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/NCT06009939</url>
    </required_header>
    <id_info>
      <org_study_id>2023-01</org_study_id>
      <nct_id>NCT06009939</nct_id>
    </id_info>
    <brief_title>Microvascular Sex and Age-related Day-to-day Variability in Healthy Subjects</brief_title>
    <official_title>Microvascular Sex and Age-related Day-to-day Variability in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Vårdcentralen Åby</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Department of Biomedical Engineering (IMT)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Department of Health, Medicine and Caring Sciences (HMV)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Linkoeping University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Vårdcentralen Åby</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 goal of this observational study is to learn more about the microcirculation in the skin&#xD;
        by examining sex and age-related day-to-day variability in healthy subjects. The main&#xD;
        questions the trial aims to answer are:&#xD;
  &#xD;
          -  What is the day-to-day variability of the optical measurement techniques in the&#xD;
             microcirculation, and does age and gender affect this?&#xD;
  &#xD;
          -  Does the day-to-day variability differ in the foot compared to the arm?&#xD;
  &#xD;
        Participants will rest whilst skin measurement by optical measurement techniques are&#xD;
        performed. Baseline measurements and post-occlusive reactive hyperemia will be studied on the&#xD;
        forearm and foot. This measurement procedure is repeated within one week, in order to study&#xD;
        variability.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The microcirculation consists of arterioles, capillaries and venules and is essential for&#xD;
        nutrients and oxygen to be delivered to the tissue as well as waste products to be removed.&#xD;
        The skin is often used as a model for studying microcirculation.&#xD;
  &#xD;
        There are many different ways to study the microcirculation, most commonly are noninvasive&#xD;
        optical techniques which measures the reflection of light used. Laser Doppler Flowmetry (LDF)&#xD;
        has been the golden standard, but one limitation with the technique is that it measures the&#xD;
        bloodflow in a small area (about 1 mm3). In this study the investigators will be using&#xD;
        single-point measurement with a technique called EPOS and larger area measurements with a&#xD;
        technique called PSI-X. EPOS, based on LDF and diffuse reflectance spectroscopy (DRS),&#xD;
        analyze speed-resolved perfusion, variations in red blood cell tissue fraction, oxygen&#xD;
        saturation and vessel diameter. PSI-X, based on multi-exposure laser speckle contrast imaging&#xD;
        (MELSCI) and multispectral imaging (MSI), analyze conventional perfusion, speed-resolved&#xD;
        perfusion and oxygen saturation.&#xD;
  &#xD;
        Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global&#xD;
        and local regulation of the vessels and can be studied using frequency analysis of&#xD;
        time-resolved blood flow signals. Since EPOS and PSI-X collect data of time-resolved blood&#xD;
        flow, flowmotion analysis will also be conducted in the study.&#xD;
  &#xD;
        To study day-to-day variability, data will be collected from each subject on two separate&#xD;
        days within seven days, on the same location of the foot as well as the arm. Once the subject&#xD;
        arrives to the lab, a questionnaire will be filled in regarding the subjects physical&#xD;
        activity level, exercise habits and usage of medication and nicotine. The subject will also&#xD;
        confirm to not have eaten two hours and not used nicotine or caffeine three hours prior to&#xD;
        the experiment. Thereafter the subject's length and weight will be measured and BMI&#xD;
        calculated. The subjects skin type will be determined using the Fitzpatrick scale. All of&#xD;
        this is only done on the first day of measurement, on the second day the subject will skip&#xD;
        right to the following part.&#xD;
  &#xD;
        An acclimatization period of 15 minutes begins and the subject will remove socks and lay&#xD;
        down. While the subject rests the equipment will be set up. A blood pressure cuff is placed&#xD;
        around the upper arm as well as around the ankle. An EPOS-probe is placed on the dorsal side&#xD;
        of the foot as well as the volar side of the forearm. A marker pen is used to mark the skin&#xD;
        around the probes which enables the probe to be placed on the same location on the next&#xD;
        measurement. Once five minutes has passed, the subject's blood pressure and pulse is noted.&#xD;
        Thereafter the PSI-X camera is set up and angled to film the plantar side of the foot from a&#xD;
        distance of about 25 cm. The subject is asked to lay as still as possible during the&#xD;
        measurement. Once the acclimatization period has passed, the lights in the lab are turned off&#xD;
        and the measurement will begin. Firstly baseline data will be collected as the subject rest&#xD;
        for 10 minutes without provocation. Thereafter the blood pressure cuff on the ankle will&#xD;
        inflate to 250 mmHg for five minutes whilst data is collected. Lastly data is collected for&#xD;
        five minutes after the blood pressure cuff deflates. Thereafter the PSI-X camera is moved and&#xD;
        angled to film the forearm from a 25 cm distance. The protocol described above is repeated&#xD;
        for the arm. The subject will return within seven days to repeat the data collection&#xD;
        protocol.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">March 1, 2023</start_date>
    <completion_date type="Actual">September 14, 2023</completion_date>
