<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/NCT04477018</url>
  </required_header>
  <id_info>
    <org_study_id>9BN2</org_study_id>
    <nct_id>NCT04477018</nct_id>
  </id_info>
  <brief_title>16 Weeks' Dietary Supplementation With Iron and Iron + Vitamin C on Cerebral Blood Flow and Energy Expenditure in Women of Reproductive Age</brief_title>
  <official_title>16 Weeks' Dietary Supplementation With Iron and Iron + Vitamin C on Cerebral Blood Flow and Energy Expenditure in Women of Reproductive Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northumbria University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Northumbria University</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>
      Iron deficiency is the most prevalent nutritional deficiency worldwide with one in four&#xD;
      estimated to be affected by iron deficiency anaemia. Women of reproductive age are at&#xD;
      greatest risk for iron deficiency and anaemia due to iron losses during menstruation and&#xD;
      childbirth as well as the increased need for iron throughout pregnancy. However, iron&#xD;
      deficiency without anaemia is at least twice as common as iron deficiency anaemia with&#xD;
      females aged 11-49 at the biggest risk of all. Despite this, it is commonly left undiagnosed.&#xD;
      Those who are iron deficient non-anaemic can still suffer from the same common consequences&#xD;
      of iron deficiency anaemia; these include unexplained fatigue, mood changes and decreased&#xD;
      cognitive performance. It is postulated that for any cognitive and behavioural change to&#xD;
      occur, a complementary change in neural functioning is required. A recent cross-sectional&#xD;
      study has identified increases in cognitive demand to produce decrements in measures of&#xD;
      cognitive performance and increases in brain activity and metabolic measures; the magnitude&#xD;
      of such are evidenced to be directly related to iron status. However, such measures do not&#xD;
      provide an estimate of overall oxygen consumption that is specific to the brain in order to&#xD;
      be able to associate changes in cognitive performance and energy expenditure specifically to&#xD;
      the brain itself. The current study aims to investigate the parallel effects of iron&#xD;
      supplementation on cerebral haemodynamics and energy metabolism to determine the ability of&#xD;
      iron to modulate whole body energy metabolism and utilisation of metabolic substrates at rest&#xD;
      and during cognitive demand in a sample of non-anaemic iron deficient and iron sufficient&#xD;
      women of reproductive age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Each participant will be required to attend the laboratory on four occasions. The first is&#xD;
      comprised of a screening/training visit, which will take place in the afternoon for&#xD;
      approximately 2.5 hours. This will also be between days 21-28/ the week before onset of their&#xD;
      menstrual cycle. If they do not have menstrual bleeds then this appointment can be any&#xD;
      afternoon. This will comprise: briefing of requirements of the study; obtaining of informed&#xD;
      consent; confirmation of eligibility to take part, including collection of demographic data&#xD;
      and health screening, and training on the cognitive and mood measures. The training session&#xD;
      will follow standard operating procedures to decrease the chance of learning effects during&#xD;
      main trials. Extra training will be given where necessary.&#xD;
&#xD;
      Participants will be required to complete questionnaires based upon food frequency, caffeine&#xD;
      consumption and to estimate the number of hours of exercise completed on a weekly basis. A&#xD;
      menstrual cycle questionnaire will also be completed to estimate menstrual blood loss and so&#xD;
      that participants attend their testing visit during days 7-14 of their cycle. If participants&#xD;
      do not have a menstrual cycle due to contraceptive methods, then appointments will be&#xD;
      approximately two weeks apart. A finger-prick and venous blood sample will be collected from&#xD;
      participants, which will be analysed for iron status. Those whose haemoglobin levels are&#xD;
      &lt;120g/L will be advised to seek advice from their GP. Participants who fell into the iron&#xD;
      status category of iron sufficient (haemoglobin ≥120 g/L and serum ferritin &gt; 20 µg/L) or&#xD;
      non-anaemic iron deficient (haemoglobin ≥120 g/L and serum ferritin ≤ 20 µg/L) will be&#xD;
      informed of their eligibility for the intervention study by email or phone between the&#xD;
      initial visit and their next. This will include the option to enrol in an additional&#xD;
      assessment of neuroimaging and energy metabolism.&#xD;
&#xD;
      For the testing visit, participants will be asked to fast for 12 hours prior to the visit,&#xD;
      avoiding intake of all food and drink with the exception of water. They will also be asked to&#xD;
      avoid alcohol and refrain from intake of 'over the counter' medication for 24 hours.&#xD;
      Participants will arrive at the laboratory at a designated time in the morning. The following&#xD;
      procedures will take place prior to cognitive and mood testing:&#xD;
&#xD;
      Review of continued conformity to eligibility criteria Adverse event and concomitant&#xD;
      medication assessment Ensure that participant is in good health&#xD;
&#xD;
      Participants will then complete the baseline cognitive and mood assessments. Following this,&#xD;
      participants are informed of their iron status and will be briefed regarding the requirements&#xD;
      of the intervention study and additional assessment. Following this, informed consent will be&#xD;
      obtained prior to starting the additional assessment. Participants will have a frequency&#xD;
