<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/NCT04491383</url>
  </required_header>
  <id_info>
    <org_study_id>T3-PD-01</org_study_id>
    <nct_id>NCT04491383</nct_id>
  </id_info>
  <brief_title>Tocotrienols in Parkinson's Disease (PD)</brief_title>
  <official_title>Tocotrienols in Parkinson's Disease (PD): A Pilot, Randomised, Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Neuroscience Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hovid Berhad</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Neuroscience Institute</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      A study using Parkinson's disease animal model, transgenic fruit flies, demonstrated the&#xD;
      potential of using tocotrienols (HOV-12020) as a therapeutic agent for delaying Parkinsonian&#xD;
      motor dysfunctions. The proposed study aims to enrol 100 PD patients in a randomized&#xD;
      placebo-controlled trial to investigate the effects of tocotrienols (HOV-12020) in motor and&#xD;
      non-motor outcomes. Patients will be given oral tocotrienols (400mg/day) or placebo for 104&#xD;
      weeks. They will be assessed using the standard assessments scales in PD at baseline, Week 52&#xD;
      and Week 104. Neuropsychological evaluation will also be completed at these intervals to&#xD;
      monitor progression of cognitive impairment (if any). Additional PD staging using MDSUPDRS&#xD;
      (Part III), Hoehn &amp; Yahr (H&amp;Y) will be conducted at Week 26 and week 78. Blood samples will&#xD;
      be collected to evaluate PD biomarkers and for safety monitoring (liver function, renal&#xD;
      function and hematology).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 2</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>Experimental (Tocovid Suprabio (HOV-12020)) vs Control (Placebo)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This is a double-blind clinical trial.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change from Baseline to Week 104 in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Score</measure>
    <time_frame>104 weeks</time_frame>
    <description>Score range is 0 to 199, with severity increasing with higher scores.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline to week 104 in disease severity</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline to week 104 in individual cognitive domain z scores on comprehensive neuropsychological testing mean score change from baseline to week 104 in the MDS-UPDRS score for total score</measure>
    <time_frame>104 weeks</time_frame>
    <description>Severity of disease increases with higher score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from Baseline to Week 104 in quality of life, as measured by the Parkinson's Disease Questionnaire (PDQ-39)</measure>
    <time_frame>104 weeks</time_frame>
    <description>Score range is 0 to 100. A lower score will indicate a better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference proportion of patients with change from Baseline to Week 104, above or equal to the minimal clinically important difference (MCID) of the motor score, as measured by Part II and III subscales of MDS-UPDRS.</measure>
    <time_frame>104 weeks</time_frame>
    <description>Severity of disease increases with higher score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in levels of blood-based biomarkers (including total antioxidant status TAS, oxidative stress biomarkers and αsynuclein).</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Between treatment difference of type and incidence of Adverse Events (AEs) and Serious AEs (SAEs)</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean score change from Baseline to Week 104 in the MDS-UPDRS Part II scale</measure>
    <time_frame>104 weeks</time_frame>
    <description>Severity of disease increases with higher score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean score change from Baseline to Week 104 in the Schwab and England Activities of Daily Living (SE-ADL) scale.</measure>
    <time_frame>104 weeks</time_frame>
    <description>The scale uses percentages to assess the difficulties completing daily activities/chores, from 0% to 100%. A higher percentage will indicate a better outcome (i.e. more independence for an individual).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Neuro-Degenerative Disease</condition>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Tocovid Suprabio (HOV-12020)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200mg, twice 1 day, 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>200mg, twice 1 day, 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocovid Suprabio (HOV-12020)</intervention_name>
    <description>Dietary supplement: Tocotrienol (HOV-12020) Palm oil-derived vitamin E, tocotrienol</description>
    <arm_group_label>Tocovid Suprabio (HOV-12020)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Dietary supplement: Placebo. Placebo.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women aged between 40 - 90 years (inclusive).&#xD;
&#xD;
          -  Able to provide written informed consent and able to comply with study protocol.&#xD;
&#xD;
