<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/NCT03787394</url>
  </required_header>
  <id_info>
    <org_study_id>NL67908.081.18</org_study_id>
    <nct_id>NCT03787394</nct_id>
  </id_info>
  <brief_title>Sensory and Hedonic Effects of FAAA-conjugates Added to Food Products</brief_title>
  <official_title>Sensory and Hedonic Effects of FAAA-conjugates Added to Food Products</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wageningen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wageningen University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: According to preliminary observations provided by the research and development&#xD;
      department (R&amp;D) of Givaudan, addition of specific fatty acid-amino acid (FAAA)-conjugates to&#xD;
      a wide range of food products resulted in an enhancement of several sensory and hedonic&#xD;
      effects. Such effects could be attributed to the so-called kokumi sensation, a taste concept&#xD;
      that has been described as a &quot;taste enhancer&quot; that magnifies and lengthens all the other five&#xD;
      basic tastes. The exact mechanisms of the kokumi sensation are as of yet unclear. Perception&#xD;
      of the kokumi sensation depends on the context of other taste compounds and integration into&#xD;
      food matrices. A systematic investigation is necessary to objectively evaluate whether the&#xD;
      addition of specific FAAA-conjugates results in the enhancement of sensory and hedonic&#xD;
      effects. Furthermore, we want to assess the dependency of these effects on the food matrix.&#xD;
      To do so, a combination of discrimination, descriptive and hedonic testing will be carried&#xD;
      out.&#xD;
&#xD;
      Objectives: The primary objectives are: to determine if there is a perceivable difference&#xD;
      between plain and FAAA-enriched versions of selected food products and describe sensory&#xD;
      and/or hedonic differences between them; to assess the dependency of FAAA-conjugates on the&#xD;
      food matrix.&#xD;
&#xD;
      Study design: A two-step, randomised controlled intervention study will be carried out. Study&#xD;
      population: 40 healthy, adult (18-55 years) males and females (BMI 18 - 27 kg/m2) from&#xD;
      Wageningen and surroundings will be included.&#xD;
&#xD;
      Intervention (if applicable): FAAA-conjugates: in step one, FAAA-conjugates will be&#xD;
      integrated into food products; in step two, FAAA-conjugates will both be administered&#xD;
      separately (using a tasteless mouthwash) and integrated into food products.&#xD;
&#xD;
      Main study parameters/endpoints: The primary outcome parameters are: proportion of correct&#xD;
      answers (discrimination testing); sensory evaluation score means (descriptive testing); and&#xD;
      hedonic evaluation score means (hedonic testing).&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: The current study is non-therapeutic to subjects. Risks associated with&#xD;
      participation are negligible and compared to other studies, the burden can be considered low.&#xD;
      The FAAA-conjugates used in the intervention are declared &quot;generally recognised as safe&quot;&#xD;
      (GRAS) by the Flavour Extract Manufacturers Association (FEMA) and pose no known adverse&#xD;
      health effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      FAAA conjugates are compounds containing different long-chain fatty acids and simple amino&#xD;
      acids. They are involved in multiple signalling pathways playing a role in the regulation of&#xD;
      homeostatic and non-homeostatic eating behaviour (Jager &amp; Witkamp, 2014). FAAA-conjugates are&#xD;
      naturally occurring in various animal and plant food sources, yet their dietary relevance and&#xD;
      exact mechanism of action remains unclear. Notwithstanding, they have been related to&#xD;
      improved food sensations and hedonic effects (Jager &amp; Witkamp, 2014; Witkamp, 2018; Yoshida&#xD;
      et al., 2013). FAAA compounds have been declared GRAS by FEMA, which guarantees their safe&#xD;
      use in commercially available food products (Flavour Extract Manufacturers Association,&#xD;
      2018).&#xD;
&#xD;
      According to preliminary observations provided by the research and development department&#xD;
      (R&amp;D) of Givaudan, the addition of specific FAAA-conjugates to a range of food products&#xD;
      resulted in an enhancement of several sensory- and hedonic effects in product evaluation.&#xD;
      Panellists reported accentuated palatability; aftertaste masking; enhanced fat, sweet, salt&#xD;
      and umami perception; and mouthfeel improvement. However, the reproducibility of these&#xD;
      results is questionable, as substantial variation in the effects arose both within and&#xD;
      between a small sample of volunteers. It is unclear whether these effects are specific for&#xD;
      and dependent on integration of these conjugates in a certain food matrix, or if they have a&#xD;
      more general boosting effect, relevant for taste or flavour. Perhaps the boosting effect also&#xD;
      affects other sensory domains (e.g. vision).&#xD;
&#xD;
      The aforementioned reported sensory/hedonic effects could be attributed to what has been&#xD;
      described in literature as the kokumi sensation, which is related to activation of&#xD;
      calcium-sensing receptors on the human tongue, albeit the exact mechanism remains to be&#xD;
      elucidated (Feng, Zhang, Zhuang, Zhou, &amp; Xu, 2016; Kuroda &amp; Miyamura, 2015; Ohsu et al.,&#xD;
      2010). Although Kokumi is associated with taste perception, it is most likely not a primary&#xD;
      taste, since its effects exist in the context of other taste compounds. On their own, kokumi&#xD;
      compounds elicit only very slight or no taste sensations but incorporated in a food matrix&#xD;
      they can enhance other taste sensations. The threshold concentration of kokumi compounds in a&#xD;
      plain water solution to induce a taste sensation is usually very high, while the threshold&#xD;
      concentration in food to enhance other taste sensations can be very low. (Dunkel, Koster, &amp;&#xD;
      Hofmann, 2007; Feng et al., 2016; Kuroda &amp; Miyamura, 2015).&#xD;
&#xD;
      On the basis of preliminary testing done by R&amp;D Givaudan, the study described in the current&#xD;
      protocol aims to systematically investigate the sensory and hedonic effects of&#xD;
      FAAA-conjugates. To do so, specific FAAA-conjugates will be integrated into two food products&#xD;
