<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/NCT03306862</url>
  </required_header>
  <id_info>
    <org_study_id>RRC/2017/1704</org_study_id>
    <secondary_id>HS21196 (B2017:123)</secondary_id>
    <nct_id>NCT03306862</nct_id>
  </id_info>
  <brief_title>Effect of Peas in Soup on Blood Glucose Control</brief_title>
  <acronym>PEA4</acronym>
  <official_title>A Randomized, Controlled, Cross-over Trial Examining the Effect of Peas in Soup on Post-prandial Glycaemic Response in Healthy Adults.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Boniface Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Agriculture and Agri-Food Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Boniface Hospital</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>
      This study is part of a group of studies whose overall goal is to accurately define the&#xD;
      physiochemical and structural effects of pea varieties and relate these to blood glucose&#xD;
      attenuation in healthy human volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized, controlled, cross-over study designed to examine the post-prandial glycaemic&#xD;
      response to peas in soup will be conducted at the I.H. Asper Clinical Research Institute in&#xD;
      Winnipeg, Manitoba. Eligible participants who have provided consent will be asked to attend 3&#xD;
      clinic visits in a fasted state. Participants will be given soup containing peas at 2 visits&#xD;
      and soup without peas at 1 visit. At each visit participants will provide 7 capillary blood&#xD;
      samples via finger poke, 5 questionnaires about their appetite and a questionnaire about the&#xD;
      acceptability of the products. Each visit will last approximately 2.5h and be separated by&#xD;
      3-14 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 8, 2017</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Actual">December 21, 2018</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Randomized, controlled, cross-over study</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-prandial glucose</measure>
    <time_frame>120 min</time_frame>
    <description>iAUC for glucose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-prandial insulin</measure>
    <time_frame>120 min</time_frame>
    <description>iAUC for insulin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hunger</measure>
    <time_frame>120 min</time_frame>
    <description>AUC using visual analog scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fullness</measure>
    <time_frame>120 min</time_frame>
    <description>AUC using visual analog scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Desire to eat</measure>
    <time_frame>120 min</time_frame>
    <description>AUC using visual analog scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prospective consumption</measure>
    <time_frame>120 min</time_frame>
    <description>AUC using visual analog scales</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Acceptability of soup color</measure>
    <time_frame>15 min</time_frame>
    <description>Ratings on a scale of 1-9</description>
  </other_outcome>
  <other_outcome>
    <measure>Acceptability of soup aroma</measure>
    <time_frame>15 min</time_frame>
    <description>Ratings on a scale of 1-9</description>
  </other_outcome>
  <other_outcome>
    <measure>Acceptability of soup flavor</measure>
    <time_frame>15 min</time_frame>
    <description>Ratings on a scale of 1-9</description>
  </other_outcome>
  <other_outcome>
    <measure>Acceptability of soup texture</measure>
    <time_frame>15 min</time_frame>
    <description>Ratings on a scale of 1-9</description>
  </other_outcome>
  <other_outcome>
    <measure>Frequency of eating soup</measure>
    <time_frame>15 min</time_frame>
    <description>Ratings on a scale of 1-9</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal side effects</measure>
    <time_frame>24 h</time_frame>
    <description>Incidence of gastrointestinal effects</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Post-prandial Glycaemia</condition>
  <arm_group>
    <arm_group_label>Whole yellow pea</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Soup containing 25g available carbohydrates from whole yellow peas. Intervention: Whole yellow pea soup</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Split yellow pea</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Soup containing 25g available carbohydrates from split yellow peas. Intervention: Split yellow pea soup</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Potato</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Soup containing 25g available carbohydrates from potatoes. Intervention: Potato soup</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Whole yellow pea soup</intervention_name>
    <description>Soup containing whole yellow peas</description>
    <arm_group_label>Whole yellow pea</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Split yellow pea soup</intervention_name>
    <description>Soup containing split yellow peas</description>
    <arm_group_label>Split yellow pea</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Potato soup</intervention_name>
    <description>Soup containing potatoes</description>
    <arm_group_label>Potato</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Generally healthy male or female, between the age of 18-40 years;&#xD;
&#xD;
          2. Body mass index (BMI) 18.5-30.0 kg/m2;&#xD;
&#xD;
