<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/NCT01680146</url>
  </required_header>
  <id_info>
    <org_study_id>METC 12-3-030</org_study_id>
    <nct_id>NCT01680146</nct_id>
  </id_info>
  <brief_title>Impact of Fat Co-ingestion With Protein on the Post-prandial Anabolic Response in Elderly Men</brief_title>
  <acronym>Pro-Fat</acronym>
  <official_title>Impact of Fat Co-ingestion With Protein on the Post-prandial Anabolic Response in Elderly Men (Pro-Fat Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a&#xD;
      major impact on our healthcare system due to increased morbidity and greater need for&#xD;
      hospitalization and/or institutionalization. One way to prevent skeletal muscle loss is to&#xD;
      improve dietary intake of the elderly. It has already been shown that ingestion of dietary&#xD;
      protein stimulates muscle protein synthesis and inhibits muscle protein breakdown, resulting&#xD;
      in an overall positive net protein balance. However, the impact of fat (as part of the meal)&#xD;
      on dietary protein-induced muscle protein synthesis remains largely unknown. Based on&#xD;
      previous studies by other research groups, we hypothesize that fat further stimulates the&#xD;
      muscle anabolic response to protein ingestion.&#xD;
&#xD;
      Objective: The primary objective of this study is to investigate the effect of a single&#xD;
      meal-like amount of protein with or without fat on postprandial muscle protein synthesis&#xD;
      rates in healthy elderly men. Furthermore, as a secondary objective, we will assess digestion&#xD;
      and absorption kinetics.&#xD;
&#xD;
      Study design: double-blind randomized intervention study Study population: 24 healthy elderly&#xD;
      men (55-85 y) Intervention: one group (n=12) will consume a test beverage of 350 mL&#xD;
      containing 20 g of intrinsically labeled casein, and the other group (n=12) will consume a&#xD;
      beverage of the same volume containing 20 g of casein plus 20 g of fat.&#xD;
&#xD;
      Main study parameters/endpoints: Primary endpoint: muscle protein synthesis rates. Secondary&#xD;
      endpoint: digestion and absorption kinetics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a major impact on&#xD;
      our healthcare system due to increased morbidity and greater need for hospitalization and/or&#xD;
      institutionalization. The age-related loss of skeletal muscle mass is facilitated by a&#xD;
      combination of factors, which include a less than optimal diet and a sedentary lifestyle.&#xD;
      These factors contribute to a disruption in the regulation of skeletal muscle protein&#xD;
      turnover, leading to an imbalance between muscle protein synthesis (MPS) and degradation. One&#xD;
      way to overcome this problem is to improve dietary intake of the elderly. It has been well&#xD;
      established that nutrient intake greatly affects protein turnover in skeletal muscle tissue.&#xD;
&#xD;
      Ingestion of dietary protein stimulates MPS rates and inhibits muscle protein breakdown&#xD;
      rates, resulting in an overall positive net protein balance in both the young and elderly.&#xD;
      However, it is not clear what the impact is of co-ingestion of other macronutrients on&#xD;
      digestion and absorption kinetics or MPS rates in the healthy young or the elderly. We have&#xD;
      recently conducted a study to examine the impact of carbohydrate co-ingestion on postprandial&#xD;
      MPS in the healthy young and old. Indeed, preliminary results show that carbohydrate&#xD;
      co-ingestion stimulates protein synthesis.&#xD;
&#xD;
      Interestingly, very little is known about the impact of fat co-ingestion with protein on the&#xD;
      stimulation of post-prandial MPS rates. What is noteworthy is that Elliot et al. investigated&#xD;
      the effect of whole milk ingestion on net muscle protein balance after resistance exercise&#xD;
      using an arteriovenous balance approach. Ingestion of whole milk (containing 50 en% fats)&#xD;
      stimulated the post-exercise net uptake of phenylalanine and threonine to a greater extent&#xD;
      than ingestion of fat-free milk (containing 6 en% fat). Although, amino acid uptake is&#xD;
      indicative of 'muscle anabolism', it is not a direct measure of MPS so no firm conclusions&#xD;
      can be deduce from this work. Furthermore, milk also contains a certain amount of&#xD;
      carbohydrates (fat-free milk 55 en% and whole milk 30 en%), which does not allow for direct&#xD;
      assessment of fat co-ingestion per se.&#xD;
&#xD;
      Certainly, other studies have investigated the effect of long term fatty acid intake, using&#xD;
      direct incorporation methods, on the MPS rates. For example, long term omega-3&#xD;
      polyunsaturated fatty acid (n-3 PUFA) supplementation increased feeding-mediated MPS rates in&#xD;
      young, middle-aged, and older adults. The mechanism(s) underpinning the enhanced effect of&#xD;
      n-3 PUFA supplementation on post-prandial MPS rates to dietary protein are not well defined.&#xD;
      It has been speculated that the enhanced feeding-effect of n-3 PUFA on postprandial MPS rates&#xD;
      is due to remodeling of the sarcolemma to include a greater n-3 PUFA content, and ultimately&#xD;
      enhances insulin's action on muscle protein metabolism. This is clearly a long term effect,&#xD;
      but what about the acute effects of fat co-ingestion on postprandial MPS rates? Katsanos et&#xD;
      al. found that elevated plasma fatty acid concentrations did not interfere with the&#xD;
      post-prandial stimulation of MPS. However, subjects ingested a single bolus of essential&#xD;
      amino acids while receiving fatty acid infusion, which clearly does not reflect a 'real&#xD;
      world' setting. In the end, there is reason to believe that the presence of fat in a meal&#xD;
