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/NCT05991609</url>
    </required_header>
    <id_info>
      <org_study_id>321662</org_study_id>
      <nct_id>NCT05991609</nct_id>
    </id_info>
    <brief_title>Extreme Morphology and Metabolic Health</brief_title>
    <official_title>Establishing the Metabolic and Nutritional Requirements of Individuals With Extreme Body Morphology</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Bath</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Bristol</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Bath</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>
        Researchers at the University of Bath are investigating the metabolism of individuals with&#xD;
        extreme body size, including those with skeletal dysplasia (commonly known as dwarfism), to&#xD;
        manage health risks such as heart disease. By better understanding how body size could change&#xD;
        how the body processes food, or how being bigger or smaller may influence eating habits,&#xD;
        healthy living guidelines to tackle issues such as obesity and overweight in these&#xD;
        populations can be improved. With help from expertise in the psychology field, this research&#xD;
        will also investigate whether the mental health of these individuals has been affected by&#xD;
        their size. On the whole, this study will involve one 24-hour visit to a research laboratory&#xD;
        at the University of Bath, followed by a 2-week monitoring period to capture 'normal'&#xD;
        physical activity and eating routines.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        After signing informed consent to take part in the study, participants will be asked to&#xD;
        complete a health entry criteria questionnaire, including a physical activity readiness&#xD;
        questionnaire and Eating Disorder Examination Questionnaire, to confirm eligibility.&#xD;
        Participants will also be required to complete a health questionnaire for administration of&#xD;
        anaesthetic as part of the biopsy procedure. Individuals who are very small or very big&#xD;
        (without skeletal dysplasia) will be asked to attend the laboratory for a pre-trial screening&#xD;
        as an additional eligibility criterion. This will involve measuring height, body mass, and&#xD;
        standing on a specialised scale (bioelectrical impedance scale) which estimates how much&#xD;
        muscle and fat someone has. If it is suspected that the participant meets the stated fat-free&#xD;
        mass criteria, a complete a full body Dual Energy X-ray Absorptiometry (DEXA) scan to assess&#xD;
        body composition more accurately will be completed. This involves lying flat on a bed for ~7&#xD;
        minutes and resting whilst the scan takes place. The research team will then inform the&#xD;
        participant after analysing the scan results if they are eligible and can continue with the&#xD;
        study.&#xD;
  &#xD;
        All participants deemed eligible who are able and willing to take part will be invited to&#xD;
        attend the University of Bath Human Physiology Laboratory for the full trial.&#xD;
  &#xD;
        On day 1, prior to attending the University of Bath participants will be asked to eat a&#xD;
        standardised diet of a cereal breakfast, and a supermarket purchased sandwich, drink and&#xD;
        snack meal deal for lunch, with self-selected quantities. Participants will ideally be fasted&#xD;
        for 4-5 hours before arrival (~17:00).&#xD;
  &#xD;
        Upon arrive at the University, individuals with skeletal dysplasia will also be asked to&#xD;
        complete the health entry criteria questionnaire and physical activity readiness&#xD;
        questionnaire to ensure eligibility. It is important that participants let the researchers&#xD;
        know of any medical conditions or any change in circumstance since signing up. All&#xD;
        information is strictly confidential.&#xD;
  &#xD;
        The research team will first take measurements of height, body mass, waist and hip&#xD;
        circumference, abdomen diameter (distance from your front to back), sitting height and blood&#xD;
        pressure. Early into the visit, participants will also be briefed on collecting urine into&#xD;
        provided containers. Individuals with skeletal dysplasia will then have a Dual Energy X-ray&#xD;
        Absorptiometry (DEXA) scan to assess body composition. All participants will also have a&#xD;
        Peripheral Quantitative Computed Tomography (pQCT) scan which involves placing one leg into a&#xD;
        round scanner to assess the tissues in your leg e.g., bone, muscle and fat (as if the image&#xD;
        were a slice). The scan requires you to keep your leg still for ~10 minutes.&#xD;
  &#xD;
        Participants will then be asked to rest in a bed and relax. In a seated position,&#xD;
        participants will complete a lung function test at rest which requires blowing into a&#xD;
        specialised device through a mouthpiece. Following this, after lying down and being briefed&#xD;
        on the procedure, a trained member of staff will take a fat tissue biopsy from the abdomen to&#xD;
        analyse genes and proteins in the cells. The fat biopsy involves inserting a needle with&#xD;
        suction just below the skin to extract the cells and will be performed under local&#xD;
        anaesthetic. This procedure may cause a bruise for up to 7 days. Following on from this, a&#xD;
        muscle biopsy will be taken from the quadriceps (large muscle on the front of the thigh) to&#xD;
