<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/NCT04460287</url>
  </required_header>
  <id_info>
    <org_study_id>INA/NM-20010028</org_study_id>
    <nct_id>NCT04460287</nct_id>
  </id_info>
  <brief_title>Bioavailability of Different Formulas Enriched With DHA Using Wet Mixing or Dry Blending Method</brief_title>
  <official_title>Bioavailability of Different Formulas Enriched With DHA Using Wet Mixing or Dry Blending Method</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indonesian Nutrition Association</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indonesian Nutrition Association</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>
      Infants and young children have high nutritional demands in order to support adequate growth&#xD;
      and development, particularly during the transition from complementary feeding at 12 months&#xD;
      of age to a mixed and varied diet at 36 months of age. Omega-3 long chain polyunsaturated&#xD;
      fatty acid (n-3 LC-PUFA) such as docosahexaenoic acid (DHA; 22:6n-3) is the important&#xD;
      constituents of the maturing brain, especially for visual and cognitive development. However&#xD;
      only certain foods, such as fatty fish, contain n-3 LC-PUFA at concentrations sufficient for&#xD;
      their needs. Additionally, these foods that are known to be rich in DHA may not be regularly&#xD;
      provided to infants and toddlers due to concerns about potential food allergies or&#xD;
      methylmercury exposure.&#xD;
&#xD;
      Although the importance of consuming n-3 LC-PUFA and essential fatty acids at the level of&#xD;
      dietary recommendations in late infancy and early childhood (6-24 months) are highlighted,&#xD;
      the current median n-3 LC-PUFA and estimated DHA intakes in toddlers in most countries are&#xD;
      lower than the recommended levels. The European Food Safety Authority (EFSA) recommend that&#xD;
      infants and young children (&lt; 24 months) should consume 100 mg of DHA per day, while for&#xD;
      older children (2-18 years), they recommend a daily intake of 250 mg. In order to bridge the&#xD;
      gap between the current intake and recommended levels of n-3 LC-PUFA, general foods,&#xD;
      especially infant and toddler formulas, should be enriched with n-3 LC-PUFA particularly DHA.&#xD;
      With a growing body of research, the challenge is to find an ideal formula that is&#xD;
      nutritionally balanced and human milk-like, especially with respect to the ratio between&#xD;
      omega-6 and omega-3 fatty acids and DHA level.&#xD;
&#xD;
      In adding DHA into the toddler formula, there are several methods, among others are in the&#xD;
      form of wet mix and dry blending. The aim of this study is to compare the bioavailability of&#xD;
      different methods of adding DHA (dry blend versus wet mix) into formulas in healthy&#xD;
      Indonesian toddlers age 2-3 years old for a period of one month. Furthermore, to evaluate the&#xD;
      stability of milk-based formulas that are supplemented with DHA under same storage&#xD;
      conditions, so as to monitor the stability of infant formula.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will use two phase approaches Phase 1, screening habitual n3 intake. Mothers of&#xD;
      healthy toddlers, non-fish or non-n3 supplement babies (aged 2-3 years old) would be invited&#xD;
      to complete a Food Frequency Questionnaire (FFQ) to determine their habitual dietary intake&#xD;
      of long chain n3 fatty acids. The 120 babies with the lowest long chain n3 intake would be&#xD;
      invited to proceed to phase 2 of the trial.&#xD;
&#xD;
      Phase 2, double blinded, randomized trial. Based on the outcome of the FFQ in phase 1 of the&#xD;
      proposed trial, the 120 babies with the lowest habitual dietary intake will be allocated to&#xD;
      diet in a random order for one month. Blood samples will be collected via dry blood spot kits&#xD;
      at the start, middle and end of the diet along with faecal collection every day.&#xD;
&#xD;
      Groups are Milk drink unfortified (negative control), Milk drink unfortified plus fish oil&#xD;
      (positive control), Milk drink fortified with DHA used wet mixing method and Milk drink&#xD;
      fortified with DHA used dry blending method.&#xD;
&#xD;
      Population and subjects are Indonesian children aged 2-3 years old living in Jakarta will be&#xD;
      selected if they meet the study criteria.&#xD;
&#xD;
      For stage-1: to get 50% of children having habitual low DHA intake, with degree of&#xD;
      significance 5% and degree of reliability 95%, then 385 children will be needed.&#xD;
&#xD;
      For stage-2: This study will include 30 subjects per-study group&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 30, 2020</start_date>
  <completion_date type="Anticipated">January 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2020</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DHA level in RBC lipid and faecal</measure>
    <time_frame>One month</time_frame>
    <description>Blood and faecal specimen</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Healthy Children</condition>
  <arm_group>
    <arm_group_label>Milk Drink Unfortified (Negative Control)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Milk Drink Unfortified Plus Fish Oil (Positive Control)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Milk Drink Fortified with DHA Used Wet Mixing Method</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Milk Drink Fortified with DHA Used Dry Blending Method</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DHA Wet Mixing method</intervention_name>