      further stimulates the muscle anabolic response to meal ingestion. However, fat intake may&#xD;
      also modulate gastric emptying and dietary protein digestion and absorption kinetics. To&#xD;
      date, the acute (not long-term supplementation) impact of fat in a meal on post-prandial&#xD;
      muscle protein anabolism and digestion and absorption kinetics remains completely unexplored,&#xD;
      and thus we can only speculate on the impact that fat co-ingestion has on postprandial MPS&#xD;
      rates.&#xD;
&#xD;
      In the present study we will investigate the effect of a single meal-like amount of protein&#xD;
      with or without fat on postprandial MPS in healthy elderly men. Furthermore, we will assess&#xD;
      digestion and absorption kinetics. The use of intrinsically labeled casein will allows us&#xD;
      determine de novo MPS from amino acids that come available through the test beverage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>muscle protein synthesis (MPS) rates</measure>
    <time_frame>1 day</time_frame>
    <description>The main study endpoint is muscle protein synthesis (MPS) rates. In order to determine the MPS, the following parameters will be measured:&#xD;
Muscle protein-bound L-[1-13C]-phenylalanine, L-[ring-2H5]-phenylalanine, and L-[1-13C]-leucine enrichment (expressed as MPE)&#xD;
Plasma L-[1-13C]-phenylalanine and L-[1-13C]-KIC enrichment (expressed as MPE)&#xD;
Muscle free (intracellular) L-[1-13C]-phenylalanine enrichment (expressed as MPE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>protein digestion and absorption kinetics</measure>
    <time_frame>1 day</time_frame>
    <description>Secondary endpoints include protein digestion and absorption kinetics. Therefore, the following parameters will be measured:&#xD;
Plasma phenylalanine, tyrosine, and leucine concentration (expressed as μmol/L)&#xD;
Plasma enrichments of:&#xD;
L-[1-13C]-phenylalanine&#xD;
L-[1-13C]-tyrosine&#xD;
L-[1-13C]-leucine&#xD;
L-[ring-2H5]-phenylalanine&#xD;
L-[ring-2H4]-tyrosine&#xD;
L-[ring-2H2]-tyrosine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>whole-body protein metabolism</measure>
    <time_frame>1 day</time_frame>
    <description>Secondary endpoints include whole-body protein metabolism, which will be calculated based on protein digestion and absorption kinetics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose concentrations</measure>
    <time_frame>1 day</time_frame>
    <description>During the experimental trial, we will measure glucose concentrations in the obtained plasma samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin concentrations</measure>
    <time_frame>1 day</time_frame>
    <description>During the experimental trial, we will measure insulin concentrations in the obtained plasma samples.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Sarcopenia</condition>
  <arm_group>
    <arm_group_label>PRO</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will ingest 20 g of intrinsically labeled casein dissolved in water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PRO+FAT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will ingest 20 g of intrinsically labeled casein plus 26.7 g of anhydrous milk fat dissolved in water</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PRO+FAT</intervention_name>
    <arm_group_label>PRO+FAT</arm_group_label>
    <other_name>20 g of casein + 26.7 g Anhydrous Milk Fat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PRO</intervention_name>
    <arm_group_label>PRO</arm_group_label>
    <other_name>20 g of casein</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males&#xD;
&#xD;
          -  Age between 55 and 85&#xD;
&#xD;
          -  BMI &lt; 30 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Glucose intolerance&#xD;
&#xD;
          -  Milk and/or fat intolerance&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Diagnosed GI tract diseases&#xD;
&#xD;
          -  Arthritic conditions&#xD;
&#xD;
          -  A history of neuromuscular problems&#xD;
&#xD;
          -  Any medications known to affect protein metabolism (i.e. corticosteroids,&#xD;
             non-steroidal anti-inflammatories, or prescription strength acne medications).&#xD;
&#xD;
          -  Use of anticoagulants&#xD;
&#xD;
          -  Participation in exercise program&#xD;
&#xD;
          -  Hypertension, high blood pressure that is above 140/90 mmHg.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luc JC van Loon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6200 MD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://www.m3-research.nl</url>
    <description>Research group website</description>
  </link>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>November 27, 2014</last_update_submitted>
  <last_update_submitted_qc>November 27, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcopenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Caseins</mesh_term>
  </intervention_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/NCT01680146
org study id: METC 12-3-030
nct id: NCT01680146
lead sponsor: 
has dmc: No
Rationale: The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a
      major impact on our healthcare system due to increased morbidity and greater need for
      hospitalization and/or institutionalization. One way to prevent skeletal muscle loss is to
      improve dietary intake of the elderly. It has already been shown that ingestion of dietary
      protein stimulates muscle protein synthesis and inhibits muscle protein breakdown, resulting
      in an overall positive net protein balance. However, the impact of fat (as part of the meal)
      on dietary protein-induced muscle protein synthesis remains largely unknown. Based on
      previous studies by other research groups, we hypothesize that fat further stimulates the
      muscle anabolic response to protein ingestion.