        again measure genes and proteins as well as signalling pathways involved in our metabolism.&#xD;
        The needle is inserted just inside the muscle and 2/3 snips of tissue are collected. The&#xD;
        research team will provide information and equipment for aftercare of the biopsy sites to&#xD;
        prevent infection after participants leave the laboratory.&#xD;
  &#xD;
        Participants will then be provided with a hot meal for dinner. This will be a standard&#xD;
        portion of Sainsbury's Love Your Veg! Lentil Cottage Pie (400 g, serves 1). Prior to turning&#xD;
        the lights out at 22:00, participants will be fitted with sleep monitoring kit known as&#xD;
        polysomnography. The equipment includes an abdominal and chest pressure sensing band, a nasal&#xD;
        cannula and some sticky sensors placed directly on the skin.&#xD;
  &#xD;
        On the morning of day 2, a researcher will wake the participant at 07:00. Using a mouthpiece&#xD;
        (alike to a snorkel) and nose clip, expired air at rest will be collected for 20 minutes to&#xD;
        calculate how much energy is burnt at rest. Participants will also be asked to give a breath&#xD;
        sample into a small glass tube through a straw (this is related to a tracer method explained&#xD;
        below). Body mass will be measured again after the participant has an opportunity to use the&#xD;
        bathroom.&#xD;
  &#xD;
        Once settled back in bed, a trained member of staff will insert a cannula (small plastic&#xD;
        tube) into a vein on the back of the participant's hand or forearm. This will stay in place&#xD;
        for the remainder of the day and allows repeated blood samples to be taken throughout the&#xD;
        following tests. For participants with skeletal dysplasia, the genetic material found in&#xD;
        cells will be taken out of the first blood sample and later analysed to confirm a correct&#xD;
        diagnosis of achondroplasia. Participants will be asked to place the hand in a warm box set&#xD;
        at 55°C which helps blood flow and makes taking samples easier for the research team. All&#xD;
        participants will then be asked to complete a series of appetite questions, a portion&#xD;
        selection task, and blood pressure will be taken.&#xD;
  &#xD;
        When the hand is warm and initial appetite tasks are completed, participants will be provided&#xD;
        with a sugary drink and asked to finish it within 5 minutes. The drink will also contain a&#xD;
        sugar tracer which is stable and safe-to-consume. This allows the research team to assess how&#xD;
        the drink is being processed by the body in real time. For a few individuals from each&#xD;
        'subgroup' (achondroplasia, skeletal dysplasia, extremely large body size, and extremely&#xD;
        small body size), a different tracer called acetate will be added to the drink which will&#xD;
        help with some calculations of how the body processes the sugar. Blood samples (10 mL) will&#xD;
        be drawn from the cannula every 15 minutes for the first hour, and 30 minutes for the next&#xD;
        two hours. At these same intervals, the participant will be asked to blow into a small tube&#xD;
        using a straw to assess the appearance of the tracer on the breath (an indicator of how much&#xD;
        sugar is being burnt from the drink, as opposed to the body's sugar stores, hence the need&#xD;
        for a baseline sample). Participants will also be asked to complete the appetite questions&#xD;
        and portion selection task whenever a blood sample is drawn. At 60, 120 and 180 minutes, a&#xD;
        one 5-minute sample of air will be collected just as upon waking, and blood pressure will be&#xD;
        measured on the hour. In between samples the participant may also complete a series of&#xD;
        questionnaires regarding mental health (optional).&#xD;
  &#xD;
        At 11:00, participants will be presented with another appetite task and then a lunch meal&#xD;
        (pesto pasta with cheese, and a glass of orange juice) to consume within 20-minutes. A few&#xD;
        additional appetite questions will be asked pre- and post- meal consumption. The following 3&#xD;
        hours will be similar to before, with regular appetite scales to complete, and blood samples&#xD;
        drawn every 15 minutes for the first hour, and 30 minutes for the next two hours. At 60, 120&#xD;
        and 180 minutes, one 5-minute breath sample and a smaller tracer breath sample through the&#xD;
        straw will be collected, and blood pressure recorded.&#xD;
  &#xD;
        Participants will then be asked to complete a short treadmill test to calibrate the activity&#xD;
        monitor by wearing a heart rate monitor on a chest strap whilst walking. Five 3-minute&#xD;
        incremental stages will be calculated based on the participants 'normal' self-selected&#xD;
        walking speed. During the final minute of each stage, a one-minute breath sample will be&#xD;
        collected and heart rate recorded. A breath sample into a tracer collection tube will also be&#xD;
        obtained at the end of each exercise stage. Whilst on the treadmill, participants will be&#xD;
        asked to describe how difficult the exercise stages feel. If the fastest speed has not&#xD;
        exceeded 'hard' exercise, the researcher will ask if the participant feels able to complete a&#xD;
        final stage at a higher intensity (not exceeding a rating of perceived exertion of 15) to&#xD;
        assist calibration of the activity monitor. Within 30 seconds of finishing on the treadmill&#xD;
        one final blood sample will be drawn from the cannula before removing it.&#xD;
