<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/NCT03270527</url>
  </required_header>
  <id_info>
    <org_study_id>RN0307A</org_study_id>
    <nct_id>NCT03270527</nct_id>
  </id_info>
  <brief_title>RISSCI-1 Blood Cholesterol Response Study</brief_title>
  <acronym>RISSCI-1</acronym>
  <official_title>Reading Imperial Surrey Saturated Fat Cholesterol Intervention (RISSCI) Study. RISSCI-1 Blood Cholesterol Response Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Surrey</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Reading</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Surrey</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Raised blood cholesterol (also referred to as blood LDL-cholesterol) is a major risk factor&#xD;
      for developing heart disease. Dietary saturated fat is recognised as the main dietary&#xD;
      component responsible for raising blood LDL-cholesterol, and reducing its intake has been the&#xD;
      mainstay of dietary guidelines for the prevention of heart disease for over 30 years.&#xD;
      However, there is very little evidence for a direct link between the intake of saturated fat&#xD;
      and risk of dying from heart disease. One explanation for this, is that the link between&#xD;
      saturated fat intake and heart disease is not a direct one, but relies heavily on the ability&#xD;
      of saturated fat to raise blood LDL-cholesterol levels. This LDL cholesterol-raising effect&#xD;
      of saturated fat is complex, and highly variable between individuals because of differences&#xD;
      in the metabolism of dietary fat and cholesterol between people. The main aim of this study&#xD;
      is to measure the amount of variation in blood LDL-cholesterol in healthy volunteers at the&#xD;
      Universities of Surrey and Reading in response to lowering the amount of saturated fat in the&#xD;
      diet to the level recommended by the government for the prevention of heart disease. This&#xD;
      collaborative project between the Universities of Reading, Surrey and Imperial ('RISSCI-1'&#xD;
      Blood Cholesterol Response Study') will permit identification of two subgroups of men who&#xD;
      show either a high or low LDL-cholesterol response to a reduction in dietary saturated&#xD;
      intake. These two groups of participants will be provided with an opportunity to participate&#xD;
      in a similar follow-up study ('RISSCI-2') that will also take place at the University of&#xD;
      Surrey and Reading. In this follow-up study, the participants will be asked to repeat a&#xD;
      similar study protocol as for RISSCI-1, but undergo more detailed measurements to investigate&#xD;
      the metabolic and genetic origins of how saturated fat is metabolised in the body and&#xD;
      influences blood LDL-cholesterol (LDL-C).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The LDL cholesterol-raising effect of saturated fatty acids (SFA) is complex, and highly&#xD;
      variable between individuals because of differences in the metabolism of dietary fat and&#xD;
      blood cholesterol between people. While these differences in metabolism make it difficult to&#xD;
      study how dietary SFA influences LDL-cholesterol in large numbers of people, they can be&#xD;
      measured in the laboratory and used as biological markers to distinguish between people who&#xD;
      respond well from those who will respond less well to moderate-fat diets, which are lower in&#xD;
      SFA.&#xD;
&#xD;
      The main aim of this study is to measure the amount of variation in blood LDL-cholesterol in&#xD;
      healthy male volunteers in response to the replacement of SFA with unsaturated fats, and to&#xD;
      select LDL-C responders from non-responders for a subsequent metabolic study ('RISSC-2').&#xD;
      Estimate of statistical power and sample size for 'RISSCI-1': A decrease of 0.16 mmol/L (SD&#xD;
      0.54) in our primary outcome of fasting plasma LDL-C between the high- and low-SFA diets, as&#xD;
      observed in a previous randomly controlled trial, will require a sample size of 92&#xD;
      participants, at 80% power and 5% significance level. An estimated attrition rate of 15% will&#xD;
      increase this sample size to 106 participants. To recruit this sample of participants, we&#xD;
      anticipate having to screen 150 volunteers (75 at each site).&#xD;
&#xD;
      Specific objectives:&#xD;
&#xD;
        1. Undertake a dietary intervention study to examine the effects of two, 4 week diets that&#xD;
           differ in their composition of fatty acids. The first diet ('Diet 1') will contain ~18%&#xD;
           of its total energy as saturated fatty acids (SFA), while the second diet ('Diet 2')&#xD;
           will contain ~10% of its total energy as SFA. Blood, urine and stool samples taken at&#xD;
           the beginning (week 0) and end of Diet 1 (week 4), and end of Diet 2 (week 8), will be&#xD;
           analysed to measure blood LDL-cholesterol and other relevant blood, urine and faecal&#xD;
           metabolites. The white blood cell buffy coat will also be isolated from the blood&#xD;
           samples collected at the baseline visit to enable genotyping of relevant genes involved&#xD;