      Objective: The primary objective of this study is to investigate the effect of a single
      meal-like amount of protein with or without fat on postprandial muscle protein synthesis
      rates in healthy elderly men. Furthermore, as a secondary objective, we will assess digestion
      and absorption kinetics.

      Study design: double-blind randomized intervention study Study population: 24 healthy elderly
      men (55-85 y) Intervention: one group (n=12) will consume a test beverage of 350 mL
      containing 20 g of intrinsically labeled casein, and the other group (n=12) will consume a
      beverage of the same volume containing 20 g of casein plus 20 g of fat.

      Main study parameters/endpoints: Primary endpoint: muscle protein synthesis rates. Secondary
      endpoint: digestion and absorption kinetics.
The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a major impact on
      our healthcare system due to increased morbidity and greater need for hospitalization and/or
      institutionalization. The age-related loss of skeletal muscle mass is facilitated by a
      combination of factors, which include a less than optimal diet and a sedentary lifestyle.
      These factors contribute to a disruption in the regulation of skeletal muscle protein
      turnover, leading to an imbalance between muscle protein synthesis (MPS) and degradation. One
      way to overcome this problem is to improve dietary intake of the elderly. It has been well
      established that nutrient intake greatly affects protein turnover in skeletal muscle tissue.

      Ingestion of dietary protein stimulates MPS rates and inhibits muscle protein breakdown
      rates, resulting in an overall positive net protein balance in both the young and elderly.
      However, it is not clear what the impact is of co-ingestion of other macronutrients on
      digestion and absorption kinetics or MPS rates in the healthy young or the elderly. We have
      recently conducted a study to examine the impact of carbohydrate co-ingestion on postprandial
      MPS in the healthy young and old. Indeed, preliminary results show that carbohydrate
      co-ingestion stimulates protein synthesis.

      Interestingly, very little is known about the impact of fat co-ingestion with protein on the
      stimulation of post-prandial MPS rates. What is noteworthy is that Elliot et al. investigated
      the effect of whole milk ingestion on net muscle protein balance after resistance exercise
      using an arteriovenous balance approach. Ingestion of whole milk (containing 50 en% fats)
      stimulated the post-exercise net uptake of phenylalanine and threonine to a greater extent
      than ingestion of fat-free milk (containing 6 en% fat). Although, amino acid uptake is
      indicative of 'muscle anabolism', it is not a direct measure of MPS so no firm conclusions
      can be deduce from this work. Furthermore, milk also contains a certain amount of
      carbohydrates (fat-free milk 55 en% and whole milk 30 en%), which does not allow for direct
      assessment of fat co-ingestion per se.