  &#xD;
        On leaving the lab, participants will be provided with an activity monitor, a motion watch, a&#xD;
        food diary (either on a mobile app or paper copy), and food and body weight scales. A small&#xD;
        device to continuously measure blood sugar levels will also be fitted to the back of the arm.&#xD;
        The device is inserted with a very small needle which is then removed, leaving only the patch&#xD;
        with a small probe in the arm. The research team will instruct participants on how to wear&#xD;
        the activity monitor on the chest and ask that participant wear this at all times other than&#xD;
        when swimming or bathing, and record food intake for 14-days. During this time, participants&#xD;
        will be asked to weigh themselves first thing in the morning and last thing at night, as well&#xD;
        as recording sleep times and quality.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 17, 2023</start_date>
    <completion_date type="Anticipated">September 28, 2035</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2025</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>Glucose incremental area under the curve during the oral glucose tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Difference in blood glucose incremental area under the curve between individuals with skeletal dysplasia, and extremely small and large body size.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Fasted blood glucose concentration</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasted blood insulin concentration</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin response to oral glucose tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of blood insulin after oral glucose tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-Peptide response to oral glucose tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of blood C-Peptide after oral glucose tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Regulatory hormone response to oral glucose tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of regulatory hormones e.g. ghrelin after oral glucose tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glycaemic response to mixed meal tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of blood glucose after mixed meal tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Insulin response to mixed meal tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of blood insulin after mixed meal tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-Peptide response to mixed meal tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of blood C-Peptide after mixed meal tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Regulatory hormone response to mixed meal tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Incremental area under the curve of regulatory hormones e.g. ghrelin after mixed meal tolerance test</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Resting metabolic rate</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Substrate oxidation during oral glucose tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Total fat and carbohydrate oxidation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Substrate oxidation during mixed meal tolerance test</measure>
      <time_frame>3 hours</time_frame>
      <description>Total fat and carbohydrate oxidation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Exogenous carbohydrate oxidation</measure>
      <time_frame>7 hours</time_frame>
      <description>Time course for whole-body exogenous carbohydrate using stable isotope methodology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasting muscle glycogen concentration</measure>
      <time_frame>Baseline</time_frame>
      <description>Difference between individuals with skeletal dysplasia, extremely small and large body morphology.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Non-oxidative glucose disposal</measure>
      <time_frame>7 hours</time_frame>
      <description>Difference in exogenous carbohydrate consumption and exogenous carbohydrate oxidation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Continuous interstitial glucose concentration</measure>
      <time_frame>10 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adipose tissue markers of insulin signalling</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adipose tissue markers of glucose metabolism</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skeletal muscle markers of insulin signalling</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skeletal muscle markers of glucose metabolism</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasted concentration of systemic adipokines (e.g., adiponectin, resistin, leptin etc.)</measure>
      <time_frame>Baseline</time_frame>
    </secondary_outcome>
    <other_outcome>
      <measure>Height</measure>
      <time_frame>Baseline</time_frame>
      <description>Metres</description>
    </other_outcome>
    <other_outcome>
      <measure>Body mass</measure>
      <time_frame>Baseline</time_frame>
      <description>Kilograms</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in body mass over 14 days of free-living monitoring</measure>
      <time_frame>14 days</time_frame>
      <description>Kilograms</description>
    </other_outcome>
    <other_outcome>
      <measure>Waist:Hip ratio</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Sagittal abdominal diameter</measure>
      <time_frame>Baseline</time_frame>
      <description>Centimeters</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood pressure</measure>
      <time_frame>6 hours</time_frame>
