<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/NCT04428983</url>
  </required_header>
  <id_info>
    <org_study_id>HELPD V4 20191120</org_study_id>
    <nct_id>NCT04428983</nct_id>
  </id_info>
  <brief_title>The Effect of Hericium Erinaceus Mycelium in Non-motor Symptoms of Parkinson's Disease</brief_title>
  <official_title>The Effect of Hericium Erinaceus Mycelium in Non-motor Symptoms of Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cheng-Kung University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cheng-Kung University Hospital</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>
      Parkinson disease (PD) is considered a multisystemic neurodegenerative disorder, together&#xD;
      with the classic motor disability, and a number of non-motor symptoms (NMS).NMS have a&#xD;
      significant negative relation with patients' quality of life. In general, both medicinal and&#xD;
      nonmedicinal therapies are often advised for PD patients with NMS, but robust evidences for&#xD;
      underpinning the clinical effects are limited. Recently, the search for small preventative&#xD;
      neurotrophic compounds that are responsible for the maintenance, survival of neurons has&#xD;
      attracted much attention. Erinacine A, which is extracted from Hericium erinaceus is the one&#xD;
      showed prominent beneficial effects in the central nervous system. It can increase NGF and&#xD;
      catecholamine content in the locus coeruleus and hippocampus of rats. This markedly increases&#xD;
      neuronal survival in different brain areas and substantially improve behavioral outcomes in&#xD;
      various animal models. In a MPTP-induced Parkinsonism model, treatment with Hericium&#xD;
      erinaceus mycelium reduced the loss of dopaminergic cell, eliminated neuronal apoptosis and&#xD;
      reversed MPTP-associated motor deficits. Thus, this project intends to hold a randomized,&#xD;
      controlled trial to assess the effect of Hericium erinaceus mycelium, which is enriched of&#xD;
      Erinacine A, in NMS of PD. This project will enroll 80 patients with PD. Subjects will be&#xD;
      randomly allocated into study or placebo group. Subjects will take Hericium erinaceus&#xD;
      mycelium for 2 years (one capsule per meal per day) and their treatments for PD will not be&#xD;
      altered.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Inclusion criteria:&#xD;
&#xD;
        1. PD patients aged 50-79 years diagnosed by neurologist (should exclude vascular&#xD;
           parkinsonism, secondary parkinsonism( including toxin, drug, heavy metal, CO&#xD;
           intoxication), normal pressure hydrocephalus, multiple system atrophy, progressive&#xD;
           supranuclear palsy, cortical basal degeneration, dementia with Lewy Body, hereditary&#xD;
           parkinson's disease with genetic mutation, Huntington's disease, Wilson disease, spinal&#xD;
           cerebellar ataxia with extrapyramidal syndrome, essential tremor, dystonia)&#xD;
&#xD;
        2. PD at Hoehn and Yahr stage 2-2.5&#xD;
&#xD;
        3. without cognitive decline&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        1. with diabetes mellitus (DM)&#xD;
&#xD;
        2. with nephropathy (GFR &lt; 30ml/min)&#xD;
&#xD;
        3. with significant neurological deficits caused by vascular insults&#xD;
&#xD;
      Measurement parameters:&#xD;
&#xD;
        1. At recruitment: blood sugar, AST, ALT, BUN, Crea, Ca, Na, K and peripheral blood cell&#xD;
           (for the expression levels of KATP)&#xD;
&#xD;
        2. every 6 months: motor symptoms: UPDRS, evaluate with UDYSRS if presence with dyskinesia&#xD;
           Non motor symptoms: self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D,&#xD;
           BPRS&#xD;
&#xD;
        3. every 1 year: CASI, tilting table, AST, ALT, BUN, crea, Na, K, Ca&#xD;
&#xD;
      Protocol:&#xD;
&#xD;
      0 month (initial baseline):&#xD;
&#xD;
        1. blood sugar, AST, ALT, BUN, Crea, Ca, Na, K and peripheral blood cell&#xD;
&#xD;
        2. Tilting table test (autonomic function)&#xD;
&#xD;
        3. CASI cognitive test&#xD;
&#xD;
        4. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:&#xD;
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS&#xD;
&#xD;
        5. stool microbiota&#xD;
&#xD;
      6 months: UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms:&#xD;
      self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS&#xD;
&#xD;
      12 months:&#xD;
&#xD;
        1. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:&#xD;
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS&#xD;
&#xD;
        2. CASI cognitive test, tilting table, AST, ALT, BUN, crea, Na, K, Ca&#xD;
&#xD;
      18 months: UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms:&#xD;
      self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS&#xD;
&#xD;
      24 months:&#xD;
&#xD;
        1. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:&#xD;
