<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/NCT02243969</url>
  </required_header>
  <id_info>
    <org_study_id>MEC 13-3-064</org_study_id>
    <nct_id>NCT02243969</nct_id>
  </id_info>
  <brief_title>Alpha-linolenic Acid and Blood Pressure</brief_title>
  <acronym>VASALA</acronym>
  <official_title>Effects of Alpha-linolenic Acid on 24h-ambulatory Mean Arterial Pressure in Untreated High-normal and Stage I Hypertensive Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Unilever R&amp;D</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Increased intakes of n-3 long chain polyunsaturated fatty acids eicosapentanoic&#xD;
      acid (EPA) and docosahexaenoic acid (DHA), mainly found in fatty fish, are recommended for&#xD;
      the prevention of coronary heart disease. Alpha-linolenic acid (ALA, C18:3n-3) is the most&#xD;
      common vegetable-oil based n-3 fatty acid. Evidence exists that ALA supplementation can also&#xD;
      have a protective effect on the development on cardiovascular disease, but may exert its&#xD;
      cardio protective effects through different routes. The benefit may (partly) be due to blood&#xD;
      pressure lowering. However, evidence for beneficial effects of ALA on blood pressure is&#xD;
      conflicting. Therefore, we propose to investigate the effect of flaxseed oil, high in ALA,&#xD;
      using a study powered on 24-hour blood pressure, in a population with high normal blood&#xD;
      pressure and mild hypertension.&#xD;
&#xD;
      Objective: To study the effects of flaxseed oil, rich in ALA on 24h-ambulatory mean arterial&#xD;
      pressure (MAP) in men and women with high-normal blood pressure and mild hypertension&#xD;
      compared to high oleic sunflower oil, poor in ALA.&#xD;
&#xD;
      Study design: Using a double blind randomized, placebo-controlled parallel design, subjects&#xD;
      will receive at random daily 10 g of flaxseed oil or a high-oleic acid sunflower oil (HOSF)&#xD;
      as control for twelve weeks, with a run-in period of 14 days in advance.&#xD;
&#xD;
      Study population: 72 men and women, aged 40-70 years, with untreated high-normal blood&#xD;
      pressure and stage I hypertension and a body mass index between 25 and 35 kg/m2 will&#xD;
      participate in the run-in and intervention period. It is estimated that 144 subject have to&#xD;
      be screened to find 72 subjects that will enter the run-in period.&#xD;
&#xD;
      Intervention: During the run-in period, subjects will receive daily 10 g of palm super olein&#xD;
      oil. During the intervention period subjects receive either 10 g of HOSF or flaxseed oil. All&#xD;
      oils are provided in bottles of 5 g, one will be consumed at breakfast or lunch and one at&#xD;
      dinner.&#xD;
&#xD;
      Main study parameters/endpoints: The main study parameter is the change in 24h-ambulatory&#xD;
      mean arterial pressure (MAP)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>24h-ambulatory mean arterial pressure (MAP)</measure>
    <time_frame>Baseline and end of intervention period (week 2 and 14)</time_frame>
    <description>Ambulatory blood pressure measurements will be performed using an automated blood pressure device with 15-minute intervals during the day and 30-minute intervals during the night.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postprandial flow mediated dilatation (FMD)</measure>
    <time_frame>End of intervention period (week 14)</time_frame>
    <description>The brachial artery FMD will be measured in a subset (n=20 per group) of the study population. FMD will be measured before and 2 hours after a fat load.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Night, day and early morning 24h-ambulatory MAP, SBP and DBP</measure>
    <time_frame>Baseline and end of intervention (week 2 and 14)</time_frame>
    <description>Ambulatory blood pressure measurements will be performed using an automated blood pressure device with 15-minute intervals during the day and 30-minute intervals during the night.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systolic, diastolic and MAP office blood pressure</measure>
    <time_frame>Measured every visit (week 1,2,8,14)</time_frame>
    <description>Each visit blood pressure will be measured in four-fold with 1-minute interval (the first measurement will be discarded and the last three measurement will be averaged) using a calibrated device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The fatty-acid profile of plasma phospholipids</measure>
    <time_frame>Baseline and end of intervention period (week 2 and 14)</time_frame>
    <description>measured in fasting plasma samples</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pulse wave velocity (PWV)</measure>
    <time_frame>Baseline and end of intervention period (week 2 and 14)</time_frame>
    <description>PWV will be determined by extending data from standard brachial artery blood pressure measurements</description>
  </other_outcome>
  <other_outcome>
    <measure>Retinal microvasculature</measure>
    <time_frame>Baseline and end of intervention period (week 2 and 14)</time_frame>
    <description>Measured as AV-ratio and vessel diameter from digitized analogue fundus photographs</description>
  </other_outcome>
  <other_outcome>
    <measure>Fasting and postprandial lipid and glucose metabolism</measure>
    <time_frame>Every visit (week 1,2,8,14) Postprandial in subset of n=20 per group</time_frame>
    <description>Postprandial glucose at time point 15,30,45,60,90,120,180,240 minutes Postprandial lipids at time point 60, 120, 180, 240 minutes</description>
  </other_outcome>
  <other_outcome>