      <description>mmHg</description>
    </other_outcome>
    <other_outcome>
      <measure>Intracellular markers and signalling pathways related to carbohydrate metabolism in adipose tissue</measure>
      <time_frame>Baseline</time_frame>
      <description>Comparing adipose tissue between skeletal dysplasia, extremely small and large groups</description>
    </other_outcome>
    <other_outcome>
      <measure>Intracellular markers and signalling pathways related to carbohydrate metabolism in skeletal muscle</measure>
      <time_frame>Baseline</time_frame>
      <description>Comparing muscle tissue between skeletal dysplasia, extremely small and large groups</description>
    </other_outcome>
    <other_outcome>
      <measure>Full blood lipid profile</measure>
      <time_frame>7 hours</time_frame>
      <description>Blood analysed and compared between skeletal dysplasia, extremely small and large groups</description>
    </other_outcome>
    <other_outcome>
      <measure>Fasted markers of chronic low-grade inflammation</measure>
      <time_frame>Baseline</time_frame>
      <description>Blood analysed and compared between skeletal dysplasia, extremely small and large groups</description>
    </other_outcome>
    <other_outcome>
      <measure>FGFR protein expression and signalling pathway exploration</measure>
      <time_frame>Baseline</time_frame>
      <description>Muscle tissue analysed and compared between skeletal dysplasia, extremely small and large groups</description>
    </other_outcome>
    <other_outcome>
      <measure>24-hour protein oxidation</measure>
      <time_frame>24 hours</time_frame>
      <description>Grams per minute</description>
    </other_outcome>
    <other_outcome>
      <measure>Genotype- FGFR3 mutation (skeletal dysplasia group only)</measure>
      <time_frame>Baseline</time_frame>
      <description>Assessed from buffy coat layer</description>
    </other_outcome>
    <other_outcome>
      <measure>Panel of female sex hormones</measure>
      <time_frame>Baseline</time_frame>
      <description>To verify menstrual cycle phase</description>
    </other_outcome>
    <other_outcome>
      <measure>DEXA bone mineral density</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>DEXA fat mass</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>DEXA fat-free mass</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>pQCT - muscle cross-sectional area</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>pQCT - tissue density</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>pQCT - bone geometry</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Assessment of eating behaviour</measure>
      <time_frame>Baseline</time_frame>
      <description>The Three Factor Eating Questionnaire</description>
    </other_outcome>
    <other_outcome>
      <measure>Visual analogue scale appetite ratings</measure>
      <time_frame>6 hours</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Portion selection task</measure>
      <time_frame>6 hours</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Polysomnography profile</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Daily self-reported energy intake during free-living monitoring</measure>
      <time_frame>14 days</time_frame>
      <description>Daily self-reported energy intake using Nutritics Libro Application</description>
    </other_outcome>
    <other_outcome>
      <measure>Daily free-living physical activity energy expenditure</measure>
      <time_frame>14 days</time_frame>
      <description>Daily free-living physical activity measured by Actiheart monitor</description>
    </other_outcome>
    <other_outcome>
      <measure>Free-living sleep quality</measure>
      <time_frame>14 days</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Free-living sleep duration</measure>
      <time_frame>14 days</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Free-living light exposure</measure>
      <time_frame>14 days</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Diet induced thermogenesis</measure>
      <time_frame>14 days</time_frame>
      <description>Calculated from self-reported energy intake</description>
    </other_outcome>
    <other_outcome>
      <measure>Heart rate during exercise</measure>
      <time_frame>15 minutes</time_frame>
      <description>Beats per minute</description>
    </other_outcome>
    <other_outcome>
      <measure>Rate of perceived exertion during exercise</measure>
      <time_frame>15 minutes</time_frame>
      <description>BORG scale</description>
    </other_outcome>
    <other_outcome>
      <measure>Energy expenditure during exercise</measure>
      <time_frame>15 mins</time_frame>
      <description>Substrate oxidation during walking exercise</description>
    </other_outcome>
    <other_outcome>
      <measure>Mental health assessment</measure>
      <time_frame>Baseline</time_frame>
      <description>Validated questionnaires</description>
    </other_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">102</enrollment>
    <condition>Skeletal Dysplasia</condition>
    <arm_group>
      <arm_group_label>Individuals with extreme body size</arm_group_label>
      <description>Any individual with a form of skeletal dysplasia, or extremely small or large body size.</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Individuals with extreme body size or proportions.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 16 years or over&#xD;
  &#xD;
            -  Any diagnosed form of skeletal dysplasia (i.e., extreme proportionate or&#xD;
               disproportionate short stature)&#xD;
  &#xD;