      domain near-infrared spectroscopy headband attached to the forehead to measure cerebral blood&#xD;
      flow at rest for five minutes. Following this, participants will instead have a continuous&#xD;
      wave near-infrared spectroscopy headband attached to the forehead to measure cerebral blood&#xD;
      flow, and a face mask fitted to measure expired air. Participants will have another five&#xD;
      minute rest before completing an additional battery of cognitive tasks for approximately&#xD;
      35-40 minutes. Once complete, participants will be randomised to one of three treatments and&#xD;
      be provided with a treatment diary to log treatment consumption and any adverse events&#xD;
      experienced.&#xD;
&#xD;
      Participants will return to the laboratory after 8 weeks to exchange treatment bottles and&#xD;
      diaries in order to check compliance.&#xD;
&#xD;
      Participants will finally return to the laboratory after a further 8 weeks (16 weeks total).&#xD;
      The same procedures will take place prior to cognitive and mood testing as completed at the&#xD;
      baseline testing visit, with the addition of finger prick and venous blood sample and weight&#xD;
      measurement. Participants will then complete the same cognitive, mood and neuroimaging and&#xD;
      energy metabolism assessments as completed during the baseline testing visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 11, 2017</start_date>
  <completion_date type="Actual">June 8, 2019</completion_date>
  <primary_completion_date type="Actual">June 8, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will receive either iron and vitamin C, iron alone or placebo for a period of 16 weeks to consume daily</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral Blood Flow</measure>
    <time_frame>16 weeks</time_frame>
    <description>Near Infrared Spectroscopy outcomes for cerebral blood flow measurement at rest and during cognitive demand</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serial Subtraction Performance</measure>
    <time_frame>16 weeks</time_frame>
    <description>Performance on serial subtractions (3s and 7s) will be assessed as total responses and total errors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rapid Visual Information Processing</measure>
    <time_frame>16 weeks</time_frame>
    <description>Performance is assessed as accuracy (%), correct reaction time (msec) and false alarms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective alertness</measure>
    <time_frame>16 weeks</time_frame>
    <description>Subjective alertness will be derived from an Alertness visual analogue scale presented following cognitive task performance. Scores range from 0 to 100. Higher scores are indicative of greater feelings of alertness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective fatigue</measure>
    <time_frame>16 weeks</time_frame>
    <description>Subjective mental fatigue will be derived from a Mental Fatigue visual analogue scale presented following cognitive task performance. Scores range from 0 to 100. Higher scores are indicative of greater feelings of mental fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat Oxidation</measure>
    <time_frame>16 weeks</time_frame>
    <description>Fat oxidation will be assessed through indirect calorimetry at rest and during cognitive demand</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carbohydrate Oxidation</measure>
    <time_frame>16 weeks</time_frame>
    <description>Carbohydrate oxidation will be assessed through indirect calorimetry at rest and during cognitive demand</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory Energy Ratio</measure>
    <time_frame>16 weeks</time_frame>
    <description>Respiratory energy ration will be assessed through indirect calorimetry at rest and during cognitive demand</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Energy Expenditure</measure>
    <time_frame>16 weeks</time_frame>
    <description>Total energy expenditure will be assessed through indirect calorimetry at rest and during cognitive demand</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Iron</condition>
  <condition>Cerebral Blood Flow</condition>
  <condition>Energy Metabolism</condition>
  <condition>Cognitive Function</condition>
  <arm_group>
    <arm_group_label>Iron and Vitamin C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>28 mg iron bis-glycinate chelate and 240 mg vitamin C</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Iron</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>28 mg iron bis-glycinate chelate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matched placebo tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Iron bis-glycinate chelate and vitamin C</intervention_name>
    <description>28 mg iron; 240 mg vitamin C</description>
    <arm_group_label>Iron and Vitamin C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Iron bis-glycinate chelate</intervention_name>
    <description>28 mg iron only</description>
    <arm_group_label>Iron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Aged 18-49 (inclusive)&#xD;
&#xD;
          -  Have a BMI of between 18.5-40&#xD;
&#xD;
          -  Have an English bank account (required for payment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Aged under 18 or above 49 years&#xD;
&#xD;
          -  BMI lower than 18.5 or higher than 40&#xD;
&#xD;
          -  Pre-existing medical condition/illness with some exceptions - please check with&#xD;
             researcher&#xD;
&#xD;
          -  Blood disorders (including anaemia) or any known active infections&#xD;
&#xD;
          -  Current or past breast cancer diagnosis and/or mastectomy&#xD;
&#xD;
          -  Smoking or use of any nicotine replacement products e.g. vaping, gum, patches&#xD;
&#xD;
          -  Pregnant, trying to get pregnant or breast feeding&#xD;
&#xD;