      (one sweet (chocolate milk) and one savoury (salad dressing), which will be sensorially and&#xD;
      hedonically evaluated. Furthermore, the dependency of FAAA-conjugates on the food matrix will&#xD;
      be studied by administering them separately from food products. An untrained panel will be&#xD;
      used, since consumers are not only capable of providing accurate and reliable information&#xD;
      about product sensory characteristics, but can also serve as a measure of potential&#xD;
      performance of the product in the marketplace (Ares &amp; Varela, 2017; Lawless &amp; Heymann, 2010).&#xD;
&#xD;
      If results are in line with the aforementioned preliminary observations, they can add to the&#xD;
      body of knowledge and underpin future studies investigating the kokumi sensation and the&#xD;
      mechanistic background of FAAA-conjugate effects. Moreover, food product reformulation with&#xD;
      the use of FAAA-conjugates could positively impact a wide range of consumers. Due to their&#xD;
      boosting sensory/hedonic effects, enriching foods with FAAA-conjugates has the potential to&#xD;
      reduce sugar, fat and salt content in a wide range of food products without compromising on&#xD;
      experienced flavour, thereby reducing sugar, fat and salt intake and their harmful effects.&#xD;
      More importantly, the elderly and seriously ill patients could benefit from the&#xD;
      palatability-enhancing effects ascribed to kokumi molecules, which could stimulate appetite&#xD;
      and help reverse weight loss (Witkamp, 2018).&#xD;
&#xD;
      2. OBJECTIVES&#xD;
&#xD;
      Primary Objective(s):&#xD;
&#xD;
      The primary objective of the current study is to determine if there is an objective&#xD;
      perceivable difference between plain and FAAA-enriched versions of selected food products and&#xD;
      describe sensory and/or hedonic differences between them, using a combination of&#xD;
      discrimination testing, descriptive analyses and hedonic tests.&#xD;
&#xD;
      Secondary Objective(s):&#xD;
&#xD;
      The secondary objective is to assess the dependency of FAAA-conjugates on the food matrix, by&#xD;
      separating administration of compound and product and assessing how separation affects&#xD;
      sensory and hedonic evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 9, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>A two-step, randomised controlled intervention study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>discrimination test</measure>
    <time_frame>90 minutes</time_frame>
    <description>percentage correctly identified FAAA-enriched samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>descriptive tests</measure>
    <time_frame>45 minutes</time_frame>
    <description>ratings sensory attributes on VAS-scales</description>
  </primary_outcome>
  <primary_outcome>
    <measure>hedonic test</measure>
    <time_frame>45 minutes</time_frame>
    <description>ratings product liking on VAS-scales</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Sensory Testing</condition>
  <arm_group>
    <arm_group_label>FAAA-enriched</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>food products enriched with FAAA-conjugates</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plain</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Food products without FAAA-conjugates</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>adding taste enhancer</intervention_name>
    <description>Comparing sensory profiles of food products either enriched with FAAA-conjugates or plain</description>
    <arm_group_label>FAAA-enriched</arm_group_label>
    <arm_group_label>Plain</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18-55 years&#xD;
&#xD;
          -  BMI: 18.0 - 27.0 kg/m2&#xD;
&#xD;
          -  Healthy (as judged by subject)&#xD;
&#xD;
          -  Consumer of products used in the study&#xD;
&#xD;
          -  Proficient in spoken and written English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Failure to meet any of the inclusion criteria&#xD;
&#xD;
          -  Weight loss or weight gain of 5 kg or more during the last 2 months&#xD;
&#xD;
          -  Regular smoker (&gt; 1 cigarette per day);&#xD;
&#xD;
          -  Restrained eater, assessed by the DEBQ (score of &gt;2.37 for men and &gt;3.24 for women&#xD;
             (van Strien, Frijters, Bergers, &amp; Defares, 1986))&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Anosmia or ageusia (self-reported)&#xD;
&#xD;
          -  Food allergies or intolerances relevant for the food products used in the experiment&#xD;
&#xD;
          -  Student/employee of the WUR Sensory Science and Eating Behaviour department&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerry Jager, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wageningen University, Division of Human Nutrition</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gerry Jager, PhD</last_name>
    <phone>+31317485850</phone>
    <email>gerry.jager@wur.nl</email>
  </overall_contact>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 24, 2018</study_first_submitted>
  <study_first_submitted_qc>December 24, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>December 24, 2018</last_update_submitted>
  <last_update_submitted_qc>December 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>taste enhancers</keyword>
  <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/NCT03787394
org study id: NL67908.081.18
nct id: NCT03787394
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Rationale: According to preliminary observations provided by the research and development
      department (R&D) of Givaudan, addition of specific fatty acid-amino acid (FAAA)-conjugates to
      a wide range of food products resulted in an enhancement of several sensory and hedonic
      effects. Such effects could be attributed to the so-called kokumi sensation, a taste concept
      that has been described as a "taste enhancer" that magnifies and lengthens all the other five
      basic tastes. The exact mechanisms of the kokumi sensation are as of yet unclear. Perception
      of the kokumi sensation depends on the context of other taste compounds and integration into
      food matrices. A systematic investigation is necessary to objectively evaluate whether the
      addition of specific FAAA-conjugates results in the enhancement of sensory and hedonic
      effects. Furthermore, we want to assess the dependency of these effects on the food matrix.
      To do so, a combination of discrimination, descriptive and hedonic testing will be carried
      out.