    <description>Children will drink milk contain 100 mg DHA wet mixing daily for 30 days</description>
    <arm_group_label>Milk Drink Fortified with DHA Used Dry Blending Method</arm_group_label>
    <arm_group_label>Milk Drink Unfortified (Negative Control)</arm_group_label>
    <arm_group_label>Milk Drink Unfortified Plus Fish Oil (Positive Control)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DHA Dry Blending Method</intervention_name>
    <description>Children will drink milk contain 100 mg DHA dry blending daily for 30 days</description>
    <arm_group_label>Milk Drink Fortified with DHA Used Wet Mixing Method</arm_group_label>
    <arm_group_label>Milk Drink Unfortified (Negative Control)</arm_group_label>
    <arm_group_label>Milk Drink Unfortified Plus Fish Oil (Positive Control)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fish Oil</intervention_name>
    <description>Children will have this intervention every day for 30 days</description>
    <arm_group_label>Milk Drink Fortified with DHA Used Dry Blending Method</arm_group_label>
    <arm_group_label>Milk Drink Fortified with DHA Used Wet Mixing Method</arm_group_label>
    <arm_group_label>Milk Drink Unfortified (Negative Control)</arm_group_label>
    <other_name>Children will have milk drink and Fish Oil contain 100 mg/DHA daily for 30 days</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Boys and girls aged 2-3 years old, apparently healthy, living in the study area for&#xD;
             minimally one month and parents permit them to participate in the study by signing the&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Having milk allergy and/or lactose intolerance, high omega-3 intake habit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>3 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diana Sunardi, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Medicine University of Indonesia Cipto Mangunkusumo Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Diana Sunardi, Doctor</last_name>
    <phone>+62816-1646-427</phone>
    <email>diana_sunardi@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Saptawati Bardosono, Doctor</last_name>
    <phone>+62817-149-629</phone>
    <email>tati.bardo@yahoo.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Keim SA, Branum AM. Dietary intake of polyunsaturated fatty acids and fish among US children 12-60 months of age. Matern Child Nutr. 2015 Oct;11(4):987-98. doi: 10.1111/mcn.12077. Epub 2013 Sep 13.</citation>
    <PMID>24034437</PMID>
  </reference>
  <reference>
    <citation>Osendarp, S.J., The role of omega-3 fatty acids in child development. Oléagineux, Corps gras, Lipides, 2011. 18(6): p. 307-313</citation>
  </reference>
  <reference>
    <citation>EFSA Panel on Dietetic Products, N.a.A. and Allergies, Scientific Opinion on the substantiation of a health claim related to DHA and contribution to normal brain development pursuant to Article 14 of Regulation (EC) No 1924/2006. EFSA Journal, 2014. 12(10): p. 3840</citation>
  </reference>
  <reference>
    <citation>Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids. 2003 Apr;38(4):391-8. doi: 10.1007/s11745-003-1074-0.</citation>
    <PMID>12848284</PMID>
  </reference>
  <reference>
    <citation>Innis SM, Vaghri Z, King DJ. n-6 Docosapentaenoic acid is not a predictor of low docosahexaenoic acid status in Canadian preschool children. Am J Clin Nutr. 2004 Sep;80(3):768-73. doi: 10.1093/ajcn/80.3.768.</citation>
    <PMID>15321820</PMID>
  </reference>
  <reference>
    <citation>Barbarich BN, Willows ND, Wang L, Clandinin MT. Polyunsaturated fatty acids and anthropometric indices of children in rural China. Eur J Clin Nutr. 2006 Sep;60(9):1100-7. doi: 10.1038/sj.ejcn.1602424. Epub 2006 Mar 15.</citation>
    <PMID>16538238</PMID>
  </reference>
  <reference>
    <citation>Kim Y, Kim H, Kwon O. Dietary intake of n-3 and n-6 polyunsaturated fatty acids in Korean toddlers 12-24 months of age with comparison to the dietary recommendations. Nutr Res Pract. 2019 Aug;13(4):344-351. doi: 10.4162/nrp.2019.13.4.344. Epub 2019 Jul 24.</citation>
    <PMID>31388411</PMID>
  </reference>
  <reference>
    <citation>Tsuboyama-Kasaoka N, Takizawa A, Tsubota-Utsugi M, Nakade M, Imai E, Kondo A, Yoshida K, Okuda N, Nishi N, Takimoto H. Dietary intake of nutrients with adequate intake values in the dietary reference intakes for Japanese. J Nutr Sci Vitaminol (Tokyo). 2013;59(6):584-95. doi: 10.3177/jnsv.59.584.</citation>
    <PMID>24477258</PMID>
  </reference>
  <reference>
    <citation>Gibson, S. and A. Sidnell, Nutrient adequacy and imbalance among young children aged 1-3 years in the UK. Nutrition bulletin, 2014. 39(2): p. 172-180</citation>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04460287
org study id: INA/NM-20010028
nct id: NCT04460287
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Infants and young children have high nutritional demands in order to support adequate growth
      and development, particularly during the transition from complementary feeding at 12 months
      of age to a mixed and varied diet at 36 months of age. Omega-3 long chain polyunsaturated
      fatty acid (n-3 LC-PUFA) such as docosahexaenoic acid (DHA; 22:6n-3) is the important
      constituents of the maturing brain, especially for visual and cognitive development. However
      only certain foods, such as fatty fish, contain n-3 LC-PUFA at concentrations sufficient for
      their needs. Additionally, these foods that are known to be rich in DHA may not be regularly
      provided to infants and toddlers due to concerns about potential food allergies or
      methylmercury exposure.

