBA capsules which allows for minimally-invasive
        sampling of the microbiome and metabolome deep in the small intestine. Researchers will use
        the capsule samples to determine the small intestinal microbiome and metabolomic signatures
        in luminal fluid samples from the small bowel in Parkinson Disease (PD) patients compared to
        healthy controls (HC).
  observational model: Cohort
  time perspective: Cross-Sectional
  measure: Difference in microbiome profile of small intestine samples between groups
  time frame: Baseline
  description: Functional dysbiosis profile of the small intestinal microbiota of Parkinson's Disease patients compared to age-matched neurotypical controls, as determined by whole metagenome shotgun sequencing based profiling
  measure: Difference in blood metabolome composition between groups
  time frame: Baseline
  description: Blood metabolome composition profile of Parkinson's Disease patients as compared to age-matched neurotypical controls, as determined by metabolomics analysis
  measure: Correlation between the observed small intestine microbiome profile and blood metabolome composition, including, in PD subjects, levodopa pharmacodynamics
  time frame: Baseline
  description: Small intestinal and blood pharmacodynamics of Levodopa as a function of small intestinal microbiota profiles, as determined by blood and small intestinal metabolomics and small intestinal whole metagenome shotgun profiling and appropriate statistical correlation methods
  arm group label: Healthy control (HC)
  description: 25 neurotypical controls, age-matched to the Parkinson's disease group
  arm group label: Parkinson's disease (PD)
  description: 75 Parkinson's disease patients
  intervention type: Device
  intervention name: Fluid biopsy capsule
  description: Ingestion of two SIMBA capsules
  arm group label: Healthy control (HC)
  arm group label: Parkinson's disease (PD)
  intervention type: Drug
  intervention name: Levodopa-Carbidopa Immediate Release
  description: Single dose, Levodopa-Carbidopa Immediate Release
  arm group label: Parkinson's disease (PD)
  Whole Blood sample, Stool sample, Fluid from small intestine
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 85 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Davide Martino, MD PHD
  role: Principal Investigator
  affiliation: University of Calgary
  last name: Davide Martino, MD PhD
  phone: 403-210-8726
  email: davide.martino@ucalgary.ca
  facility: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Parkinson Disease
  mesh term: Levodopa
  mesh term: Carbidopa
  mesh term: Carbidopa, levodopa drug combination
  sharing ipd: No