    <primary_completion_date type="Actual">September 14, 2023</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>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Speed-resolved perfusion</measure>
      <time_frame>Measured during 45 minutes and at one more occasion for 45 minutes within one week.</time_frame>
      <description>[% RBC ×mm/s]</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Red blood cell tissue fraction</measure>
      <time_frame>Measured during 45 minutes and at one more occasion for 45 minutes within one week.</time_frame>
      <description>[% RBC]</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygen saturation</measure>
      <time_frame>Measured during 45 minutes and at one more occasion for 45 minutes within one week.</time_frame>
      <description>[% oxygen]</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vessel diameter</measure>
      <time_frame>Measured during 45 minutes and at one more occasion for 45 minutes within one week.</time_frame>
      <description>[μm]</description>
    </primary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Actual">48</enrollment>
    <condition>Healthy Subjects</condition>
    <arm_group>
      <arm_group_label>Healthy men aged 20-30 years old</arm_group_label>
      <description>Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.&#xD;
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy women aged 20-30 years old</arm_group_label>
      <description>Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.&#xD;
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy men aged 50-60 years old</arm_group_label>
      <description>Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.&#xD;
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy women aged 50-60 years old</arm_group_label>
      <description>Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.&#xD;
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Occlusion of the circulation in the arm and foot</intervention_name>
      <description>A blood pressure cuff occludes the circulation in the upper arm as well as around the ankle.</description>
      <arm_group_label>Healthy men aged 20-30 years old</arm_group_label>
      <arm_group_label>Healthy men aged 50-60 years old</arm_group_label>
      <arm_group_label>Healthy women aged 20-30 years old</arm_group_label>
      <arm_group_label>Healthy women aged 50-60 years old</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          12 healthy men and 12 healthy women aged 20-30 years old. 12 healthy men and 12 healthy&#xD;
          women aged 50-60 years old.&#xD;
  &#xD;
          In total 48 participants will be included.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Men and women between 20-30 years old and 50-60 years old&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Regular use of medication (except for anti-conception medication)&#xD;
  &#xD;
            -  Hypertension&#xD;
  &#xD;
            -  Skin- or cardiovascular disease&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Since the investigators aim to study potential differences between men and women an equal number of men and women needs to be included in the study.</gender_description>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fredrik Iredahl</last_name>
      <role>Principal Investigator</role>
      <affiliation>Linköping University, Department of Health, Medicine and Caring Sciences</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Linköping University</name>
        <address>
          <city>Linköping</city>
          <state>Östergötland</state>
          <zip>58185</zip>
          <country>Sweden</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Sweden</country>
    </location_countries>
    <reference>
      <citation>Hultman M, Larsson M, Stromberg T, Henricson J, Iredahl F, Fredriksson I. Flowmotion imaging analysis of spatiotemporal variations in skin microcirculatory perfusion. Microvasc Res. 2023 Mar;146:104456. doi: 10.1016/j.mvr.2022.104456. Epub 2022 Nov 18. No abstract available.</citation>
      <PMID>36403668</PMID>
    </reference>
    <reference>
      <citation>Fredriksson I, Larsson M, Stromberg T, Iredahl F. Vasomotion analysis of speed resolved perfusion, oxygen saturation, red blood cell tissue fraction, and vessel diameter: Novel microvascular perspectives. Skin Res Technol. 2022 Jan;28(1):142-152. doi: 10.1111/srt.13106. Epub 2021 Nov 10.</citation>
      <PMID>34758168</PMID>
    </reference>
    <reference>
      <citation>Hultman M, Larsson M, Stromberg T, Fredriksson I. Real-time video-rate perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning. J Biomed Opt. 2020 Nov;25(11):116007. doi: 10.1117/1.JBO.25.11.116007.</citation>
      <PMID>33191685</PMID>
    </reference>
    <reference>
      <citation>Hultman M, Larsson M, Stromberg T, Fredriksson I. Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning. J Biomed Opt. 2023 Mar;28(3):036007. doi: 10.1117/1.JBO.28.3.036007. Epub 2023 Mar 20.</citation>
      <PMID>36950019</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Vårdcentralen Åby</investigator_affiliation>
      <investigator_full_name>Fredrik Iredahl</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>September 5, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT06009939/Prot_000.pdf</document_url>
      </provided_document>
      <provided_document>
        <document_type>Statistical Analysis Plan</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>September 5, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT06009939/SAP_001.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT06009939
  org study id: 2023-01
  nct id: NCT06009939
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this observational study is to learn more about the microcirculation in the skin
        by examining sex and age-related day-to-day variability in healthy subjects. The main
        questions the trial aims to answer are:
  