           in the absorption and metabolism of dietary fat.&#xD;
&#xD;
        2. To examine the data for evidence of associations between the changes in blood LDL-&#xD;
           cholesterol, and the physical and biochemical characteristics of the participants as&#xD;
           possible determinants of the variation in serum cholesterol response. This will include&#xD;
           measurement of a common genetic polymorphism in APOLIPOPROTEIN E, as an established&#xD;
           determinant of variation in blood cholesterol in response to dietary SFA.&#xD;
&#xD;
        3. To identify two subgroups of individuals whose blood LDL-cholesterol either responds&#xD;
           ('Responders') or show little or no response ('Non-responders') on changing from Diet 1&#xD;
           to Diet 2, for participation in the follow-up study ('RISSCI-2'), which will be&#xD;
           conducted at the Universities of Surrey, Reading and Imperial College London. In this&#xD;
           follow-up study, the participants will be asked to repeat a similar study protocol as&#xD;
           for RISSCI-1, and undergo more detailed measurements to determine how saturated fat is&#xD;
           metabolised in the body.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      In accordance with the variation in blood LDL-cholesterol response, that many studies have&#xD;
      reported previously following substitution of dietary saturated with unsaturated fats, the&#xD;
      investigators hypothesise that consuming Diet 1 (a high saturated fat diet) for 4 weeks&#xD;
      followed by diet 2 (a low saturated fat/high unsaturated fat diet) for a further 4 weeks,&#xD;
      will: 1) produce a variable distribution of responses in LDL-cholesterol that will enable the&#xD;
      study of associations between the participants' baseline characteristics as possible&#xD;
      determinants of the observed variation in blood LDL-cholesterol response, and 2) identify two&#xD;
      distinct subgroups of individuals who either respond or show little or no response in their&#xD;
      blood LDL- cholesterol. These distinct groups will be defined by the top and bottom ~10% of&#xD;
      change in the concentration of blood LDL-cholesterol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in fasting total cholesterol (consisting of LDL-cholesterol and HDL) concentrations</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fasting triacylglycerol</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL immune functions</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL anti-inflammatory and anti-oxidant (PON-1) properties</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL capacity to promote cholesterol efflux (ex-vivo)</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting insulin, glucose</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adhesion molecules, markers of vascular function</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory markers &amp; adipokines</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LDL-R gene expression</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other relevant genes involved in the absorption and metabolism of dietary fat</measure>
    <time_frame>Baseline</time_frame>
    <description>Polymorphic genes with potential influence on the serum LDL response to dietary saturated fat, e.g.: ATP-binding cassette proteins (cholesterol efflux proteins) ABCG5 (e.g. C1950G) ABCG8 (e.g. D19H, C1895T), functional polymorphisms in the farnesoid X receptor (FXR) and bile acid transporters (e.g. solute carrier organics anion 1B1). Fatty acid desaturases (FADS1 and FADS2). The patatin-like phospholipase domain-containing protein (PNPLA3) (e.g. rs738409 C/G), eNOS. Lipid/cholesterol homeostasis: serum apolipoprotein genes: APOE (ε2,ε3,ε4 e.g. rs429358 and rs7412), APOA-I (e.g. -75G/A), APOA4 (e.g. 360-2), APOA5 (e.g. -113/T&amp;gt:c), APOCIII, APOB (e.g. -516C/T). Lipase genes: (e.g. LPL, HL, MGLL). Lipoprotein receptor genes (e.g. pvu11 in the LDL receptor), lipid transfer proteins (e.g. CETP e.g Taq1B, MTP), and other polymorphic genes related to the absorption and metabolism of dietary fat and regulation of lipid/cholesterol homeostasis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolomic analysis for the determination of the low molecular weight metabolite profiles in the biological fluids</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
    <description>Analyses conducted by Imperial College London</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in faecal bacterial population</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
    <description>BMI will also be calculated (kg/ height in m^2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat mass</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat free mass</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist circumference</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hip circumference</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting vascular stiffness</measure>
    <time_frame>baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)</time_frame>