          3. Habitually consume breakfast, lunch and dinner in the morning, mid-day and evening,&#xD;
             respectively.&#xD;
&#xD;
          4. Willing to provide informed consent;&#xD;
&#xD;
          5. Willing/able to comply with the requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating;&#xD;
&#xD;
          2. Medical history of diabetes mellitus, fasting blood glucose ≥6.1 mmol/L, HbA1c ≥6.0%,&#xD;
             or use of insulin or oral medication to control blood sugar;&#xD;
&#xD;
          3. Medical history of cardiovascular disease;&#xD;
&#xD;
          4. Systolic blood pressure &gt;140 mmHg or diastolic blood pressure &gt;90 mmHg;&#xD;
&#xD;
          5. Fasting plasma total cholesterol &gt;7.8 mmol/L;&#xD;
&#xD;
          6. Fasting plasma HDL &lt;0.9 mmol/L;&#xD;
&#xD;
          7. Fasting plasma LDL &gt;5.0 mmol/L;&#xD;
&#xD;
          8. Fasting plasma triglycerides &gt;2.3 mmol/L;&#xD;
&#xD;
          9. Major surgery within the last 3 months;&#xD;
&#xD;
         10. Medical history of inflammatory disease (ie. Systemic lupus erythematosis, rheumatoid&#xD;
             arthritis, psoriasis) or use of any corticosteroid medications within 3 months;&#xD;
&#xD;
         11. Medical history of liver disease or liver dysfunction (defined as plasma AST or ALT&#xD;
             ≥1.5 times the upper limit of normal (ULN));&#xD;
&#xD;
         12. Medical history of kidney disease or kidney dysfunction (defined as blood urea&#xD;
             nitrogen and creatinine ≥ 1.8 times the ULN));&#xD;
&#xD;
         13. Presence of a gastrointestinal disorder, daily use of any stomach acid-lowering&#xD;
             medications or laxatives (including fibre supplements) within the past month or&#xD;
             antibiotic use within the past 6 weeks;&#xD;
&#xD;
         14. Active treatment for any type of cancer within 1 year prior to study start;&#xD;
&#xD;
         15. Shift worker (a system of employment where an individual's normal hours of work are in&#xD;
             part, outside the period of normal working day; 6am and 8pm);&#xD;
&#xD;
         16. Smoking, use of tobacco or a nicotine replacement product (within the last 3 months);&#xD;
&#xD;
         17. Allergies to peas;&#xD;
&#xD;
         18. Aversion or unwillingness to eat study foods;&#xD;
&#xD;
         19. Consuming &gt;4 servings of pulses per week;&#xD;
&#xD;
         20. Use of any prescription or non-prescription drug, herbal or nutritional supplement&#xD;
             known to affect glycaemia or appetite;&#xD;
&#xD;
         21. Participation in another clinical trial, current or in the past 4 weeks;&#xD;
&#xD;
         22. Unstable body weight (defined as &gt;5% change in 3 months) or actively participating in&#xD;
             a weight loss program.&#xD;
&#xD;
         23. Other medical, psychiatric, or behavioral factors that in the judgment of the&#xD;
             principal Investigator may interfere with study participation or the ability to follow&#xD;
             the intervention protocol;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heather Blewett, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Agriculture and Agri-Food Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>I.H. Asper Clinical Research Institute</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R2H2A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Public Health Agency of Canada and the Canadian Institute for Health Information. Obesity in Canada: A joint report from the Public Health Agency of Canada and the Canadian institute for health information. Government of Canada; 2011.</citation>
  </reference>
  <reference>
    <citation>Public Health Authority of Canada. Diabetes in Canada: Facts and figures from a public health perspective. 2011.</citation>
  </reference>
  <reference>
    <citation>Sievenpiper JL, Kendall CW, Esfahani A, Wong JM, Carleton AJ, Jiang HY, Bazinet RP, Vidgen E, Jenkins DJ. Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people with and without diabetes. Diabetologia. 2009 Aug;52(8):1479-95. doi: 10.1007/s00125-009-1395-7. Epub 2009 Jun 13.</citation>
    <PMID>19526214</PMID>
  </reference>
  <reference>
    <citation>Hamberg O, Rumessen JJ, Gudmand-Hoyer E. Blood glucose response to pea fiber: comparisons with sugar beet fiber and wheat bran. Am J Clin Nutr. 1989 Aug;50(2):324-8. doi: 10.1093/ajcn/50.2.324.</citation>
    <PMID>2547300</PMID>
  </reference>
  <reference>
    <citation>Marinangeli CP, Jones PJ. Chronic intake of fractionated yellow pea flour reduces postprandial energy expenditure and carbohydrate oxidation. J Med Food. 2011 Dec;14(12):1654-62. doi: 10.1089/jmf.2010.0255.</citation>
    <PMID>22145774</PMID>
  </reference>
  <reference>
    <citation>Smith CE, Mollard RC, Luhovyy BL, Anderson GH. The effect of yellow pea protein and fibre on short-term food intake, subjective appetite and glycaemic response in healthy young men. Br J Nutr. 2012 Aug;108 Suppl 1:S74-80. doi: 10.1017/S0007114512000700.</citation>
    <PMID>22916818</PMID>
  </reference>
  <reference>
    <citation>Jenkins DJ, Thorne MJ, Camelon K, Jenkins A, Rao AV, Taylor RH, Thompson LU, Kalmusky J, Reichert R, Francis T. Effect of processing on digestibility and the blood glucose response: a study of lentils. Am J Clin Nutr. 1982 Dec;36(6):1093-101. doi: 10.1093/ajcn/36.6.1093.</citation>
    <PMID>6293296</PMID>
  </reference>
  <reference>