          -  Currently taking any prescription medication with some exceptions - please check with&#xD;
             researcher&#xD;
&#xD;
          -  Food allergies/sensitivities relevant to the study&#xD;
&#xD;
          -  Regular use of dietary/herbal supplements within the last month (defined as more than&#xD;
             3 consecutive days or 4 days in total)&#xD;
&#xD;
          -  Use of iron supplements within the past 4 months&#xD;
&#xD;
          -  Have donated more than 300ml of blood in the past 3 months&#xD;
&#xD;
          -  Have haemoglobin levels below 120g/L&#xD;
&#xD;
          -  History of significant head trauma or suffer from frequent migraines that require&#xD;
             medication (more than or equal to one per month)&#xD;
&#xD;
          -  Learning difficulties, dyslexia, or colour blindness&#xD;
&#xD;
          -  Visual impairment that cannot be corrected with glasses or contact lenses&#xD;
&#xD;
          -  Currently taking part in any other clinical or nutritional intervention studies or&#xD;
             have in the past 4 weeks&#xD;
&#xD;
          -  Any health condition that would prevent fulfilment of the study requirements&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Must be female at birth</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Brain, Performance &amp; Nutrition Research Centre, Northumbria University</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <zip>NE1 8ST</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 15, 2020</last_update_submitted>
  <last_update_submitted_qc>July 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Iron supplementation</keyword>
  <keyword>Cerebral blood flow</keyword>
  <keyword>Near infrared spectroscopy</keyword>
  <keyword>Indirect calorimetry</keyword>
  <keyword>Energy metabolism</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron</mesh_term>
    <mesh_term>Chelating Agents</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04477018
org study id: 9BN2
nct id: NCT04477018
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Iron deficiency is the most prevalent nutritional deficiency worldwide with one in four
      estimated to be affected by iron deficiency anaemia. Women of reproductive age are at
      greatest risk for iron deficiency and anaemia due to iron losses during menstruation and
      childbirth as well as the increased need for iron throughout pregnancy. However, iron
      deficiency without anaemia is at least twice as common as iron deficiency anaemia with
      females aged 11-49 at the biggest risk of all. Despite this, it is commonly left undiagnosed.
      Those who are iron deficient non-anaemic can still suffer from the same common consequences
      of iron deficiency anaemia; these include unexplained fatigue, mood changes and decreased
      cognitive performance. It is postulated that for any cognitive and behavioural change to
      occur, a complementary change in neural functioning is required. A recent cross-sectional
      study has identified increases in cognitive demand to produce decrements in measures of
      cognitive performance and increases in brain activity and metabolic measures; the magnitude
      of such are evidenced to be directly related to iron status. However, such measures do not
      provide an estimate of overall oxygen consumption that is specific to the brain in order to
      be able to associate changes in cognitive performance and energy expenditure specifically to
      the brain itself. The current study aims to investigate the parallel effects of iron
      supplementation on cerebral haemodynamics and energy metabolism to determine the ability of
      iron to modulate whole body energy metabolism and utilisation of metabolic substrates at rest
      and during cognitive demand in a sample of non-anaemic iron deficient and iron sufficient
      women of reproductive age.
Each participant will be required to attend the laboratory on four occasions. The first is
      comprised of a screening/training visit, which will take place in the afternoon for
      approximately 2.5 hours. This will also be between days 21-28/ the week before onset of their
      menstrual cycle. If they do not have menstrual bleeds then this appointment can be any
      afternoon. This will comprise: briefing of requirements of the study; obtaining of informed
      consent; confirmation of eligibility to take part, including collection of demographic data
      and health screening, and training on the cognitive and mood measures. The training session
      will follow standard operating procedures to decrease the chance of learning effects during
      main trials. Extra training will be given where necessary.

      Participants will be required to complete questionnaires based upon food frequency, caffeine
      consumption and to estimate the number of hours of exercise completed on a weekly basis. A
      menstrual cycle questionnaire will also be completed to estimate menstrual blood loss and so
      that participants attend their testing visit during days 7-14 of their cycle. If participants
      do not have a menstrual cycle due to contraceptive methods, then appointments will be
      approximately two weeks apart. A finger-prick and venous blood sample will be collected from
      participants, which will be analysed for iron status. Those whose haemoglobin levels are
      <120g/L will be advised to seek advice from their GP. Participants who fell into the iron
      status category of iron sufficient (haemoglobin ≥120 g/L and serum ferritin > 20 µg/L) or
      non-anaemic iron deficient (haemoglobin ≥120 g/L and serum ferritin ≤ 20 µg/L) will be
      informed of their eligibility for the intervention study by email or phone between the
      initial visit and their next. This will include the option to enrol in an additional
      assessment of neuroimaging and energy metabolism.