    <description>Measured via pulse wave assessment using the Mobil-O-graph device.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Genotyping for apolipoprotein E to determine the impact of this genotype on changes in the primary and secondary outcome measurements in response to dietary fat intake</measure>
    <time_frame>Baseline</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">109</enrollment>
  <condition>Lipids</condition>
  <condition>Lipid Metabolism</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>High SFA diet to low SFA diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo, sequentially, a high SFA diet (Diet 1) followed by a low SFA diet (Diet 2) for 4 weeks each. Study visits will occur before and after each dietary intervention period. To comply with current UK dietary recommendations, Diets 1 and 2 will both contain ~35% energy from total fat. These diets will be consumed within the homes of free-living participants, by the substitution of ~40g of habitual fat, with either SFA-rich or mono/poly-unsaturated fatty acid-rich (MUFA/PUFA) cooking oils, spreads and snack foods, while maintaining their habitual diet (consistent intake of protein and carbohydrates, including dietary fibre). This will be achieved using a dietary exchange model developed and peer-reviewed for a previous dietary intervention study ('DIVAS') at the University of Reading, U.K.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High SFA diet (Diet 1)</intervention_name>
    <description>'Diet 1' will contain ~18% of its total energy as SFA .</description>
    <arm_group_label>High SFA diet to low SFA diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low SFA diet (Diet 2)</intervention_name>
    <description>'Diet 2' will contain ~10% of its total energy as SFA. The SFA-replacement fats will be mixture of PUFA/MUFA.</description>
    <arm_group_label>High SFA diet to low SFA diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI of 19-32 kg/m2&#xD;
&#xD;
          -  Fasting serum total cholesterol &lt; 7.5 mmol/l and triacylglycerol &lt; 2.3 mmol/l&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Medical history of myocardial ischemia or stroke in the past 12 months;&#xD;
&#xD;
          -  Diabetes (defined as fasting glucose &gt; 7.0 mmol/l) or other endocrine disorders;&#xD;
             kidney, liver, pancreas or gastrointestinal disorders&#xD;
&#xD;
          -  Hypertension (blood pressure &gt; 140/90 mmHg),&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Medication for hyperlipidaemia (e.g. statins), hypertension, inflammation or&#xD;
             prescribed antibiotics within the last three months&#xD;
&#xD;
          -  Drinking in excess of 14 units of alcohol per week,&#xD;
&#xD;
          -  Anaemia (&lt;130 g/L haemoglobin), or planning on a weight-reducing regime&#xD;
&#xD;
          -  Taking any dietary supplements known to influence lipids/gut microbiota (eg. plant&#xD;
             stanols, fish oil, phytochemicals, natural laxatives, probiotics and prebiotics)&#xD;
&#xD;
          -  Any other unusual medical history or diet and lifestyle habits or practices that would&#xD;
             preclude volunteers from participating in a dietary intervention and metabolic study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce Griffin, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Surrey</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Lovegrove, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Reading</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Food and Nutritional Sciences, University of Reading</name>
      <address>
        <city>Reading</city>
        <state>Berkshire</state>
        <zip>RG6 6AP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Nutritional Sciences, University of Surrey</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <zip>GU2 7WG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Vafeiadou K, Weech M, Altowaijri H, Todd S, Yaqoob P, Jackson KG, Lovegrove JA. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. Am J Clin Nutr. 2015 Jul;102(1):40-8. doi: 10.3945/ajcn.114.097089. Epub 2015 May 27.</citation>
    <PMID>26016869</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>October 15, 2021</last_update_submitted>
  <last_update_submitted_qc>October 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Surrey</investigator_affiliation>
    <investigator_full_name>Bruce A. Griffin</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Dietary fat modification</keyword>
  <keyword>Lipids</keyword>
  <keyword>LDL cholesterol</keyword>
  <keyword>Dietary fatty acids</keyword>
  <keyword>Saturated fat</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03270527/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03270527
org study id: RN0307A
nct id: NCT03270527
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Raised blood cholesterol (also referred to as blood LDL-cholesterol) is a major risk factor
      for developing heart disease. Dietary saturated fat is recognised as the main dietary
      component responsible for raising blood LDL-cholesterol, and reducing its intake has been the
      mainstay of dietary guidelines for the prevention of heart disease for over 30 years.