    <citation>Li H, Song F, Xing J, Tsao R, Liu Z, Liu S. Screening and structural characterization of alpha-glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MS(n) and SORI-CID FTICR MS. J Am Soc Mass Spectrom. 2009 Aug;20(8):1496-503. doi: 10.1016/j.jasms.2009.04.003. Epub 2009 Apr 14.</citation>
    <PMID>19443236</PMID>
  </reference>
  <reference>
    <citation>Habtemariam S. A-glucosidase inhibitory activity of kaempferol-3-O-rutinoside. Nat Prod Commun. 2011 Feb;6(2):201-3.</citation>
    <PMID>21425674</PMID>
  </reference>
  <reference>
    <citation>Ames N, Blewett H, Storsley J, Thandapilly SJ, Zahradka P, Taylor C. A double-blind randomised controlled trial testing the effect of a barley product containing varying amounts and types of fibre on the postprandial glucose response of healthy volunteers. Br J Nutr. 2015 May 14;113(9):1373-83. doi: 10.1017/S0007114515000367. Epub 2015 Apr 8.</citation>
    <PMID>25850814</PMID>
  </reference>
  <reference>
    <citation>Rabiee A, Magruder JT, Grant C, Salas-Carrillo R, Gillette A, DuBois J, Shannon RP, Andersen DK, Elahi D. Accuracy and reliability of the Nova StatStrip(R) glucose meter for real-time blood glucose determinations during glucose clamp studies. J Diabetes Sci Technol. 2010 Sep 1;4(5):1195-201. doi: 10.1177/193229681000400519.</citation>
    <PMID>20920440</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Boniface Hospital</investigator_affiliation>
    <investigator_full_name>Dr. Heather Blewett</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>blood sugar</keyword>
  <keyword>insulin</keyword>
  <keyword>peas</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results in a publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>From the time the data is collected until the manuscript is accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Dan Ramdath, Sora Ludwig and Michel Aliani will have access to data necessary for manuscript preparation.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03306862
org study id: RRC/2017/1704
secondary id: HS21196 (B2017:123)
nct id: NCT03306862
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is part of a group of studies whose overall goal is to accurately define the
      physiochemical and structural effects of pea varieties and relate these to blood glucose
      attenuation in healthy human volunteers.
A randomized, controlled, cross-over study designed to examine the post-prandial glycaemic
      response to peas in soup will be conducted at the I.H. Asper Clinical Research Institute in
      Winnipeg, Manitoba. Eligible participants who have provided consent will be asked to attend 3
      clinic visits in a fasted state. Participants will be given soup containing peas at 2 visits
      and soup without peas at 1 visit. At each visit participants will provide 7 capillary blood
      samples via finger poke, 5 questionnaires about their appetite and a questionnaire about the
      acceptability of the products. Each visit will last approximately 2.5h and be separated by
      3-14 days.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, controlled, cross-over study
primary purpose: Prevention
masking: None (Open Label)
measure: Post-prandial glucose
time frame: 120 min
description: iAUC for glucose
measure: Post-prandial insulin
time frame: 120 min
description: iAUC for insulin
measure: Hunger
time frame: 120 min
description: AUC using visual analog scales
measure: Fullness
time frame: 120 min
description: AUC using visual analog scales
measure: Desire to eat
time frame: 120 min
description: AUC using visual analog scales
measure: Prospective consumption
time frame: 120 min
description: AUC using visual analog scales
measure: Acceptability of soup color
time frame: 15 min
description: Ratings on a scale of 1-9
measure: Acceptability of soup aroma
time frame: 15 min
description: Ratings on a scale of 1-9
measure: Acceptability of soup flavor
time frame: 15 min
description: Ratings on a scale of 1-9
measure: Acceptability of soup texture
time frame: 15 min
description: Ratings on a scale of 1-9
measure: Frequency of eating soup
time frame: 15 min
description: Ratings on a scale of 1-9
measure: Gastrointestinal side effects
time frame: 24 h
description: Incidence of gastrointestinal effects
arm group label: Whole yellow pea
arm group type: Experimental
description: Soup containing 25g available carbohydrates from whole yellow peas. Intervention: Whole yellow pea soup
arm group label: Split yellow pea
arm group type: Experimental
description: Soup containing 25g available carbohydrates from split yellow peas. Intervention: Split yellow pea soup
arm group label: Potato
arm group type: Placebo Comparator
description: Soup containing 25g available carbohydrates from potatoes. Intervention: Potato soup
intervention type: Dietary Supplement
intervention name: Whole yellow pea soup
description: Soup containing whole yellow peas
arm group label: Whole yellow pea
intervention type: Dietary Supplement
intervention name: Split yellow pea soup
description: Soup containing split yellow peas
arm group label: Split yellow pea
intervention type: Dietary Supplement
intervention name: Potato soup
description: Soup containing potatoes
arm group label: Potato
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Heather Blewett, PhD
role: Principal Investigator
affiliation: Agriculture and Agri-Food Canada
facility: 
country: Canada
citation: Public Health Agency of Canada and the Canadian Institute for Health Information. Obesity in Canada: A joint report from the Public Health Agency of Canada and the Canadian institute for health information. Government of Canada; 2011.