    <measure>Fasting and postprandial serum biomarkers for low-grade systemic inflammation (hsCRP, IL-6) and endothelial function (sICAM-1, VCAM-1, MCP-1 and sE-Selectin)</measure>
    <time_frame>Every visit (week 1,2,8,14) Postprandial in subset of n=20 per group at time point 60, 120, 240 minutes</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Hypertension</condition>
  <condition>Lipid Metabolism Disorders</condition>
  <arm_group>
    <arm_group_label>flaxseed oil (rich in α-linolenic acid )</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>high oleic sunflower oil</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Flaxseed oil</intervention_name>
    <description>The flaxseed oil will be provided in vials containing 5 g of oil, and should be taken for twelve weeks during the experimental period twice a day</description>
    <arm_group_label>flaxseed oil (rich in α-linolenic acid )</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>high oleic sunflower oil (HOSF)</intervention_name>
    <description>The HOSF will be provided in vials containing 5 g of oil, and should be taken for twelve weeks during the experimental period twice a day</description>
    <arm_group_label>high oleic sunflower oil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Quetelet-index between 25-35 kg/m2&#xD;
&#xD;
          -  High-normal blood pressure defined as systolic blood pressure between 130-139 mmHg&#xD;
             and/or diastolic blood pressure between 85-89 mmHg. Or stage I hypertension defined as&#xD;
             systolic blood pressure between 140-159 mmHg and/or diastolic blood pressure between&#xD;
             90-99 mmHg.&#xD;
&#xD;
          -  Mean serum total cholesterol/HDL cholesterol ratio &lt; 8&#xD;
&#xD;
          -  Mean serum triacylglycerol &lt; 4.5 mmol/L&#xD;
&#xD;
          -  Mean plasma glucose &lt; 7.0 mmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable body weight (weight gain or loss &gt;2 kg in the past 3 months)&#xD;
&#xD;
          -  Use of antihypertensive or anticoagulant medication&#xD;
&#xD;
          -  Indication for treatment with medication according to the Standard for cardiovascular&#xD;
             risk management of the Dutch general practitioners community (NHG)&#xD;
&#xD;
          -  Usage of non-steroidal anti-inflammatory drugs (such as aspirin, ibuprofen, naproxen)&#xD;
             and not able or willing to stop taking them from at least 4 weeks prior to the study&#xD;
&#xD;
          -  Use of medication or a diet known to affect serum lipid or glucose metabolism&#xD;
&#xD;
          -  Women with expected changes in the use of oral contraceptives or estrogen replacement&#xD;
             therapy during the study period&#xD;
&#xD;
          -  Women lactating, pregnant or intend to become pregnant during study&#xD;
&#xD;
          -  Active cardiovascular disease like congestive heart failure or recent (&lt;6 months)&#xD;
             event (acute myocardial infarction, cerebro vascular accident)&#xD;
&#xD;
          -  Severe medical conditions that might interfere with the study such as diabetes&#xD;
             mellitus, epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel&#xD;
             diseases and rheumatoid arthritis&#xD;
&#xD;
          -  Smoking or recently quit smoking (&lt;1 years)&#xD;
&#xD;
          -  Abuse of drugs&#xD;
&#xD;
          -  More than 21 alcohol consumptions per week for men and 14 consumptions for women&#xD;
&#xD;
          -  Reported intense sporting activities &gt; 10 h/w&#xD;
&#xD;
          -  Not possible or difficult to venipuncture as evidenced during the screening visits&#xD;
&#xD;
          -  Use of an investigational product within the previous 30 days&#xD;
&#xD;
          -  Not willing to stop the consumption of vitamin supplements, fish oil capsules or&#xD;
             products rich in plant stanol or sterol esters 3 weeks before the start of the study&#xD;
&#xD;
          -  Not willing to give up being a blood donor (or having donated blood) from 8 weeks&#xD;
             before the start of the study and during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald P Mensink, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229 ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>May 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>March 21, 2016</last_update_submitted>
  <last_update_submitted_qc>March 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>n-3 polyunsaturated fatty acids</keyword>
  <keyword>Alpha-linolenic acid</keyword>
  <keyword>Blood pressure</keyword>
  <keyword>Vascular function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Lipid Metabolism Disorders</mesh_term>
  </condition_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/NCT02243969
org study id: MEC 13-3-064
nct id: NCT02243969
lead sponsor: 
collaborator: 
has dmc: Yes
Rationale: Increased intakes of n-3 long chain polyunsaturated fatty acids eicosapentanoic
      acid (EPA) and docosahexaenoic acid (DHA), mainly found in fatty fish, are recommended for
      the prevention of coronary heart disease. Alpha-linolenic acid (ALA, C18:3n-3) is the most
      common vegetable-oil based n-3 fatty acid. Evidence exists that ALA supplementation can also
      have a protective effect on the development on cardiovascular disease, but may exert its
      cardio protective effects through different routes. The benefit may (partly) be due to blood
      pressure lowering. However, evidence for beneficial effects of ALA on blood pressure is
      conflicting. Therefore, we propose to investigate the effect of flaxseed oil, high in ALA,
      using a study powered on 24-hour blood pressure, in a population with high normal blood
      pressure and mild hypertension.

