<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/NCT03769857</url>
  </required_header>
  <id_info>
    <org_study_id>ESM-CLN#2019T01</org_study_id>
    <nct_id>NCT03769857</nct_id>
  </id_info>
  <brief_title>NEM® + BIOCURC® Versus Placebo in Exercised-induced Joint Pain, Stiffness, &amp; Cartilage Turnover in Healthy Men &amp; Women</brief_title>
  <official_title>Efficacy of NEM® Brand Eggshell Membrane Plus BIOCURC® Brand Bioavailable Curcumin Versus Placebo in Exercised-induced Joint Pain, Stiffness, &amp; Cartilage Turnover in Healthy Men &amp; Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ESM Technologies, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>QPS Bio-Kinetic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ESM Technologies, LLC</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 intended to evaluate the combined effects of the dietary supplement NEM® brand&#xD;
      eggshell membrane and BIOCURC® brand bioavailable curcumin versus placebo in reducing&#xD;
      exercise-induced joint pain, stiffness &amp; cartilage turnover in healthy men &amp; women. Half of&#xD;
      the study participants will receive NEM+BIOCURC, once daily, orally while the other half of&#xD;
      the study participants will receive placebo, once daily, orally while performing an exercise&#xD;
      regimen every other day for two weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Moderate exercise can induce discomfort in joints when done infrequently or when done too&#xD;
      intensely or for too long a period. This discomfort is often realized as either pain or&#xD;
      stiffness in the joint that was the focus of the exercise. For example, one's knees will hurt&#xD;
      after jogging for several miles, particularly if jogging for the first time. This study is&#xD;
      intended to evaluate whether the combination of NEM® brand eggshell membrane and BIOCURC®&#xD;
      brand bioavailable curcumin can alleviate joint pain or stiffness, either directly following&#xD;
      exercise or 12 hours post-exercise versus placebo. The study will also evaluate the&#xD;
      combination's effect, on cartilage turnover via the cartilage degradation biomarker&#xD;
      c-terminal cross-linked telopeptide of type II collagen (CTX-II). Participants will perform a&#xD;
      minimum of 50 steps per leg utilizing an aerobics step at the clinical site. They will follow&#xD;
      this exercise regimen on alternating days for 2 consecutive weeks. Changes in pain &amp;&#xD;
      stiffness (immediate &amp; 12-hour) will be compared to both baseline and to the placebo group.&#xD;
      Urine samples will also be collected at baseline and at the end of Week 1 &amp; Week 2. The&#xD;
      change in CTX-II from baseline will be compared to the placebo group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 13, 2019</start_date>
  <completion_date type="Actual">April 15, 2019</completion_date>
  <primary_completion_date type="Actual">February 20, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>treatment versus placebo</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Quadruple Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise-induced Cartilage Turnover via CTX-II Biomarker</measure>
    <time_frame>2 Weeks</time_frame>
    <description>To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced cartilage turnover in healthy men &amp; women by evaluating the change in urinary CTX-II levels.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exercise-induced Joint Pain via questionnaire</measure>
    <time_frame>2 Weeks</time_frame>
    <description>To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced knee discomfort (pain/aching) based upon perceived pain rated on a 0-10 point continuous scale (where 0 = no pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise-induced Joint Stiffness via questionnaire</measure>
    <time_frame>2 Weeks</time_frame>
    <description>To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced knee stiffness based upon perceived stiffness rated on a 0-10 point continuous scale (where 0 = no stiffness).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Exercise-induced Joint Pain</condition>
  <condition>Exercise-induced Joint Stiffness</condition>
  <condition>Exercise-induced Joint Cartilage Turnover</condition>
  <arm_group>
    <arm_group_label>NEM® + BIOCURC®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NEM® + BIOCURC®&#xD;
NEM, 500 mg, #0 capsule, once daily orally for 2 weeks PLUS BIOCURC, 350 mg, #10 oval softgel, once daily orally for 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, 500 mg, #0 capsule, once daily orally for 2 weeks PLUS Placebo, 350 mg, #10 oval softgel, once daily orally for 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>NEM® + BIOCURC®</intervention_name>
    <description>Dietary supplement combination for the support of joint health.</description>