            -  Individuals without skeletal dysplasia but presenting with extreme body morphology,&#xD;
               defined as: individuals with extreme large body morphology (males &gt;75 kg fat-free mass&#xD;
               and females &gt;57.25 kg fat-free mass), or males and females with extreme small body&#xD;
               morphology (&lt;47.4 kg fat-free mass).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Any reported condition, behaviour or reported use of substances which may pose undue&#xD;
               personal risk to the participant or introduce bias into the study, except for any&#xD;
               which are ubiquitous in society and so would be equally distributed between groups&#xD;
               and/or therefore relevant to generalisation (e.g., statins, caffeine, GLP-1 agonists).&#xD;
  &#xD;
            -  Females who are pregnant or lactating&#xD;
  &#xD;
            -  Individuals with a diagnosed history of eating disorders (e.g., anorexia)&#xD;
  &#xD;
            -  Individuals with known bleeding disorders (exclusion for biopsies only)&#xD;
  &#xD;
            -  Individuals with known allergy or intolerance to lidocaine&#xD;
  &#xD;
            -  Inability to read or speak English, or otherwise to consent to procedures&#xD;
  &#xD;
            -  Individuals who are not weight stable (i.e., &gt;3 kg change in body mass in past 3&#xD;
               months)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>16 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>James A Betts, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Bath</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lucy H Merrell, BSc</last_name>
      <phone>07890949764</phone>
      <email>lhm31@bath.ac.uk</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Bath</name>
        <address>
          <city>Bath</city>
          <zip>BA27AY</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lucy H Merrell, PhD</last_name>
        <phone>07890949764</phone>
        <email>lhm31@bath.ac.uk</email>
      </contact>
      <investigator>
        <last_name>James A Betts, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Lucy H Merrell, BSc</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jean-Philippe Walhin, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Javier T Gonzalez, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Francoise Koumanov, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jeffrey Lambert, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Peter J Rogers, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jeffrey M Brunstrom, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <link>
      <url>https://www.bath.ac.uk/campaigns/take-part-in-our-study-about-body-size-and-metabolic-health/</url>
      <description>University of Bath webpage</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Bath</investigator_affiliation>
      <investigator_full_name>James Betts</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Morphology</keyword>
    <keyword>Skeletal dysplasia</keyword>
    <keyword>Metabolism</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osteochondrodysplasias</mesh_term>
    </condition_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/NCT05991609
  org study id: 321662
  nct id: NCT05991609
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Researchers at the University of Bath are investigating the metabolism of individuals with
        extreme body size, including those with skeletal dysplasia (commonly known as dwarfism), to
        manage health risks such as heart disease. By better understanding how body size could change
        how the body processes food, or how being bigger or smaller may influence eating habits,
        healthy living guidelines to tackle issues such as obesity and overweight in these
        populations can be improved. With help from expertise in the psychology field, this research
        will also investigate whether the mental health of these individuals has been affected by
        their size. On the whole, this study will involve one 24-hour visit to a research laboratory
        at the University of Bath, followed by a 2-week monitoring period to capture 'normal'
        physical activity and eating routines.
  After signing informed consent to take part in the study, participants will be asked to
        complete a health entry criteria questionnaire, including a physical activity readiness
        questionnaire and Eating Disorder Examination Questionnaire, to confirm eligibility.
        Participants will also be required to complete a health questionnaire for administration of
        anaesthetic as part of the biopsy procedure. Individuals who are very small or very big
        (without skeletal dysplasia) will be asked to attend the laboratory for a pre-trial screening
        as an additional eligibility criterion. This will involve measuring height, body mass, and
        standing on a specialised scale (bioelectrical impedance scale) which estimates how much
        muscle and fat someone has. If it is suspected that the participant meets the stated fat-free
        mass criteria, a complete a full body Dual Energy X-ray Absorptiometry (DEXA) scan to assess
        body composition more accurately will be completed. This involves lying flat on a bed for ~7
        minutes and resting whilst the scan takes place. The research team will then inform the
        participant after analysing the scan results if they are eligible and can continue with the
        study.
  
        All participants deemed eligible who are able and willing to take part will be invited to
        attend the University of Bath Human Physiology Laboratory for the full trial.
