<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/NCT03037294</url>
  </required_header>
  <id_info>
    <org_study_id>16-3-036</org_study_id>
    <nct_id>NCT03037294</nct_id>
  </id_info>
  <brief_title>Protein Turnover in the Osteoarthritic Knee</brief_title>
  <acronym>KneeT</acronym>
  <official_title>Protein Turnover in the Osteoarthritic Knee; the Impact of Preoperative Protein Intake and Intra-articular Corticosteroid Injections</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>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Osteoarthritis (OA) of the knee is a common cause of pain and disability,&#xD;
      especially in people over the age of 65. In the current health care system both conservative&#xD;
      (e.g. intra-articular injections with corticosteroids) and surgical (total knee replacement,&#xD;
      TKR) treatment are applied. Although frequently used, certain effects of these treatments on&#xD;
      protein metabolism remain unclear. It is well known that maintenance of different tissues is&#xD;
      determined by a dynamic balance between protein synthesis and breakdown rates, with temporary&#xD;
      changes in either protein synthesis or breakdown allowing net protein accretion or loss.&#xD;
      Though protein supplementation has shown to be an effective nutritional strategy in&#xD;
      stimulating muscle protein synthesis, it remains unclear to what extent other musculoskeletal&#xD;
      tissues are able to respond to dietary protein supplementation. Therefore, the current study&#xD;
      assesses the impact of preoperative protein supplementation on protein synthesis in different&#xD;
      musculoskeletal tissues of the knee.&#xD;
&#xD;
      Objective: To investigate the effect of preoperative protein supplementation on Hoffa's fat&#xD;
      pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage protein synthesis of&#xD;
      the OA knee.&#xD;
&#xD;
      Study design: Randomized, parallel (two groups) study design. The intervention group will be&#xD;
      compared to the control group.&#xD;
&#xD;
      Study population: 24 adults with OA of the knee undergoing TKR. Intervention: Daily 40 g of&#xD;
      pre-sleep protein two weeks before TKR or no intervention.&#xD;
&#xD;
      Main study parameters/endpoints: Primary study parameters include protein synthesis rates and&#xD;
      enrichments of Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and&#xD;
      cartilage. Secondary parameters include whole-body protein synthesis, breakdown, oxidation,&#xD;
      and net balance.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: The risks involved in participating in this study are minimal. There are no&#xD;
      potential effects known for the ingestion of protein. Muscle biopsies and tissue collection&#xD;
      will be performed during the surgical procedure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in tissue-specific protein synthesis rates</measure>
    <time_frame>Throughout the surgical procedure (stable isotope methodology) and during the 2-week preoperative period (D2O dosing methodology).</time_frame>
    <description>Fractional synthetic rates calculated based on tissue-free, plasma, and protein-bound tracer enrichments using stable isotope methodology and D2O dosing methodology.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Osteo Arthritis Knee</condition>
  <condition>Protein Metabolism</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects in the control group will receive no intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Protein group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the protein group will receive a daily 40 g pre-sleep protein supplement during the 2-week preoperative period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Preoperative protein supplementation</intervention_name>
    <description>Daily 40 g of pre-sleep protein supplementation during 2-week preoperative period.</description>
    <arm_group_label>Protein group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Male and female patients scheduled for total knee arthroplasty&#xD;
&#xD;
          -  BMI between 18.5-30 kg/m2&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Mentally competent, as judged by the treating physician&#xD;
&#xD;
          -  Functioning gastrointestinal tract, eligible for oral protein supplementation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Corticosteroid injections less than 3 months prior to participation&#xD;
&#xD;
          -  Any medications know to affect protein metabolism (i.e. corticosteroids, non-steroidal&#xD;
             anti-inflammatories, or prescription strength acne medications)&#xD;
&#xD;
          -  Lactose intolerance&#xD;
&#xD;
          -  Insulin-dependent diabetes mellitus&#xD;
&#xD;
          -  Alcohol abuse&#xD;
&#xD;
          -  Rheumatoid arthritis&#xD;
&#xD;
          -  Peripheral artery disease Fontaine III or IV&#xD;
&#xD;
          -  COPD GOLD III or IV&#xD;
&#xD;
          -  Phenylketonuria&#xD;
&#xD;
          -  Surgical intervention in the past four weeks&#xD;
&#xD;
          -  Total parenteral nutrition at day of surgery&#xD;
&#xD;
          -  Neoadjuvant chemotherapy or radiotherapy&#xD;
&#xD;
          -  GFR &lt;20 mL/min/1.73 m2&#xD;
&#xD;
          -  Osteoarthritis of the knee secondary to septic arthritis, osteonecrosis, fracture, OD,&#xD;
             or malignant processes&#xD;
&#xD;
          -  Collagen disorders, e.g. Marfan and Ehler-Danlos&#xD;
&#xD;
          -  Any other medical condition that may interfere with the safety of the subjects or the&#xD;
             outcome parameters, in the investigators judgement&#xD;
&#xD;
          -  Investigator's uncertainty about the willingness or ability of the subject to comply&#xD;
             with the protocol instructions&#xD;
&#xD;
          -  Participation in any other studies involving investigational or marketed products&#xD;
             concomitantly or within two weeks prior to entry into the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Floris Hendriks, MSc, MD</last_name>
    <phone>+31655522347</phone>
    <email>f.hendriks@maastrichtuniversity.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joey Smeets</last_name>
    <email>joey.smeets@maastrichtuniversity.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <zip>6229ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joey Smeets, MSc, MD</last_name>
      <phone>+31651363946</phone>
      <email>joey.smeets@maastrichtuniversity.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>May 2, 2022</last_update_submitted>
  <last_update_submitted_qc>May 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Maastricht University Medical Center</investigator_affiliation>
    <investigator_full_name>Lex Verdijk</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <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/NCT03037294
org study id: 16-3-036
nct id: NCT03037294
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Rationale: Osteoarthritis (OA) of the knee is a common cause of pain and disability,
      especially in people over the age of 65. In the current health care system both conservative
      (e.g. intra-articular injections with corticosteroids) and surgical (total knee replacement,
      TKR) treatment are applied. Although frequently used, certain effects of these treatments on
      protein metabolism remain unclear. It is well known that maintenance of different tissues is
      determined by a dynamic balance between protein synthesis and breakdown rates, with temporary
      changes in either protein synthesis or breakdown allowing net protein accretion or loss.
      Though protein supplementation has shown to be an effective nutritional strategy in
      stimulating muscle protein synthesis, it remains unclear to what extent other musculoskeletal
      tissues are able to respond to dietary protein supplementation. Therefore, the current study
      assesses the impact of preoperative protein supplementation on protein synthesis in different
      musculoskeletal tissues of the knee.