          -  What is the day-to-day variability of the optical measurement techniques in the
             microcirculation, and does age and gender affect this?
  
          -  Does the day-to-day variability differ in the foot compared to the arm?
  
        Participants will rest whilst skin measurement by optical measurement techniques are
        performed. Baseline measurements and post-occlusive reactive hyperemia will be studied on the
        forearm and foot. This measurement procedure is repeated within one week, in order to study
        variability.
  The microcirculation consists of arterioles, capillaries and venules and is essential for
        nutrients and oxygen to be delivered to the tissue as well as waste products to be removed.
        The skin is often used as a model for studying microcirculation.
  
        There are many different ways to study the microcirculation, most commonly are noninvasive
        optical techniques which measures the reflection of light used. Laser Doppler Flowmetry (LDF)
        has been the golden standard, but one limitation with the technique is that it measures the
        bloodflow in a small area (about 1 mm3). In this study the investigators will be using
        single-point measurement with a technique called EPOS and larger area measurements with a
        technique called PSI-X. EPOS, based on LDF and diffuse reflectance spectroscopy (DRS),
        analyze speed-resolved perfusion, variations in red blood cell tissue fraction, oxygen
        saturation and vessel diameter. PSI-X, based on multi-exposure laser speckle contrast imaging
        (MELSCI) and multispectral imaging (MSI), analyze conventional perfusion, speed-resolved
        perfusion and oxygen saturation.
  
        Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global
        and local regulation of the vessels and can be studied using frequency analysis of
        time-resolved blood flow signals. Since EPOS and PSI-X collect data of time-resolved blood
        flow, flowmotion analysis will also be conducted in the study.
  
        To study day-to-day variability, data will be collected from each subject on two separate
        days within seven days, on the same location of the foot as well as the arm. Once the subject
        arrives to the lab, a questionnaire will be filled in regarding the subjects physical
        activity level, exercise habits and usage of medication and nicotine. The subject will also
        confirm to not have eaten two hours and not used nicotine or caffeine three hours prior to
        the experiment. Thereafter the subject's length and weight will be measured and BMI
        calculated. The subjects skin type will be determined using the Fitzpatrick scale. All of
        this is only done on the first day of measurement, on the second day the subject will skip
        right to the following part.
  