      Objectives: The primary objectives are: to determine if there is a perceivable difference
      between plain and FAAA-enriched versions of selected food products and describe sensory
      and/or hedonic differences between them; to assess the dependency of FAAA-conjugates on the
      food matrix.

      Study design: A two-step, randomised controlled intervention study will be carried out. Study
      population: 40 healthy, adult (18-55 years) males and females (BMI 18 - 27 kg/m2) from
      Wageningen and surroundings will be included.

      Intervention (if applicable): FAAA-conjugates: in step one, FAAA-conjugates will be
      integrated into food products; in step two, FAAA-conjugates will both be administered
      separately (using a tasteless mouthwash) and integrated into food products.

      Main study parameters/endpoints: The primary outcome parameters are: proportion of correct
      answers (discrimination testing); sensory evaluation score means (descriptive testing); and
      hedonic evaluation score means (hedonic testing).

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: The current study is non-therapeutic to subjects. Risks associated with
      participation are negligible and compared to other studies, the burden can be considered low.
      The FAAA-conjugates used in the intervention are declared "generally recognised as safe"
      (GRAS) by the Flavour Extract Manufacturers Association (FEMA) and pose no known adverse
      health effects.
FAAA conjugates are compounds containing different long-chain fatty acids and simple amino
      acids. They are involved in multiple signalling pathways playing a role in the regulation of
      homeostatic and non-homeostatic eating behaviour (Jager & Witkamp, 2014). FAAA-conjugates are
      naturally occurring in various animal and plant food sources, yet their dietary relevance and
      exact mechanism of action remains unclear. Notwithstanding, they have been related to
      improved food sensations and hedonic effects (Jager & Witkamp, 2014; Witkamp, 2018; Yoshida
      et al., 2013). FAAA compounds have been declared GRAS by FEMA, which guarantees their safe
      use in commercially available food products (Flavour Extract Manufacturers Association,
      2018).