      Objective: To investigate the effect of preoperative protein supplementation on Hoffa's fat
      pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage protein synthesis of
      the OA knee.

      Study design: Randomized, parallel (two groups) study design. The intervention group will be
      compared to the control group.

      Study population: 24 adults with OA of the knee undergoing TKR. Intervention: Daily 40 g of
      pre-sleep protein two weeks before TKR or no intervention.

      Main study parameters/endpoints: Primary study parameters include protein synthesis rates and
      enrichments of Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and
      cartilage. Secondary parameters include whole-body protein synthesis, breakdown, oxidation,
      and net balance.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: The risks involved in participating in this study are minimal. There are no
      potential effects known for the ingestion of protein. Muscle biopsies and tissue collection
      will be performed during the surgical procedure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Change in tissue-specific protein synthesis rates
time frame: Throughout the surgical procedure (stable isotope methodology) and during the 2-week preoperative period (D2O dosing methodology).
description: Fractional synthetic rates calculated based on tissue-free, plasma, and protein-bound tracer enrichments using stable isotope methodology and D2O dosing methodology.
arm group label: Control group
arm group type: No Intervention
description: Subjects in the control group will receive no intervention.
arm group label: Protein group
arm group type: Experimental
description: Subjects in the protein group will receive a daily 40 g pre-sleep protein supplement during the 2-week preoperative period.
intervention type: Dietary Supplement
intervention name: Preoperative protein supplementation
description: Daily 40 g of pre-sleep protein supplementation during 2-week preoperative period.
arm group label: Protein group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Floris Hendriks, MSc, MD
phone: +31655522347
email: f.hendriks@maastrichtuniversity.nl
last name: Joey Smeets
email: joey.smeets@maastrichtuniversity.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Maastricht University Medical Center
investigator full name: Lex Verdijk
investigator title: Assistant Professor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
sharing ipd: No