citation: Public Health Authority of Canada. Diabetes in Canada: Facts and figures from a public health perspective. 2011.
citation: Sievenpiper JL, Kendall CW, Esfahani A, Wong JM, Carleton AJ, Jiang HY, Bazinet RP, Vidgen E, Jenkins DJ. Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people with and without diabetes. Diabetologia. 2009 Aug;52(8):1479-95. doi: 10.1007/s00125-009-1395-7. Epub 2009 Jun 13.
PMID: 19526214
citation: Hamberg O, Rumessen JJ, Gudmand-Hoyer E. Blood glucose response to pea fiber: comparisons with sugar beet fiber and wheat bran. Am J Clin Nutr. 1989 Aug;50(2):324-8. doi: 10.1093/ajcn/50.2.324.
PMID: 2547300
citation: Marinangeli CP, Jones PJ. Chronic intake of fractionated yellow pea flour reduces postprandial energy expenditure and carbohydrate oxidation. J Med Food. 2011 Dec;14(12):1654-62. doi: 10.1089/jmf.2010.0255.
PMID: 22145774
citation: Smith CE, Mollard RC, Luhovyy BL, Anderson GH. The effect of yellow pea protein and fibre on short-term food intake, subjective appetite and glycaemic response in healthy young men. Br J Nutr. 2012 Aug;108 Suppl 1:S74-80. doi: 10.1017/S0007114512000700.
PMID: 22916818
citation: Jenkins DJ, Thorne MJ, Camelon K, Jenkins A, Rao AV, Taylor RH, Thompson LU, Kalmusky J, Reichert R, Francis T. Effect of processing on digestibility and the blood glucose response: a study of lentils. Am J Clin Nutr. 1982 Dec;36(6):1093-101. doi: 10.1093/ajcn/36.6.1093.
PMID: 6293296
citation: Li H, Song F, Xing J, Tsao R, Liu Z, Liu S. Screening and structural characterization of alpha-glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MS(n) and SORI-CID FTICR MS. J Am Soc Mass Spectrom. 2009 Aug;20(8):1496-503. doi: 10.1016/j.jasms.2009.04.003. Epub 2009 Apr 14.
PMID: 19443236
citation: Habtemariam S. A-glucosidase inhibitory activity of kaempferol-3-O-rutinoside. Nat Prod Commun. 2011 Feb;6(2):201-3.
PMID: 21425674
citation: Ames N, Blewett H, Storsley J, Thandapilly SJ, Zahradka P, Taylor C. A double-blind randomised controlled trial testing the effect of a barley product containing varying amounts and types of fibre on the postprandial glucose response of healthy volunteers. Br J Nutr. 2015 May 14;113(9):1373-83. doi: 10.1017/S0007114515000367. Epub 2015 Apr 8.
PMID: 25850814
citation: Rabiee A, Magruder JT, Grant C, Salas-Carrillo R, Gillette A, DuBois J, Shannon RP, Andersen DK, Elahi D. Accuracy and reliability of the Nova StatStrip(R) glucose meter for real-time blood glucose determinations during glucose clamp studies. J Diabetes Sci Technol. 2010 Sep 1;4(5):1195-201. doi: 10.1177/193229681000400519.
PMID: 20920440
responsible party type: Principal Investigator
investigator affiliation: St. Boniface Hospital
investigator full name: Dr. Heather Blewett
investigator title: Principal Investigator
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: From the time the data is collected until the manuscript is accepted for publication.
ipd access criteria: Dan Ramdath, Sora Ludwig and Michel Aliani will have access to data necessary for manuscript preparation.