      However, there is very little evidence for a direct link between the intake of saturated fat
      and risk of dying from heart disease. One explanation for this, is that the link between
      saturated fat intake and heart disease is not a direct one, but relies heavily on the ability
      of saturated fat to raise blood LDL-cholesterol levels. This LDL cholesterol-raising effect
      of saturated fat is complex, and highly variable between individuals because of differences
      in the metabolism of dietary fat and cholesterol between people. The main aim of this study
      is to measure the amount of variation in blood LDL-cholesterol in healthy volunteers at the
      Universities of Surrey and Reading in response to lowering the amount of saturated fat in the
      diet to the level recommended by the government for the prevention of heart disease. This
      collaborative project between the Universities of Reading, Surrey and Imperial ('RISSCI-1'
      Blood Cholesterol Response Study') will permit identification of two subgroups of men who
      show either a high or low LDL-cholesterol response to a reduction in dietary saturated
      intake. These two groups of participants will be provided with an opportunity to participate
      in a similar follow-up study ('RISSCI-2') that will also take place at the University of
      Surrey and Reading. In this follow-up study, the participants will be asked to repeat a
      similar study protocol as for RISSCI-1, but undergo more detailed measurements to investigate
      the metabolic and genetic origins of how saturated fat is metabolised in the body and
      influences blood LDL-cholesterol (LDL-C).
The LDL cholesterol-raising effect of saturated fatty acids (SFA) is complex, and highly
      variable between individuals because of differences in the metabolism of dietary fat and
      blood cholesterol between people. While these differences in metabolism make it difficult to
      study how dietary SFA influences LDL-cholesterol in large numbers of people, they can be
      measured in the laboratory and used as biological markers to distinguish between people who
      respond well from those who will respond less well to moderate-fat diets, which are lower in
      SFA.

      The main aim of this study is to measure the amount of variation in blood LDL-cholesterol in
      healthy male volunteers in response to the replacement of SFA with unsaturated fats, and to
      select LDL-C responders from non-responders for a subsequent metabolic study ('RISSC-2').
      Estimate of statistical power and sample size for 'RISSCI-1': A decrease of 0.16 mmol/L (SD
      0.54) in our primary outcome of fasting plasma LDL-C between the high- and low-SFA diets, as
      observed in a previous randomly controlled trial, will require a sample size of 92
      participants, at 80% power and 5% significance level. An estimated attrition rate of 15% will
      increase this sample size to 106 participants. To recruit this sample of participants, we
      anticipate having to screen 150 volunteers (75 at each site).

      Specific objectives:

        1. Undertake a dietary intervention study to examine the effects of two, 4 week diets that
           differ in their composition of fatty acids. The first diet ('Diet 1') will contain ~18%
           of its total energy as saturated fatty acids (SFA), while the second diet ('Diet 2')
           will contain ~10% of its total energy as SFA. Blood, urine and stool samples taken at
           the beginning (week 0) and end of Diet 1 (week 4), and end of Diet 2 (week 8), will be
           analysed to measure blood LDL-cholesterol and other relevant blood, urine and faecal
           metabolites. The white blood cell buffy coat will also be isolated from the blood
           samples collected at the baseline visit to enable genotyping of relevant genes involved
           in the absorption and metabolism of dietary fat.

        2. To examine the data for evidence of associations between the changes in blood LDL-
           cholesterol, and the physical and biochemical characteristics of the participants as
           possible determinants of the variation in serum cholesterol response. This will include
           measurement of a common genetic polymorphism in APOLIPOPROTEIN E, as an established
           determinant of variation in blood cholesterol in response to dietary SFA.

        3. To identify two subgroups of individuals whose blood LDL-cholesterol either responds
           ('Responders') or show little or no response ('Non-responders') on changing from Diet 1
           to Diet 2, for participation in the follow-up study ('RISSCI-2'), which will be
           conducted at the Universities of Surrey, Reading and Imperial College London. In this
           follow-up study, the participants will be asked to repeat a similar study protocol as
           for RISSCI-1, and undergo more detailed measurements to determine how saturated fat is
           metabolised in the body.