      Certainly, other studies have investigated the effect of long term fatty acid intake, using
      direct incorporation methods, on the MPS rates. For example, long term omega-3
      polyunsaturated fatty acid (n-3 PUFA) supplementation increased feeding-mediated MPS rates in
      young, middle-aged, and older adults. The mechanism(s) underpinning the enhanced effect of
      n-3 PUFA supplementation on post-prandial MPS rates to dietary protein are not well defined.
      It has been speculated that the enhanced feeding-effect of n-3 PUFA on postprandial MPS rates
      is due to remodeling of the sarcolemma to include a greater n-3 PUFA content, and ultimately
      enhances insulin's action on muscle protein metabolism. This is clearly a long term effect,
      but what about the acute effects of fat co-ingestion on postprandial MPS rates? Katsanos et
      al. found that elevated plasma fatty acid concentrations did not interfere with the
      post-prandial stimulation of MPS. However, subjects ingested a single bolus of essential
      amino acids while receiving fatty acid infusion, which clearly does not reflect a 'real
      world' setting. In the end, there is reason to believe that the presence of fat in a meal
      further stimulates the muscle anabolic response to meal ingestion. However, fat intake may
      also modulate gastric emptying and dietary protein digestion and absorption kinetics. To
      date, the acute (not long-term supplementation) impact of fat in a meal on post-prandial
      muscle protein anabolism and digestion and absorption kinetics remains completely unexplored,
      and thus we can only speculate on the impact that fat co-ingestion has on postprandial MPS
      rates.

      In the present study we will investigate the effect of a single meal-like amount of protein
      with or without fat on postprandial MPS in healthy elderly men. Furthermore, we will assess
      digestion and absorption kinetics. The use of intrinsically labeled casein will allows us
      determine de novo MPS from amino acids that come available through the test beverage.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: muscle protein synthesis (MPS) rates
time frame: 1 day
description: The main study endpoint is muscle protein synthesis (MPS) rates. In order to determine the MPS, the following parameters will be measured:
Muscle protein-bound L-[1-13C]-phenylalanine, L-[ring-2H5]-phenylalanine, and L-[1-13C]-leucine enrichment (expressed as MPE)
Plasma L-[1-13C]-phenylalanine and L-[1-13C]-KIC enrichment (expressed as MPE)
Muscle free (intracellular) L-[1-13C]-phenylalanine enrichment (expressed as MPE)
measure: protein digestion and absorption kinetics
time frame: 1 day
description: Secondary endpoints include protein digestion and absorption kinetics. Therefore, the following parameters will be measured:
Plasma phenylalanine, tyrosine, and leucine concentration (expressed as μmol/L)
Plasma enrichments of:
L-[1-13C]-phenylalanine
L-[1-13C]-tyrosine
L-[1-13C]-leucine
L-[ring-2H5]-phenylalanine
L-[ring-2H4]-tyrosine
L-[ring-2H2]-tyrosine
measure: whole-body protein metabolism
time frame: 1 day
description: Secondary endpoints include whole-body protein metabolism, which will be calculated based on protein digestion and absorption kinetics.
measure: Glucose concentrations
time frame: 1 day
description: During the experimental trial, we will measure glucose concentrations in the obtained plasma samples.
measure: Insulin concentrations
time frame: 1 day
description: During the experimental trial, we will measure insulin concentrations in the obtained plasma samples.
arm group label: PRO
arm group type: Active Comparator
description: Subjects will ingest 20 g of intrinsically labeled casein dissolved in water
arm group label: PRO+FAT
arm group type: Experimental
description: Subjects will ingest 20 g of intrinsically labeled casein plus 26.7 g of anhydrous milk fat dissolved in water
intervention type: Dietary Supplement
intervention name: PRO+FAT
arm group label: PRO+FAT
other name: 20 g of casein + 26.7 g Anhydrous Milk Fat
intervention type: Dietary Supplement
intervention name: PRO
arm group label: PRO
other name: 20 g of casein
criteria: 
gender: Male
minimum age: 55 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Luc JC van Loon, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
url: http://www.m3-research.nl
description: Research group website
responsible party type: Sponsor
mesh term: Sarcopenia
mesh term: Caseins