      According to preliminary observations provided by the research and development department
      (R&D) of Givaudan, the addition of specific FAAA-conjugates to a range of food products
      resulted in an enhancement of several sensory- and hedonic effects in product evaluation.
      Panellists reported accentuated palatability; aftertaste masking; enhanced fat, sweet, salt
      and umami perception; and mouthfeel improvement. However, the reproducibility of these
      results is questionable, as substantial variation in the effects arose both within and
      between a small sample of volunteers. It is unclear whether these effects are specific for
      and dependent on integration of these conjugates in a certain food matrix, or if they have a
      more general boosting effect, relevant for taste or flavour. Perhaps the boosting effect also
      affects other sensory domains (e.g. vision).

      The aforementioned reported sensory/hedonic effects could be attributed to what has been
      described in literature as the kokumi sensation, which is related to activation of
      calcium-sensing receptors on the human tongue, albeit the exact mechanism remains to be
      elucidated (Feng, Zhang, Zhuang, Zhou, & Xu, 2016; Kuroda & Miyamura, 2015; Ohsu et al.,
      2010). Although Kokumi is associated with taste perception, it is most likely not a primary
      taste, since its effects exist in the context of other taste compounds. On their own, kokumi
      compounds elicit only very slight or no taste sensations but incorporated in a food matrix
      they can enhance other taste sensations. The threshold concentration of kokumi compounds in a
      plain water solution to induce a taste sensation is usually very high, while the threshold
      concentration in food to enhance other taste sensations can be very low. (Dunkel, Koster, &
      Hofmann, 2007; Feng et al., 2016; Kuroda & Miyamura, 2015).

      On the basis of preliminary testing done by R&D Givaudan, the study described in the current
      protocol aims to systematically investigate the sensory and hedonic effects of
      FAAA-conjugates. To do so, specific FAAA-conjugates will be integrated into two food products
      (one sweet (chocolate milk) and one savoury (salad dressing), which will be sensorially and
      hedonically evaluated. Furthermore, the dependency of FAAA-conjugates on the food matrix will
      be studied by administering them separately from food products. An untrained panel will be
      used, since consumers are not only capable of providing accurate and reliable information
      about product sensory characteristics, but can also serve as a measure of potential
      performance of the product in the marketplace (Ares & Varela, 2017; Lawless & Heymann, 2010).

      If results are in line with the aforementioned preliminary observations, they can add to the
      body of knowledge and underpin future studies investigating the kokumi sensation and the
      mechanistic background of FAAA-conjugate effects. Moreover, food product reformulation with
      the use of FAAA-conjugates could positively impact a wide range of consumers. Due to their
      boosting sensory/hedonic effects, enriching foods with FAAA-conjugates has the potential to
      reduce sugar, fat and salt content in a wide range of food products without compromising on
      experienced flavour, thereby reducing sugar, fat and salt intake and their harmful effects.
      More importantly, the elderly and seriously ill patients could benefit from the
      palatability-enhancing effects ascribed to kokumi molecules, which could stimulate appetite
      and help reverse weight loss (Witkamp, 2018).

      2. OBJECTIVES

      Primary Objective(s):

      The primary objective of the current study is to determine if there is an objective
      perceivable difference between plain and FAAA-enriched versions of selected food products and
      describe sensory and/or hedonic differences between them, using a combination of
      discrimination testing, descriptive analyses and hedonic tests.

      Secondary Objective(s):

      The secondary objective is to assess the dependency of FAAA-conjugates on the food matrix, by
      separating administration of compound and product and assessing how separation affects
      sensory and hedonic evaluation.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A two-step, randomised controlled intervention study
primary purpose: Basic Science
masking: Single (Participant)
measure: discrimination test
time frame: 90 minutes
description: percentage correctly identified FAAA-enriched samples
measure: descriptive tests
time frame: 45 minutes
description: ratings sensory attributes on VAS-scales
measure: hedonic test
time frame: 45 minutes
description: ratings product liking on VAS-scales
arm group label: FAAA-enriched
arm group type: Experimental
description: food products enriched with FAAA-conjugates
arm group label: Plain
arm group type: Placebo Comparator
description: Food products without FAAA-conjugates
intervention type: Other
intervention name: adding taste enhancer
description: Comparing sensory profiles of food products either enriched with FAAA-conjugates or plain
arm group label: FAAA-enriched
arm group label: Plain
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gerry Jager, PhD
role: Principal Investigator
affiliation: Wageningen University, Division of Human Nutrition
last name: Gerry Jager, PhD
phone: +31317485850
email: gerry.jager@wur.nl
responsible party type: Sponsor
sharing ipd: No