      Objective: To study the effects of flaxseed oil, rich in ALA on 24h-ambulatory mean arterial
      pressure (MAP) in men and women with high-normal blood pressure and mild hypertension
      compared to high oleic sunflower oil, poor in ALA.

      Study design: Using a double blind randomized, placebo-controlled parallel design, subjects
      will receive at random daily 10 g of flaxseed oil or a high-oleic acid sunflower oil (HOSF)
      as control for twelve weeks, with a run-in period of 14 days in advance.

      Study population: 72 men and women, aged 40-70 years, with untreated high-normal blood
      pressure and stage I hypertension and a body mass index between 25 and 35 kg/m2 will
      participate in the run-in and intervention period. It is estimated that 144 subject have to
      be screened to find 72 subjects that will enter the run-in period.

      Intervention: During the run-in period, subjects will receive daily 10 g of palm super olein
      oil. During the intervention period subjects receive either 10 g of HOSF or flaxseed oil. All
      oils are provided in bottles of 5 g, one will be consumed at breakfast or lunch and one at
      dinner.

      Main study parameters/endpoints: The main study parameter is the change in 24h-ambulatory
      mean arterial pressure (MAP)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 24h-ambulatory mean arterial pressure (MAP)
time frame: Baseline and end of intervention period (week 2 and 14)
description: Ambulatory blood pressure measurements will be performed using an automated blood pressure device with 15-minute intervals during the day and 30-minute intervals during the night.
measure: Postprandial flow mediated dilatation (FMD)
time frame: End of intervention period (week 14)
description: The brachial artery FMD will be measured in a subset (n=20 per group) of the study population. FMD will be measured before and 2 hours after a fat load.
measure: Night, day and early morning 24h-ambulatory MAP, SBP and DBP
time frame: Baseline and end of intervention (week 2 and 14)
description: Ambulatory blood pressure measurements will be performed using an automated blood pressure device with 15-minute intervals during the day and 30-minute intervals during the night.
measure: Systolic, diastolic and MAP office blood pressure
time frame: Measured every visit (week 1,2,8,14)
description: Each visit blood pressure will be measured in four-fold with 1-minute interval (the first measurement will be discarded and the last three measurement will be averaged) using a calibrated device.
measure: The fatty-acid profile of plasma phospholipids
time frame: Baseline and end of intervention period (week 2 and 14)
description: measured in fasting plasma samples
measure: Pulse wave velocity (PWV)
time frame: Baseline and end of intervention period (week 2 and 14)
description: PWV will be determined by extending data from standard brachial artery blood pressure measurements
measure: Retinal microvasculature
time frame: Baseline and end of intervention period (week 2 and 14)
description: Measured as AV-ratio and vessel diameter from digitized analogue fundus photographs
measure: Fasting and postprandial lipid and glucose metabolism
time frame: Every visit (week 1,2,8,14) Postprandial in subset of n=20 per group
description: Postprandial glucose at time point 15,30,45,60,90,120,180,240 minutes Postprandial lipids at time point 60, 120, 180, 240 minutes
measure: Fasting and postprandial serum biomarkers for low-grade systemic inflammation (hsCRP, IL-6) and endothelial function (sICAM-1, VCAM-1, MCP-1 and sE-Selectin)
time frame: Every visit (week 1,2,8,14) Postprandial in subset of n=20 per group at time point 60, 120, 240 minutes
arm group label: flaxseed oil (rich in α-linolenic acid )
arm group type: Experimental
arm group label: high oleic sunflower oil
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Flaxseed oil
description: The flaxseed oil will be provided in vials containing 5 g of oil, and should be taken for twelve weeks during the experimental period twice a day
arm group label: flaxseed oil (rich in α-linolenic acid )
intervention type: Dietary Supplement
intervention name: high oleic sunflower oil (HOSF)
description: The HOSF will be provided in vials containing 5 g of oil, and should be taken for twelve weeks during the experimental period twice a day
arm group label: high oleic sunflower oil
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ronald P Mensink, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Metabolic Diseases
mesh term: Lipid Metabolism Disorders