<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/NCT04499963</url>
  </required_header>
  <id_info>
    <org_study_id>pro00103700</org_study_id>
    <nct_id>NCT04499963</nct_id>
  </id_info>
  <brief_title>Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS)</brief_title>
  <official_title>An Open-label, Single-center, 6-month Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Richard Bedlack, M.D., Ph.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial&#xD;
      utilizing a historical control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial&#xD;
      utilizing a historical control group. Following informed consent and screening, participants&#xD;
      with ALS will take Theracurmin 1 capsule (90mg) twice daily for 6-months. Treatment with the&#xD;
      Theracurmin and all study outcome measures and labs are being performed exclusively for&#xD;
      research purposes. Collected data includes saliva and stool microbiome sampling, adverse&#xD;
      events, concomitant medications, weight and height, Theracurmin treatment evaluations, and&#xD;
      Thrive Questionnaires. Participants will be asked to register on the website Patientslikeme.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2020</start_date>
  <completion_date type="Actual">August 30, 2022</completion_date>
  <primary_completion_date type="Actual">August 30, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This will be a 6-month, widely inclusive, largely remote/virtual, single-center, open-label pilot trial utilizing a historical control group.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ALSFRS-R score</measure>
    <time_frame>Starting at week 4 and then once every 30 days for 6 months</time_frame>
    <description>The ALSFRS-R (ALS Functional Rating Scale-Revised) will be determined at all video/telephone visits. ALSFRS-R is a quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ALS Reversals</measure>
    <time_frame>month 6</time_frame>
    <description>To look for an increase in the frequency of ALS reversals, we will count the number of participants who have an ALSFRS-R score that improves by 4 points or more over 6 months. The observed frequency of spontaneous ALS reversals defined in this way is 2-5% (30). We will look for an increase in this frequency to at least 10% (1 in 10).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva Microbiome Sequencing change</measure>
    <time_frame>Enrollment, week 4 and month 6 visits</time_frame>
    <description>The microbiome of study participants will be analyzed in saliva samples at enrollment, week 4 and month 6 visits. We will compare the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls.Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events as measured by patient reporting</measure>
    <time_frame>Study duration, up to 6 months</time_frame>
    <description>Adverse and serious adverse events will be recorded throughout the study. The PI will determine whether these are related to treatment. Patients will also measure and record their side effects at Month 0-6 Internet Visits on their PLM profile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Enrollment Rate</measure>
    <time_frame>one month</time_frame>
    <description>Enrollment rate will be calculated as the number of participants enrolled per month.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retention</measure>
    <time_frame>month 6</time_frame>
    <description>Retention will be assessed by looking at the dropout rate at 6 months (the percentage of surviving enrolled patients who complete the Month 6 Visit).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool Microbiome Sequencing change</measure>
    <time_frame>Enrollment, week 4 and month 6 visits</time_frame>
    <description>The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Metagenomic analysis of deidentified selected fecal sample will be done on patients that positively respond to Theracurmin to achieve strain level identification of microbes positively and negatively associated with improved outcomes. The selected anaerobes that have been linked to ALS severity will be cultured for further genetic sand phenotypic characterization.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Open Label Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention is twice daily dosage of Theracurmin 90 mg capsules. This same dose was used in a successful trial of patients with mild cognitive impairment. Theracurmin HP capsules containing 90 mg curcumin each that will be taken as one capsule twice daily for 6 months. Each capsule contains 300 mg Theracurmin enhanced bioavailable water-dispersible turmeric rhizome complex providing 30% curcumin (90 mg). The content of Theracurmin HP has been independently certified by NSF International under NSF/ANSI 173.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>We will seek to enroll 50 healthy control participants. We will attempt to enroll one control subject from each enrolled primary participant's home, preferably a spouse or partner of similar age if possible. We plan to use this data to compare the microbiome of control participants to that of the ALS participants at baseline, week 4 and month 6. We will not conduct further follow-up or collect additional samples with the control subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Theracurmin HP</intervention_name>
    <description>The intervention is based on the twice daily dosage of Theracurmin 90 mg capsules used in a trial of patients with mild cognitive impairment</description>
    <arm_group_label>Open Label Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged at least 18 years.&#xD;
&#xD;
          -  Sporadic or familial ALS diagnosed as possible, laboratory-supported probable,&#xD;
             probable, or definite as defined by revised El Escorial criteria.&#xD;
&#xD;
          -  Patient is able to understand and express informed consent (in the opinion of the site&#xD;
             investigator).&#xD;
&#xD;
          -  Patient has access to the Internet on a desktop computer, laptop, or tablet and has a&#xD;
             working email address.&#xD;
&#xD;
          -  Patient or caregiver is willing and able to use a computer and enter data on a secure&#xD;
             website.&#xD;
&#xD;
          -  Patient is able to read and write English.&#xD;
&#xD;
          -  Patient is expected to survive for the duration of the trial.&#xD;
&#xD;
          -  Women must not be pregnant (will have evidence of a negative pregnancy test obtained&#xD;
             by local physician within past 7 days or be post-menopausal)&#xD;
&#xD;
          -  Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile,&#xD;
             or using adequate birth control methods) for the duration of the study and three&#xD;
             months after study completion. Adequate contraception includes: abstinence, hormonal&#xD;
             contraception (oral contraception, implanted contraception, injected contraception or&#xD;
             other hormonal contraception, for example patch or contraceptive ring), intrauterine&#xD;
             device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide,&#xD;
             or another adequate method.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient is taking other experimental treatments for ALS (those that are part of an&#xD;
             active research study).&#xD;
&#xD;
          -  Prior side effects from curcumin or turmeric containing products&#xD;
&#xD;
          -  Patient has a medical or psychiatric illness that could in the investigator's opinion&#xD;
             interfere with the patient's ability to participate in this study.&#xD;
&#xD;
          -  Pregnant women or women currently breastfeeding.&#xD;
&#xD;
          -  Life expectancy shorter than the duration of the trial.&#xD;
&#xD;
          -  Taking an antiplatelet agent or anticoagulant (due to the theoretically increased risk&#xD;
             of bleeding from curcumin products).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Bedlack, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Richard Bedlack, M.D., Ph.D.</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 29, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04499963
org study id: pro00103700
nct id: NCT04499963
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial
      utilizing a historical control group.