      Although the importance of consuming n-3 LC-PUFA and essential fatty acids at the level of
      dietary recommendations in late infancy and early childhood (6-24 months) are highlighted,
      the current median n-3 LC-PUFA and estimated DHA intakes in toddlers in most countries are
      lower than the recommended levels. The European Food Safety Authority (EFSA) recommend that
      infants and young children (< 24 months) should consume 100 mg of DHA per day, while for
      older children (2-18 years), they recommend a daily intake of 250 mg. In order to bridge the
      gap between the current intake and recommended levels of n-3 LC-PUFA, general foods,
      especially infant and toddler formulas, should be enriched with n-3 LC-PUFA particularly DHA.
      With a growing body of research, the challenge is to find an ideal formula that is
      nutritionally balanced and human milk-like, especially with respect to the ratio between
      omega-6 and omega-3 fatty acids and DHA level.

      In adding DHA into the toddler formula, there are several methods, among others are in the
      form of wet mix and dry blending. The aim of this study is to compare the bioavailability of
      different methods of adding DHA (dry blend versus wet mix) into formulas in healthy
      Indonesian toddlers age 2-3 years old for a period of one month. Furthermore, to evaluate the
      stability of milk-based formulas that are supplemented with DHA under same storage
      conditions, so as to monitor the stability of infant formula.
This study will use two phase approaches Phase 1, screening habitual n3 intake. Mothers of
      healthy toddlers, non-fish or non-n3 supplement babies (aged 2-3 years old) would be invited
      to complete a Food Frequency Questionnaire (FFQ) to determine their habitual dietary intake
      of long chain n3 fatty acids. The 120 babies with the lowest long chain n3 intake would be
      invited to proceed to phase 2 of the trial.

      Phase 2, double blinded, randomized trial. Based on the outcome of the FFQ in phase 1 of the
      proposed trial, the 120 babies with the lowest habitual dietary intake will be allocated to
      diet in a random order for one month. Blood samples will be collected via dry blood spot kits
      at the start, middle and end of the diet along with faecal collection every day.

      Groups are Milk drink unfortified (negative control), Milk drink unfortified plus fish oil
      (positive control), Milk drink fortified with DHA used wet mixing method and Milk drink
      fortified with DHA used dry blending method.

      Population and subjects are Indonesian children aged 2-3 years old living in Jakarta will be
      selected if they meet the study criteria.

      For stage-1: to get 50% of children having habitual low DHA intake, with degree of
      significance 5% and degree of reliability 95%, then 385 children will be needed.