      Hypothesis:

      In accordance with the variation in blood LDL-cholesterol response, that many studies have
      reported previously following substitution of dietary saturated with unsaturated fats, the
      investigators hypothesise that consuming Diet 1 (a high saturated fat diet) for 4 weeks
      followed by diet 2 (a low saturated fat/high unsaturated fat diet) for a further 4 weeks,
      will: 1) produce a variable distribution of responses in LDL-cholesterol that will enable the
      study of associations between the participants' baseline characteristics as possible
      determinants of the observed variation in blood LDL-cholesterol response, and 2) identify two
      distinct subgroups of individuals who either respond or show little or no response in their
      blood LDL- cholesterol. These distinct groups will be defined by the top and bottom ~10% of
      change in the concentration of blood LDL-cholesterol.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Changes in fasting total cholesterol (consisting of LDL-cholesterol and HDL) concentrations
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Fasting triacylglycerol
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: HDL immune functions
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: HDL anti-inflammatory and anti-oxidant (PON-1) properties
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: HDL capacity to promote cholesterol efflux (ex-vivo)
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Fasting insulin, glucose
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Adhesion molecules, markers of vascular function
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Inflammatory markers & adipokines
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: LDL-R gene expression
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Other relevant genes involved in the absorption and metabolism of dietary fat
time frame: Baseline
description: Polymorphic genes with potential influence on the serum LDL response to dietary saturated fat, e.g.: ATP-binding cassette proteins (cholesterol efflux proteins) ABCG5 (e.g. C1950G) ABCG8 (e.g. D19H, C1895T), functional polymorphisms in the farnesoid X receptor (FXR) and bile acid transporters (e.g. solute carrier organics anion 1B1). Fatty acid desaturases (FADS1 and FADS2). The patatin-like phospholipase domain-containing protein (PNPLA3) (e.g. rs738409 C/G), eNOS. Lipid/cholesterol homeostasis: serum apolipoprotein genes: APOE (ε2,ε3,ε4 e.g. rs429358 and rs7412), APOA-I (e.g. -75G/A), APOA4 (e.g. 360-2), APOA5 (e.g. -113/T&gt:c), APOCIII, APOB (e.g. -516C/T). Lipase genes: (e.g. LPL, HL, MGLL). Lipoprotein receptor genes (e.g. pvu11 in the LDL receptor), lipid transfer proteins (e.g. CETP e.g Taq1B, MTP), and other polymorphic genes related to the absorption and metabolism of dietary fat and regulation of lipid/cholesterol homeostasis.
measure: Metabolomic analysis for the determination of the low molecular weight metabolite profiles in the biological fluids
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
description: Analyses conducted by Imperial College London
measure: Changes in faecal bacterial population
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Weight
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
description: BMI will also be calculated (kg/ height in m^2)
measure: Fat mass
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Fat free mass
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Waist circumference
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Hip circumference
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Blood pressure
time frame: Baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
measure: Fasting vascular stiffness
time frame: baseline, 4 weeks (after diet 1), 8 weeks (after diet 2)
description: Measured via pulse wave assessment using the Mobil-O-graph device.
measure: Genotyping for apolipoprotein E to determine the impact of this genotype on changes in the primary and secondary outcome measurements in response to dietary fat intake
time frame: Baseline
arm group label: High SFA diet to low SFA diet
arm group type: Experimental
description: Participants will undergo, sequentially, a high SFA diet (Diet 1) followed by a low SFA diet (Diet 2) for 4 weeks each. Study visits will occur before and after each dietary intervention period. To comply with current UK dietary recommendations, Diets 1 and 2 will both contain ~35% energy from total fat. These diets will be consumed within the homes of free-living participants, by the substitution of ~40g of habitual fat, with either SFA-rich or mono/poly-unsaturated fatty acid-rich (MUFA/PUFA) cooking oils, spreads and snack foods, while maintaining their habitual diet (consistent intake of protein and carbohydrates, including dietary fibre). This will be achieved using a dietary exchange model developed and peer-reviewed for a previous dietary intervention study ('DIVAS') at the University of Reading, U.K.
intervention type: Other
intervention name: High SFA diet (Diet 1)
description: 'Diet 1' will contain ~18% of its total energy as SFA .
arm group label: High SFA diet to low SFA diet
intervention type: Other
intervention name: Low SFA diet (Diet 2)
description: 'Diet 2' will contain ~10% of its total energy as SFA. The SFA-replacement fats will be mixture of PUFA/MUFA.
arm group label: High SFA diet to low SFA diet
criteria: 
gender: Male
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bruce Griffin, PhD
role: Principal Investigator
affiliation: University of Surrey
last name: Julie Lovegrove, PhD
role: Principal Investigator
affiliation: University of Reading
facility: 
facility: 
country: United Kingdom
citation: Vafeiadou K, Weech M, Altowaijri H, Todd S, Yaqoob P, Jackson KG, Lovegrove JA. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. Am J Clin Nutr. 2015 Jul;102(1):40-8. doi: 10.3945/ajcn.114.097089. Epub 2015 May 27.
PMID: 26016869
responsible party type: Principal Investigator
investigator affiliation: University of Surrey
investigator full name: Bruce A. Griffin
investigator title: Professor
sharing ipd: No
provided document: 