This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial
      utilizing a historical control group. Following informed consent and screening, participants
      with ALS will take Theracurmin 1 capsule (90mg) twice daily for 6-months. Treatment with the
      Theracurmin and all study outcome measures and labs are being performed exclusively for
      research purposes. Collected data includes saliva and stool microbiome sampling, adverse
      events, concomitant medications, weight and height, Theracurmin treatment evaluations, and
      Thrive Questionnaires. Participants will be asked to register on the website Patientslikeme.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This will be a 6-month, widely inclusive, largely remote/virtual, single-center, open-label pilot trial utilizing a historical control group.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in ALSFRS-R score
time frame: Starting at week 4 and then once every 30 days for 6 months
description: The ALSFRS-R (ALS Functional Rating Scale-Revised) will be determined at all video/telephone visits. ALSFRS-R is a quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.
measure: ALS Reversals
time frame: month 6
description: To look for an increase in the frequency of ALS reversals, we will count the number of participants who have an ALSFRS-R score that improves by 4 points or more over 6 months. The observed frequency of spontaneous ALS reversals defined in this way is 2-5% (30). We will look for an increase in this frequency to at least 10% (1 in 10).
measure: Saliva Microbiome Sequencing change
time frame: Enrollment, week 4 and month 6 visits
description: The microbiome of study participants will be analyzed in saliva samples at enrollment, week 4 and month 6 visits. We will compare the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls.Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression.
measure: Number of adverse events as measured by patient reporting
time frame: Study duration, up to 6 months
description: Adverse and serious adverse events will be recorded throughout the study. The PI will determine whether these are related to treatment. Patients will also measure and record their side effects at Month 0-6 Internet Visits on their PLM profile.
measure: Enrollment Rate
time frame: one month
description: Enrollment rate will be calculated as the number of participants enrolled per month.
measure: Retention
time frame: month 6
description: Retention will be assessed by looking at the dropout rate at 6 months (the percentage of surviving enrolled patients who complete the Month 6 Visit).
measure: Stool Microbiome Sequencing change
time frame: Enrollment, week 4 and month 6 visits
description: The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Metagenomic analysis of deidentified selected fecal sample will be done on patients that positively respond to Theracurmin to achieve strain level identification of microbes positively and negatively associated with improved outcomes. The selected anaerobes that have been linked to ALS severity will be cultured for further genetic sand phenotypic characterization.
arm group label: Open Label Arm
arm group type: Experimental
description: The intervention is twice daily dosage of Theracurmin 90 mg capsules. This same dose was used in a successful trial of patients with mild cognitive impairment. Theracurmin HP capsules containing 90 mg curcumin each that will be taken as one capsule twice daily for 6 months. Each capsule contains 300 mg Theracurmin enhanced bioavailable water-dispersible turmeric rhizome complex providing 30% curcumin (90 mg). The content of Theracurmin HP has been independently certified by NSF International under NSF/ANSI 173.
arm group label: Healthy Control Arm
arm group type: No Intervention
description: We will seek to enroll 50 healthy control participants. We will attempt to enroll one control subject from each enrolled primary participant's home, preferably a spouse or partner of similar age if possible. We plan to use this data to compare the microbiome of control participants to that of the ALS participants at baseline, week 4 and month 6. We will not conduct further follow-up or collect additional samples with the control subjects.
intervention type: Drug
intervention name: Theracurmin HP
description: The intervention is based on the twice daily dosage of Theracurmin 90 mg capsules used in a trial of patients with mild cognitive impairment
arm group label: Open Label Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Richard Bedlack, MD, PhD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Richard Bedlack, M.D., Ph.D.
investigator title: Professor of Neurology
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
sharing ipd: No
submitted: August 29, 2023