    <arm_group_label>NEM® + BIOCURC®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or Female subjects must be 40-75 years of age at the time of Screening.&#xD;
&#xD;
          2. Subjects must not have been diagnosed with a JCT disease (i.e. osteoarthritis,&#xD;
             rheumatoid arthritis, spondyloarthritis, bursitis, gout, systemic lupus erythematosus,&#xD;
             fibromyalgia, etc.) affecting the hip, knee, or ankle by a licensed physician prior to&#xD;
             enrollment evaluation / screening.&#xD;
&#xD;
          3. Subjects must have a resting pain/discomfort score of ≤ 2 on the 10-point continuous&#xD;
             scale in the knee with the most severe pain/discomfort at the Follow-Up&#xD;
             Screening/Baseline (first exercise visit).&#xD;
&#xD;
          4. Subjects must be willing and healthy enough, as judged by the clinical Investigator or&#xD;
             Sub-Investigator(s), to perform moderate exercise.&#xD;
&#xD;
          5. Subjects must be available for and willing to attend all evaluation visits.&#xD;
&#xD;
          6. Subjects must be able and willing to give informed consent.&#xD;
&#xD;
          7. Subjects must be willing to use only acetaminophen as rescue pain medication, if&#xD;
             needed.&#xD;
&#xD;
          8. Subjects participating in prior studies evaluating eggshell membrane, curcumin, fish&#xD;
             oil or collagen can participate in the present study so long as they are not currently&#xD;
             taking an eggshell membrane, fish oil, curcumin, or collagen supplement and have not&#xD;
             done so for 60 days prior to screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject is currently receiving therapy with remission-inducing drugs (i.e.&#xD;
             methotrexate, TNF biologics, etc.), immunosuppressive drugs (i.e. corticosteroids,&#xD;
             transplantation medications, etc.) or planning to use these products during the study&#xD;
             period.&#xD;
&#xD;
          2. Subject has been diagnosed with any clinically significant confounding inflammatory&#xD;
             disease or condition that would interfere with the study evaluation, as judged by the&#xD;
             clinical investigator (i.e. pseudo gout, Paget's disease, chronic pain syndrome,&#xD;
             active rheumatic fever, etc.).&#xD;
&#xD;
          3. Subject has known allergy to any of the investigational products, including but not&#xD;
             limited to eggs or egg products and rice or rice flour. If any subject becomes&#xD;
             sensitive during the study, they will immediately be excluded from continuing in the&#xD;
             study.&#xD;
&#xD;
          4. Subject suffers from clinically significant cardiac, pulmonary, or other complications&#xD;
             that would prevent them from performing moderate exercise or could pose a risk to the&#xD;
             subject's health, as judged by the clinical investigator.&#xD;
&#xD;
          5. Subject participates in activities involving intensive use of the lower extremities&#xD;
             (i.e. running / jogging, sports, bicycling, dancing, etc.) 2 or more days per week or&#xD;
             participates in activities that involve moderate use of the lower extremities (i.e.&#xD;
             walking, golfing, yoga, etc.) 3 or more days per week.&#xD;
&#xD;
          6. Subject's body weight is greater than 300 pounds (136.1 kg) at the time of Screening.&#xD;
&#xD;
          7. Subject is currently taking or is unwilling to forgo the use of prescription,&#xD;
             over-the-counter (OTC) treatments, and/or dietary supplements affecting joint health&#xD;
             within 30 days prior to baseline evaluation and for the duration of the study.&#xD;
             Prohibited medications include: NSAIDs, analgesics (other than acetaminophen),&#xD;
             opioids, anti-depressants (of all drug classes for this indication, including but not&#xD;
             limited to SSRI's such as citalopram and fluoxetine, TCA's such as amitriptyline and&#xD;
             amoxapine, SNRI's such as duloxetine or SNRI's used for fibromyalgia such as&#xD;
             milnacipran and NDRI's such as bupropion), other medications for the management of&#xD;
             painful conditions (i.e. fibromyalgia) including gabapentin and tizanidine &amp; joint&#xD;
             supplements. Examples of these types of medications are: aspirin, ibuprofen, naproxen,&#xD;
             oxycodone, propoxyphene, diclofenac, celecoxib, amitriptyline, duloxetine,&#xD;
             glucosamine, chondroitin, MSM, white willow bark, turmeric or curcumin, Boswellia,&#xD;
             fish oil, etc.&#xD;
&#xD;
             a. Washout Periods: Subjects are eligible to participate in the study following a&#xD;
             7-day washout period for opioids, a 14-day washout period for analgesics &amp; NSAIDs, and&#xD;
             a 90-day washout period for steroids, anti-depressants, or JCT dietary supplements&#xD;