  
        On day 1, prior to attending the University of Bath participants will be asked to eat a
        standardised diet of a cereal breakfast, and a supermarket purchased sandwich, drink and
        snack meal deal for lunch, with self-selected quantities. Participants will ideally be fasted
        for 4-5 hours before arrival (~17:00).
  
        Upon arrive at the University, individuals with skeletal dysplasia will also be asked to
        complete the health entry criteria questionnaire and physical activity readiness
        questionnaire to ensure eligibility. It is important that participants let the researchers
        know of any medical conditions or any change in circumstance since signing up. All
        information is strictly confidential.
  
        The research team will first take measurements of height, body mass, waist and hip
        circumference, abdomen diameter (distance from your front to back), sitting height and blood
        pressure. Early into the visit, participants will also be briefed on collecting urine into
        provided containers. Individuals with skeletal dysplasia will then have a Dual Energy X-ray
        Absorptiometry (DEXA) scan to assess body composition. All participants will also have a
        Peripheral Quantitative Computed Tomography (pQCT) scan which involves placing one leg into a
        round scanner to assess the tissues in your leg e.g., bone, muscle and fat (as if the image
        were a slice). The scan requires you to keep your leg still for ~10 minutes.
  
        Participants will then be asked to rest in a bed and relax. In a seated position,
        participants will complete a lung function test at rest which requires blowing into a
        specialised device through a mouthpiece. Following this, after lying down and being briefed
        on the procedure, a trained member of staff will take a fat tissue biopsy from the abdomen to
        analyse genes and proteins in the cells. The fat biopsy involves inserting a needle with
        suction just below the skin to extract the cells and will be performed under local
        anaesthetic. This procedure may cause a bruise for up to 7 days. Following on from this, a
        muscle biopsy will be taken from the quadriceps (large muscle on the front of the thigh) to
        again measure genes and proteins as well as signalling pathways involved in our metabolism.
        The needle is inserted just inside the muscle and 2/3 snips of tissue are collected. The
        research team will provide information and equipment for aftercare of the biopsy sites to
        prevent infection after participants leave the laboratory.
  
        Participants will then be provided with a hot meal for dinner. This will be a standard
        portion of Sainsbury's Love Your Veg! Lentil Cottage Pie (400 g, serves 1). Prior to turning
        the lights out at 22:00, participants will be fitted with sleep monitoring kit known as
        polysomnography. The equipment includes an abdominal and chest pressure sensing band, a nasal
        cannula and some sticky sensors placed directly on the skin.
  
        On the morning of day 2, a researcher will wake the participant at 07:00. Using a mouthpiece
        (alike to a snorkel) and nose clip, expired air at rest will be collected for 20 minutes to
        calculate how much energy is burnt at rest. Participants will also be asked to give a breath
        sample into a small glass tube through a straw (this is related to a tracer method explained
        below). Body mass will be measured again after the participant has an opportunity to use the
        bathroom.
  
        Once settled back in bed, a trained member of staff will insert a cannula (small plastic
        tube) into a vein on the back of the participant's hand or forearm. This will stay in place
        for the remainder of the day and allows repeated blood samples to be taken throughout the
        following tests. For participants with skeletal dysplasia, the genetic material found in
        cells will be taken out of the first blood sample and later analysed to confirm a correct
        diagnosis of achondroplasia. Participants will be asked to place the hand in a warm box set
        at 55°C which helps blood flow and makes taking samples easier for the research team. All
        participants will then be asked to complete a series of appetite questions, a portion
        selection task, and blood pressure will be taken.
  
        When the hand is warm and initial appetite tasks are completed, participants will be provided
        with a sugary drink and asked to finish it within 5 minutes. The drink will also contain a
        sugar tracer which is stable and safe-to-consume. This allows the research team to assess how
        the drink is being processed by the body in real time. For a few individuals from each
        'subgroup' (achondroplasia, skeletal dysplasia, extremely large body size, and extremely
        small body size), a different tracer called acetate will be added to the drink which will
        help with some calculations of how the body processes the sugar. Blood samples (10 mL) will
        be drawn from the cannula every 15 minutes for the first hour, and 30 minutes for the next
        two hours. At these same intervals, the participant will be asked to blow into a small tube
        using a straw to assess the appearance of the tracer on the breath (an indicator of how much
        sugar is being burnt from the drink, as opposed to the body's sugar stores, hence the need
        for a baseline sample). Participants will also be asked to complete the appetite questions
        and portion selection task whenever a blood sample is drawn. At 60, 120 and 180 minutes, a
        one 5-minute sample of air will be collected just as upon waking, and blood pressure will be
        measured on the hour. In between samples the participant may also complete a series of
        questionnaires regarding mental health (optional).