        An acclimatization period of 15 minutes begins and the subject will remove socks and lay
        down. While the subject rests the equipment will be set up. A blood pressure cuff is placed
        around the upper arm as well as around the ankle. An EPOS-probe is placed on the dorsal side
        of the foot as well as the volar side of the forearm. A marker pen is used to mark the skin
        around the probes which enables the probe to be placed on the same location on the next
        measurement. Once five minutes has passed, the subject's blood pressure and pulse is noted.
        Thereafter the PSI-X camera is set up and angled to film the plantar side of the foot from a
        distance of about 25 cm. The subject is asked to lay as still as possible during the
        measurement. Once the acclimatization period has passed, the lights in the lab are turned off
        and the measurement will begin. Firstly baseline data will be collected as the subject rest
        for 10 minutes without provocation. Thereafter the blood pressure cuff on the ankle will
        inflate to 250 mmHg for five minutes whilst data is collected. Lastly data is collected for
        five minutes after the blood pressure cuff deflates. Thereafter the PSI-X camera is moved and
        angled to film the forearm from a 25 cm distance. The protocol described above is repeated
        for the arm. The subject will return within seven days to repeat the data collection
        protocol.
  observational model: Cohort
  time perspective: Prospective
  measure: Speed-resolved perfusion
  time frame: Measured during 45 minutes and at one more occasion for 45 minutes within one week.
  description: [% RBC ×mm/s]
  measure: Red blood cell tissue fraction
  time frame: Measured during 45 minutes and at one more occasion for 45 minutes within one week.
  description: [% RBC]
  measure: Oxygen saturation
  time frame: Measured during 45 minutes and at one more occasion for 45 minutes within one week.
  description: [% oxygen]
  measure: Vessel diameter
  time frame: Measured during 45 minutes and at one more occasion for 45 minutes within one week.
  description: [μm]
  arm group label: Healthy men aged 20-30 years old
  description: Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  arm group label: Healthy women aged 20-30 years old
  description: Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  arm group label: Healthy men aged 50-60 years old
  description: Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  arm group label: Healthy women aged 50-60 years old
  description: Foot: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  Arm: 10 minutes of baseline measurement, 5 minutes of occlusion and 5 minutes of Post-occlusive reactive hyperemia (PORH) measurement.
  intervention type: Other
  intervention name: Occlusion of the circulation in the arm and foot
  description: A blood pressure cuff occludes the circulation in the upper arm as well as around the ankle.
  arm group label: Healthy men aged 20-30 years old
  arm group label: Healthy men aged 50-60 years old
  arm group label: Healthy women aged 20-30 years old
  arm group label: Healthy women aged 50-60 years old
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  gender based: Yes
  gender description: Since the investigators aim to study potential differences between men and women an equal number of men and women needs to be included in the study.
  minimum age: 20 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Fredrik Iredahl
  role: Principal Investigator
  affiliation: Linköping University, Department of Health, Medicine and Caring Sciences
  facility: 
  country: Sweden
  citation: Hultman M, Larsson M, Stromberg T, Henricson J, Iredahl F, Fredriksson I. Flowmotion imaging analysis of spatiotemporal variations in skin microcirculatory perfusion. Microvasc Res. 2023 Mar;146:104456. doi: 10.1016/j.mvr.2022.104456. Epub 2022 Nov 18. No abstract available.
  PMID: 36403668
  citation: Fredriksson I, Larsson M, Stromberg T, Iredahl F. Vasomotion analysis of speed resolved perfusion, oxygen saturation, red blood cell tissue fraction, and vessel diameter: Novel microvascular perspectives. Skin Res Technol. 2022 Jan;28(1):142-152. doi: 10.1111/srt.13106. Epub 2021 Nov 10.
  PMID: 34758168
  citation: Hultman M, Larsson M, Stromberg T, Fredriksson I. Real-time video-rate perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning. J Biomed Opt. 2020 Nov;25(11):116007. doi: 10.1117/1.JBO.25.11.116007.
  PMID: 33191685
  citation: Hultman M, Larsson M, Stromberg T, Fredriksson I. Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning. J Biomed Opt. 2023 Mar;28(3):036007. doi: 10.1117/1.JBO.28.3.036007. Epub 2023 Mar 20.
  PMID: 36950019
  responsible party type: Principal Investigator
  investigator affiliation: Vårdcentralen Åby
  investigator full name: Fredrik Iredahl
  investigator title: Associate Professor
  provided document: 
  provided document: 