      For the testing visit, participants will be asked to fast for 12 hours prior to the visit,
      avoiding intake of all food and drink with the exception of water. They will also be asked to
      avoid alcohol and refrain from intake of 'over the counter' medication for 24 hours.
      Participants will arrive at the laboratory at a designated time in the morning. The following
      procedures will take place prior to cognitive and mood testing:

      Review of continued conformity to eligibility criteria Adverse event and concomitant
      medication assessment Ensure that participant is in good health

      Participants will then complete the baseline cognitive and mood assessments. Following this,
      participants are informed of their iron status and will be briefed regarding the requirements
      of the intervention study and additional assessment. Following this, informed consent will be
      obtained prior to starting the additional assessment. Participants will have a frequency
      domain near-infrared spectroscopy headband attached to the forehead to measure cerebral blood
      flow at rest for five minutes. Following this, participants will instead have a continuous
      wave near-infrared spectroscopy headband attached to the forehead to measure cerebral blood
      flow, and a face mask fitted to measure expired air. Participants will have another five
      minute rest before completing an additional battery of cognitive tasks for approximately
      35-40 minutes. Once complete, participants will be randomised to one of three treatments and
      be provided with a treatment diary to log treatment consumption and any adverse events
      experienced.

      Participants will return to the laboratory after 8 weeks to exchange treatment bottles and
      diaries in order to check compliance.

      Participants will finally return to the laboratory after a further 8 weeks (16 weeks total).
      The same procedures will take place prior to cognitive and mood testing as completed at the
      baseline testing visit, with the addition of finger prick and venous blood sample and weight
      measurement. Participants will then complete the same cognitive, mood and neuroimaging and
      energy metabolism assessments as completed during the baseline testing visit.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will receive either iron and vitamin C, iron alone or placebo for a period of 16 weeks to consume daily
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Cerebral Blood Flow
time frame: 16 weeks
description: Near Infrared Spectroscopy outcomes for cerebral blood flow measurement at rest and during cognitive demand
measure: Serial Subtraction Performance
time frame: 16 weeks
description: Performance on serial subtractions (3s and 7s) will be assessed as total responses and total errors
measure: Rapid Visual Information Processing
time frame: 16 weeks
description: Performance is assessed as accuracy (%), correct reaction time (msec) and false alarms
measure: Subjective alertness
time frame: 16 weeks
description: Subjective alertness will be derived from an Alertness visual analogue scale presented following cognitive task performance. Scores range from 0 to 100. Higher scores are indicative of greater feelings of alertness.
measure: Subjective fatigue
time frame: 16 weeks
description: Subjective mental fatigue will be derived from a Mental Fatigue visual analogue scale presented following cognitive task performance. Scores range from 0 to 100. Higher scores are indicative of greater feelings of mental fatigue.
measure: Fat Oxidation
time frame: 16 weeks
description: Fat oxidation will be assessed through indirect calorimetry at rest and during cognitive demand
measure: Carbohydrate Oxidation
time frame: 16 weeks
description: Carbohydrate oxidation will be assessed through indirect calorimetry at rest and during cognitive demand
measure: Respiratory Energy Ratio
time frame: 16 weeks
description: Respiratory energy ration will be assessed through indirect calorimetry at rest and during cognitive demand
measure: Total Energy Expenditure
time frame: 16 weeks
description: Total energy expenditure will be assessed through indirect calorimetry at rest and during cognitive demand
arm group label: Iron and Vitamin C
arm group type: Experimental
description: 28 mg iron bis-glycinate chelate and 240 mg vitamin C
arm group label: Iron
arm group type: Active Comparator
description: 28 mg iron bis-glycinate chelate
arm group label: Placebo
arm group type: Placebo Comparator
description: Matched placebo tablets
intervention type: Dietary Supplement
intervention name: Iron bis-glycinate chelate and vitamin C
description: 28 mg iron; 240 mg vitamin C
arm group label: Iron and Vitamin C
intervention type: Dietary Supplement
intervention name: Iron bis-glycinate chelate
description: 28 mg iron only
arm group label: Iron
intervention type: Dietary Supplement
intervention name: Placebo
description: Matched placebo
arm group label: Placebo
criteria: 
gender: Female
gender based: Yes
gender description: Must be female at birth
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Iron
mesh term: Chelating Agents