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS&#xD;
&#xD;
        2. CASI cognitive test, tilting table, AST, ALT, BUN, crea, Na, K, Ca&#xD;
&#xD;
        3. stool microbiota&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 3, 2020</start_date>
  <completion_date type="Anticipated">March 20, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 20, 2022</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>baseline</measure>
    <time_frame>0 month</time_frame>
    <description>Unified Parkinson's Disease Rating Scale (MDS-UPDRS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1st</measure>
    <time_frame>6 momths</time_frame>
    <description>Unified Parkinson's Disease Rating Scale (MDS-UPDRS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2nd</measure>
    <time_frame>12 months</time_frame>
    <description>Unified Parkinson's Disease Rating Scale (MDS-UPDRS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>3rd</measure>
    <time_frame>18 months</time_frame>
    <description>UPDRS</description>
  </primary_outcome>
  <primary_outcome>
    <measure>final</measure>
    <time_frame>24 months</time_frame>
    <description>Unified Parkinson's Disease Rating Scale (MDS-UPDRS)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Hericium erinaceus mycelium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hericium erinaceus capsules 1 table tid orally per day for 24 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo capsules 1 table tid orally per day for 24 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Hericium erinaceus mycelium</intervention_name>
    <description>Hericium erinaceus capsules 3 tables per day for 24 months</description>
    <arm_group_label>Hericium erinaceus mycelium</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  idiopathic PD patients, aged 50-79 years&#xD;
&#xD;
          -  modified Hoehn &amp; Yahr stage 2-2.5&#xD;
&#xD;
          -  Without subjective and objective cognitive decline (objective cognitive decline will&#xD;
             be determined by CASI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  With diabetes&#xD;
&#xD;
          -  With end stage renal disease under hemodialysis&#xD;
&#xD;
          -  With significant vascular insults that resulted in significant neurological deficits&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Li-Ya Lee</last_name>
    <role>Study Director</role>
    <affiliation>Bioengineering Center, Grape King Bio</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Li-Ya Lee</last_name>
    <phone>+886-3-4572525</phone>
    <phone_ext>2995</phone_ext>
    <email>ly.lee@grapeking.com.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuan-Ting Sun, MD PhD</last_name>
      <phone>+886-6-2353535</phone>
      <email>ytsun@mail.ncku.edu.tw</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>November 20, 2019</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cheng-Kung University Hospital</investigator_affiliation>
    <investigator_full_name>Yuan-Ting Sun</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <keyword>Parkinson Disease, non-motor symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04428983
org study id: HELPD V4 20191120
nct id: NCT04428983
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Parkinson disease (PD) is considered a multisystemic neurodegenerative disorder, together
      with the classic motor disability, and a number of non-motor symptoms (NMS).NMS have a
      significant negative relation with patients' quality of life. In general, both medicinal and
      nonmedicinal therapies are often advised for PD patients with NMS, but robust evidences for
      underpinning the clinical effects are limited. Recently, the search for small preventative
      neurotrophic compounds that are responsible for the maintenance, survival of neurons has
      attracted much attention. Erinacine A, which is extracted from Hericium erinaceus is the one
      showed prominent beneficial effects in the central nervous system. It can increase NGF and
      catecholamine content in the locus coeruleus and hippocampus of rats. This markedly increases
      neuronal survival in different brain areas and substantially improve behavioral outcomes in
      various animal models. In a MPTP-induced Parkinsonism model, treatment with Hericium
      erinaceus mycelium reduced the loss of dopaminergic cell, eliminated neuronal apoptosis and
      reversed MPTP-associated motor deficits. Thus, this project intends to hold a randomized,
      controlled trial to assess the effect of Hericium erinaceus mycelium, which is enriched of
      Erinacine A, in NMS of PD. This project will enroll 80 patients with PD. Subjects will be
      randomly allocated into study or placebo group. Subjects will take Hericium erinaceus
      mycelium for 2 years (one capsule per meal per day) and their treatments for PD will not be
      altered.
Inclusion criteria:

        1. PD patients aged 50-79 years diagnosed by neurologist (should exclude vascular
           parkinsonism, secondary parkinsonism( including toxin, drug, heavy metal, CO
           intoxication), normal pressure hydrocephalus, multiple system atrophy, progressive
           supranuclear palsy, cortical basal degeneration, dementia with Lewy Body, hereditary
           parkinson's disease with genetic mutation, Huntington's disease, Wilson disease, spinal
           cerebellar ataxia with extrapyramidal syndrome, essential tremor, dystonia)

        2. PD at Hoehn and Yahr stage 2-2.5

        3. without cognitive decline

      Exclusion criteria:

        1. with diabetes mellitus (DM)

        2. with nephropathy (GFR < 30ml/min)

        3. with significant neurological deficits caused by vascular insults

      Measurement parameters:

        1. At recruitment: blood sugar, AST, ALT, BUN, Crea, Ca, Na, K and peripheral blood cell
           (for the expression levels of KATP)

        2. every 6 months: motor symptoms: UPDRS, evaluate with UDYSRS if presence with dyskinesia
           Non motor symptoms: self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D,
           BPRS

        3. every 1 year: CASI, tilting table, AST, ALT, BUN, crea, Na, K, Ca

      Protocol:

      0 month (initial baseline):

        1. blood sugar, AST, ALT, BUN, Crea, Ca, Na, K and peripheral blood cell

        2. Tilting table test (autonomic function)

        3. CASI cognitive test

        4. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS

        5. stool microbiota

      6 months: UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms:
      self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS

      12 months:

        1. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS

        2. CASI cognitive test, tilting table, AST, ALT, BUN, crea, Na, K, Ca

      18 months: UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms:
      self-report: PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS

      24 months:

        1. UPDRS, evaluate with UDYSRS if presence with dyskinesia Non motor symptoms: self-report:
           PDQ39, QUIP, PDSS Rated by neurologist: NMSS, HAM-D, BPRS

        2. CASI cognitive test, tilting table, AST, ALT, BUN, crea, Na, K, Ca

        3. stool microbiota
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: baseline
time frame: 0 month
description: Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
measure: 1st
time frame: 6 momths
description: Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
measure: 2nd
time frame: 12 months
description: Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
measure: 3rd
time frame: 18 months
description: UPDRS
measure: final
time frame: 24 months
description: Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
arm group label: Hericium erinaceus mycelium
arm group type: Experimental
description: Hericium erinaceus capsules 1 table tid orally per day for 24 months
arm group label: placebo
arm group type: Placebo Comparator
description: placebo capsules 1 table tid orally per day for 24 months
intervention type: Dietary Supplement
intervention name: Hericium erinaceus mycelium
description: Hericium erinaceus capsules 3 tables per day for 24 months
arm group label: Hericium erinaceus mycelium
arm group label: placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 79 Years
healthy volunteers: No
last name: Li-Ya Lee
role: Study Director
affiliation: Bioengineering Center, Grape King Bio
last name: Li-Ya Lee
phone: +886-3-4572525
phone ext: 2995
email: ly.lee@grapeking.com.tw
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Cheng-Kung University Hospital
investigator full name: Yuan-Ting Sun
investigator title: Doctor
mesh term: Parkinson Disease
sharing ipd: Undecided