  
        At 11:00, participants will be presented with another appetite task and then a lunch meal
        (pesto pasta with cheese, and a glass of orange juice) to consume within 20-minutes. A few
        additional appetite questions will be asked pre- and post- meal consumption. The following 3
        hours will be similar to before, with regular appetite scales to complete, and blood samples
        drawn every 15 minutes for the first hour, and 30 minutes for the next two hours. At 60, 120
        and 180 minutes, one 5-minute breath sample and a smaller tracer breath sample through the
        straw will be collected, and blood pressure recorded.
  
        Participants will then be asked to complete a short treadmill test to calibrate the activity
        monitor by wearing a heart rate monitor on a chest strap whilst walking. Five 3-minute
        incremental stages will be calculated based on the participants 'normal' self-selected
        walking speed. During the final minute of each stage, a one-minute breath sample will be
        collected and heart rate recorded. A breath sample into a tracer collection tube will also be
        obtained at the end of each exercise stage. Whilst on the treadmill, participants will be
        asked to describe how difficult the exercise stages feel. If the fastest speed has not
        exceeded 'hard' exercise, the researcher will ask if the participant feels able to complete a
        final stage at a higher intensity (not exceeding a rating of perceived exertion of 15) to
        assist calibration of the activity monitor. Within 30 seconds of finishing on the treadmill
        one final blood sample will be drawn from the cannula before removing it.
  
        On leaving the lab, participants will be provided with an activity monitor, a motion watch, a
        food diary (either on a mobile app or paper copy), and food and body weight scales. A small
        device to continuously measure blood sugar levels will also be fitted to the back of the arm.
        The device is inserted with a very small needle which is then removed, leaving only the patch
        with a small probe in the arm. The research team will instruct participants on how to wear
        the activity monitor on the chest and ask that participant wear this at all times other than
        when swimming or bathing, and record food intake for 14-days. During this time, participants
        will be asked to weigh themselves first thing in the morning and last thing at night, as well
        as recording sleep times and quality.
  observational model: Cohort
  time perspective: Cross-Sectional
  measure: Glucose incremental area under the curve during the oral glucose tolerance test
  time frame: 3 hours
  description: Difference in blood glucose incremental area under the curve between individuals with skeletal dysplasia, and extremely small and large body size.
  measure: Fasted blood glucose concentration
  time frame: Baseline
  measure: Fasted blood insulin concentration
  time frame: Baseline
  measure: Insulin response to oral glucose tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of blood insulin after oral glucose tolerance test
  measure: C-Peptide response to oral glucose tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of blood C-Peptide after oral glucose tolerance test
  measure: Regulatory hormone response to oral glucose tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of regulatory hormones e.g. ghrelin after oral glucose tolerance test
  measure: Glycaemic response to mixed meal tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of blood glucose after mixed meal tolerance test
  measure: Insulin response to mixed meal tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of blood insulin after mixed meal tolerance test
  measure: C-Peptide response to mixed meal tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of blood C-Peptide after mixed meal tolerance test
  measure: Regulatory hormone response to mixed meal tolerance test
  time frame: 3 hours
  description: Incremental area under the curve of regulatory hormones e.g. ghrelin after mixed meal tolerance test
  measure: Resting metabolic rate
  time frame: Baseline
  measure: Substrate oxidation during oral glucose tolerance test
  time frame: 3 hours
  description: Total fat and carbohydrate oxidation
  measure: Substrate oxidation during mixed meal tolerance test
  time frame: 3 hours
  description: Total fat and carbohydrate oxidation
  measure: Exogenous carbohydrate oxidation
  time frame: 7 hours
  description: Time course for whole-body exogenous carbohydrate using stable isotope methodology
  measure: Fasting muscle glycogen concentration
  time frame: Baseline
  description: Difference between individuals with skeletal dysplasia, extremely small and large body morphology.