             (i.e. glucosamine, chondroitin, MSM, etc.) Acetaminophen must not have been taken&#xD;
             within 24 hours of the first baseline evaluation.&#xD;
&#xD;
          8. Subject is involved in any other research study involving an investigational product&#xD;
             (drug, device or biologic) or a new application of an approved product, within 30 days&#xD;
             of the first baseline evaluation.&#xD;
&#xD;
          9. Pregnant and breastfeeding women, or women who intend to become pregnant during the&#xD;
             course of the study.&#xD;
&#xD;
         10. Subject has a history or positive test result of HIV, hepatitis B or hepatitis C.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Ruff, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>ESM Technologies, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>QPS Bio-Kinetic</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65802</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>exercise-induced</keyword>
  <keyword>joint pain</keyword>
  <keyword>joint stiffness</keyword>
  <keyword>cartilage turnover</keyword>
  <keyword>CTX-II</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthralgia</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/NCT03769857
org study id: ESM-CLN#2019T01
nct id: NCT03769857
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is intended to evaluate the combined effects of the dietary supplement NEM® brand
      eggshell membrane and BIOCURC® brand bioavailable curcumin versus placebo in reducing
      exercise-induced joint pain, stiffness & cartilage turnover in healthy men & women. Half of
      the study participants will receive NEM+BIOCURC, once daily, orally while the other half of
      the study participants will receive placebo, once daily, orally while performing an exercise
      regimen every other day for two weeks.
Moderate exercise can induce discomfort in joints when done infrequently or when done too
      intensely or for too long a period. This discomfort is often realized as either pain or
      stiffness in the joint that was the focus of the exercise. For example, one's knees will hurt
      after jogging for several miles, particularly if jogging for the first time. This study is
      intended to evaluate whether the combination of NEM® brand eggshell membrane and BIOCURC®
      brand bioavailable curcumin can alleviate joint pain or stiffness, either directly following
      exercise or 12 hours post-exercise versus placebo. The study will also evaluate the
      combination's effect, on cartilage turnover via the cartilage degradation biomarker
      c-terminal cross-linked telopeptide of type II collagen (CTX-II). Participants will perform a
      minimum of 50 steps per leg utilizing an aerobics step at the clinical site. They will follow
      this exercise regimen on alternating days for 2 consecutive weeks. Changes in pain &
      stiffness (immediate & 12-hour) will be compared to both baseline and to the placebo group.
      Urine samples will also be collected at baseline and at the end of Week 1 & Week 2. The
      change in CTX-II from baseline will be compared to the placebo group.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: treatment versus placebo
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Quadruple Blind
measure: Exercise-induced Cartilage Turnover via CTX-II Biomarker
time frame: 2 Weeks
description: To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced cartilage turnover in healthy men & women by evaluating the change in urinary CTX-II levels.
measure: Exercise-induced Joint Pain via questionnaire
time frame: 2 Weeks
description: To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced knee discomfort (pain/aching) based upon perceived pain rated on a 0-10 point continuous scale (where 0 = no pain).
measure: Exercise-induced Joint Stiffness via questionnaire
time frame: 2 Weeks
description: To evaluate the efficacy of NEM®+BIOCURC® versus placebo at reducing exercise-induced knee stiffness based upon perceived stiffness rated on a 0-10 point continuous scale (where 0 = no stiffness).
arm group label: NEM® + BIOCURC®
arm group type: Experimental
description: NEM® + BIOCURC®
NEM, 500 mg, #0 capsule, once daily orally for 2 weeks PLUS BIOCURC, 350 mg, #10 oval softgel, once daily orally for 2 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, 500 mg, #0 capsule, once daily orally for 2 weeks PLUS Placebo, 350 mg, #10 oval softgel, once daily orally for 2 weeks
intervention type: Dietary Supplement
intervention name: NEM® + BIOCURC®
description: Dietary supplement combination for the support of joint health.
arm group label: NEM® + BIOCURC®
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kevin Ruff, Ph.D.
role: Study Chair
affiliation: ESM Technologies, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Arthralgia
sharing ipd: No