      For stage-2: This study will include 30 subjects per-study group
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: DHA level in RBC lipid and faecal
time frame: One month
description: Blood and faecal specimen
arm group label: Milk Drink Unfortified (Negative Control)
arm group type: Placebo Comparator
description: Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days.
arm group label: Milk Drink Unfortified Plus Fish Oil (Positive Control)
arm group type: Active Comparator
description: Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days
arm group label: Milk Drink Fortified with DHA Used Wet Mixing Method
arm group type: Experimental
description: Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days
arm group label: Milk Drink Fortified with DHA Used Dry Blending Method
arm group type: Experimental
description: Children will get the product (packed for its individual portion) that must be consumed once a day for 30 days
intervention type: Dietary Supplement
intervention name: DHA Wet Mixing method
description: Children will drink milk contain 100 mg DHA wet mixing daily for 30 days
arm group label: Milk Drink Fortified with DHA Used Dry Blending Method
arm group label: Milk Drink Unfortified (Negative Control)
arm group label: Milk Drink Unfortified Plus Fish Oil (Positive Control)
intervention type: Dietary Supplement
intervention name: DHA Dry Blending Method
description: Children will drink milk contain 100 mg DHA dry blending daily for 30 days
arm group label: Milk Drink Fortified with DHA Used Wet Mixing Method
arm group label: Milk Drink Unfortified (Negative Control)
arm group label: Milk Drink Unfortified Plus Fish Oil (Positive Control)
intervention type: Dietary Supplement
intervention name: Fish Oil
description: Children will have this intervention every day for 30 days
arm group label: Milk Drink Fortified with DHA Used Dry Blending Method
arm group label: Milk Drink Fortified with DHA Used Wet Mixing Method
arm group label: Milk Drink Unfortified (Negative Control)
other name: Children will have milk drink and Fish Oil contain 100 mg/DHA daily for 30 days
criteria: 
gender: All
minimum age: 2 Years
maximum age: 3 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Diana Sunardi, Doctor
role: Principal Investigator
affiliation: Faculty of Medicine University of Indonesia Cipto Mangunkusumo Hospital
last name: Diana Sunardi, Doctor
phone: +62816-1646-427
email: diana_sunardi@yahoo.com
last name: Saptawati Bardosono, Doctor
phone: +62817-149-629
email: tati.bardo@yahoo.com
citation: Keim SA, Branum AM. Dietary intake of polyunsaturated fatty acids and fish among US children 12-60 months of age. Matern Child Nutr. 2015 Oct;11(4):987-98. doi: 10.1111/mcn.12077. Epub 2013 Sep 13.
PMID: 24034437
citation: Osendarp, S.J., The role of omega-3 fatty acids in child development. Oléagineux, Corps gras, Lipides, 2011. 18(6): p. 307-313
citation: EFSA Panel on Dietetic Products, N.a.A. and Allergies, Scientific Opinion on the substantiation of a health claim related to DHA and contribution to normal brain development pursuant to Article 14 of Regulation (EC) No 1924/2006. EFSA Journal, 2014. 12(10): p. 3840
citation: Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids. 2003 Apr;38(4):391-8. doi: 10.1007/s11745-003-1074-0.
PMID: 12848284
citation: Innis SM, Vaghri Z, King DJ. n-6 Docosapentaenoic acid is not a predictor of low docosahexaenoic acid status in Canadian preschool children. Am J Clin Nutr. 2004 Sep;80(3):768-73. doi: 10.1093/ajcn/80.3.768.
PMID: 15321820
citation: Barbarich BN, Willows ND, Wang L, Clandinin MT. Polyunsaturated fatty acids and anthropometric indices of children in rural China. Eur J Clin Nutr. 2006 Sep;60(9):1100-7. doi: 10.1038/sj.ejcn.1602424. Epub 2006 Mar 15.
PMID: 16538238
citation: Kim Y, Kim H, Kwon O. Dietary intake of n-3 and n-6 polyunsaturated fatty acids in Korean toddlers 12-24 months of age with comparison to the dietary recommendations. Nutr Res Pract. 2019 Aug;13(4):344-351. doi: 10.4162/nrp.2019.13.4.344. Epub 2019 Jul 24.
PMID: 31388411
citation: Tsuboyama-Kasaoka N, Takizawa A, Tsubota-Utsugi M, Nakade M, Imai E, Kondo A, Yoshida K, Okuda N, Nishi N, Takimoto H. Dietary intake of nutrients with adequate intake values in the dietary reference intakes for Japanese. J Nutr Sci Vitaminol (Tokyo). 2013;59(6):584-95. doi: 10.3177/jnsv.59.584.
PMID: 24477258
citation: Gibson, S. and A. Sidnell, Nutrient adequacy and imbalance among young children aged 1-3 years in the UK. Nutrition bulletin, 2014. 39(2): p. 172-180
responsible party type: Sponsor
sharing ipd: No