  measure: Non-oxidative glucose disposal
  time frame: 7 hours
  description: Difference in exogenous carbohydrate consumption and exogenous carbohydrate oxidation
  measure: Continuous interstitial glucose concentration
  time frame: 10 days
  measure: Adipose tissue markers of insulin signalling
  time frame: Baseline
  measure: Adipose tissue markers of glucose metabolism
  time frame: Baseline
  measure: Skeletal muscle markers of insulin signalling
  time frame: Baseline
  measure: Skeletal muscle markers of glucose metabolism
  time frame: Baseline
  measure: Fasted concentration of systemic adipokines (e.g., adiponectin, resistin, leptin etc.)
  time frame: Baseline
  measure: Height
  time frame: Baseline
  description: Metres
  measure: Body mass
  time frame: Baseline
  description: Kilograms
  measure: Change in body mass over 14 days of free-living monitoring
  time frame: 14 days
  description: Kilograms
  measure: Waist:Hip ratio
  time frame: Baseline
  measure: Sagittal abdominal diameter
  time frame: Baseline
  description: Centimeters
  measure: Blood pressure
  time frame: 6 hours
  description: mmHg
  measure: Intracellular markers and signalling pathways related to carbohydrate metabolism in adipose tissue
  time frame: Baseline
  description: Comparing adipose tissue between skeletal dysplasia, extremely small and large groups
  measure: Intracellular markers and signalling pathways related to carbohydrate metabolism in skeletal muscle
  time frame: Baseline
  description: Comparing muscle tissue between skeletal dysplasia, extremely small and large groups
  measure: Full blood lipid profile
  time frame: 7 hours
  description: Blood analysed and compared between skeletal dysplasia, extremely small and large groups
  measure: Fasted markers of chronic low-grade inflammation
  time frame: Baseline
  description: Blood analysed and compared between skeletal dysplasia, extremely small and large groups
  measure: FGFR protein expression and signalling pathway exploration
  time frame: Baseline
  description: Muscle tissue analysed and compared between skeletal dysplasia, extremely small and large groups
  measure: 24-hour protein oxidation
  time frame: 24 hours
  description: Grams per minute
  measure: Genotype- FGFR3 mutation (skeletal dysplasia group only)
  time frame: Baseline
  description: Assessed from buffy coat layer
  measure: Panel of female sex hormones
  time frame: Baseline
  description: To verify menstrual cycle phase
  measure: DEXA bone mineral density
  time frame: Baseline
  measure: DEXA fat mass
  time frame: Baseline
  measure: DEXA fat-free mass
  time frame: Baseline
  measure: pQCT - muscle cross-sectional area
  time frame: Baseline
  measure: pQCT - tissue density
  time frame: Baseline
  measure: pQCT - bone geometry
  time frame: Baseline
  measure: Assessment of eating behaviour
  time frame: Baseline
  description: The Three Factor Eating Questionnaire
  measure: Visual analogue scale appetite ratings
  time frame: 6 hours
  measure: Portion selection task
  time frame: 6 hours
  measure: Polysomnography profile
  time frame: Baseline
  measure: Daily self-reported energy intake during free-living monitoring
  time frame: 14 days
  description: Daily self-reported energy intake using Nutritics Libro Application
  measure: Daily free-living physical activity energy expenditure
  time frame: 14 days
  description: Daily free-living physical activity measured by Actiheart monitor
  measure: Free-living sleep quality
  time frame: 14 days
  measure: Free-living sleep duration
  time frame: 14 days
  measure: Free-living light exposure
  time frame: 14 days
  measure: Diet induced thermogenesis
  time frame: 14 days
  description: Calculated from self-reported energy intake
  measure: Heart rate during exercise
  time frame: 15 minutes
  description: Beats per minute
  measure: Rate of perceived exertion during exercise
  time frame: 15 minutes
  description: BORG scale
  measure: Energy expenditure during exercise
  time frame: 15 mins
  description: Substrate oxidation during walking exercise
  measure: Mental health assessment
  time frame: Baseline
  description: Validated questionnaires
  arm group label: Individuals with extreme body size
  description: Any individual with a form of skeletal dysplasia, or extremely small or large body size.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 16 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: James A Betts, PhD
  role: Principal Investigator
  affiliation: University of Bath
  last name: Lucy H Merrell, BSc
  phone: 07890949764
  email: lhm31@bath.ac.uk
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United Kingdom
  url: https://www.bath.ac.uk/campaigns/take-part-in-our-study-about-body-size-and-metabolic-health/
  description: University of Bath webpage
  responsible party type: Principal Investigator
  investigator affiliation: University of Bath
  investigator full name: James Betts
  investigator title: Professor
  mesh term: Osteochondrodysplasias
  sharing ipd: No