          -  Idiopathic PD of more than 1 years duration from diagnosis. The diagnosis must be&#xD;
             confirmed by presence of bradykinesia and at least 1 other cardinal sign (resting&#xD;
             tremor, rigidity), without any other known or suspected cause of parkinsonism.&#xD;
&#xD;
          -  Hoehn &amp; Yahr =&gt; 2 with treatment.&#xD;
&#xD;
          -  Patients on PD medication(s) e.g. levodopa, dopamine agonists, amantadine and/or&#xD;
             Monoamine oxidase (MAO)-B inhibitors, must be on stable dose, for at least 30 days&#xD;
             prior to screening. Medication and dose adjustments are allowed but must be&#xD;
             documented.&#xD;
&#xD;
          -  Patients on anti-depressant or anxiolytic medication must be on stable dose for at&#xD;
             least 90 days prior to screening.&#xD;
&#xD;
          -  The patient is willing to abstain from Vitamin E supplements (tocopherols and&#xD;
             tocotrienols) and other dietary supplements which contain Vitamin E (tocopherols and&#xD;
             tocotrienols) up to 14 days before baseline visit, and throughout the clinical study,&#xD;
             unless prescribed by their physician for medical reasons.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any other neurodegenerative disorder, such as Alzheimer's disease, Huntington's&#xD;
             disease, or Creutzfeldt - Jakob disease.&#xD;
&#xD;
          -  Current, clinically-significant hematological, cardiac, pulmonary, metabolic,&#xD;
             neurologic or psychiatric disorders, uncontrolled seizures, untreated hypertension,&#xD;
             disorders increasing risk of bleeding (Hemophilia), or any other significant active&#xD;
             medical condition which, in the Investigator's opinion, would impact participation in&#xD;
             this study.&#xD;
&#xD;
          -  History of psychotic symptoms requiring treatment with a neuroleptic medication within&#xD;
             the past 12 months.&#xD;
&#xD;
          -  History of surgical or invasive intervention for PD (pallidotomy, thalamotomy, deep&#xD;
             brain stimulation, etc.)&#xD;
&#xD;
          -  Medical history indicating drug-induced parkinsonism (e.g., metoclopramide,&#xD;
             flunarizine), metabolic identified neurogenetic disorders (e.g., Wilson's disease),&#xD;
             encephalitis, or other atypical Parkinsonian syndromes (e.g., progressive supranuclear&#xD;
             palsy, multiple system atrophy).&#xD;
&#xD;
          -  History of myocardial infarction within 3 months prior to Screening, or current active&#xD;
             angina pectoris, or symptomatic heart failure.&#xD;
&#xD;
          -  Known liver disease or liver enzymes (AST, ALT) more than 5 times upper limit normal&#xD;
             within 1 month of screening and enrolment.&#xD;
&#xD;
          -  eGFR &lt;60 within 1 month of screening and enrolment.&#xD;
&#xD;
          -  Current participation in another investigational interventional study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eng King Tan</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Neuroscience Institute Singapore</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adeline Su-Lyn Ng</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Neuroscience Institute Singapore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elaine Ang</last_name>
    <phone>(65) 65762660</phone>
    <email>elaine.ang.s.l@sgh.com.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Neuroscience Institute</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elaine Ang</last_name>
    </contact>
    <investigator>
      <last_name>Adeline Su Lyn Ng</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elaine Ang</last_name>
    </contact>
    <investigator>
      <last_name>Eng King Tan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76. doi: 10.1136/jnnp.2007.131045.</citation>
    <PMID>18344392</PMID>
  </reference>
  <reference>
    <citation>Gandhi S, Wood NW. Molecular pathogenesis of Parkinson's disease. Hum Mol Genet. 2005 Sep 15;14(18):2749-55. doi: 10.1093/hmg/ddi308. Epub 2005 Aug 26.</citation>
    <PMID>16126732</PMID>
  </reference>
  <reference>
    <citation>Khanna S, Rink C, Ghoorkhanian R, Gnyawali S, Heigel M, Wijesinghe DS, Chalfant CE, Chan YC, Banerjee J, Huang Y, Roy S, Sen CK. Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size. J Cereb Blood Flow Metab. 2013 Aug;33(8):1197-206. doi: 10.1038/jcbfm.2013.68. Epub 2013 May 1.</citation>
    <PMID>23632968</PMID>
  </reference>
  <reference>
    <citation>Rink C, Christoforidis G, Khanna S, Peterson L, Patel Y, Khanna S, Abduljalil A, Irfanoglu O, Machiraju R, Bergdall VK, Sen CK. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30. doi: 10.1038/jcbfm.2011.85. Epub 2011 Jun 15.</citation>
    <PMID>21673716</PMID>
  </reference>
  <reference>
    <citation>Silbert LC, Howieson DB, Dodge H, Kaye JA. Cognitive impairment risk: white matter hyperintensity progression matters. Neurology. 2009 Jul 14;73(2):120-5. doi: 10.1212/WNL.0b013e3181ad53fd.</citation>
    <PMID>19597134</PMID>
  </reference>
  <reference>
    <citation>Srikanth VK, Quinn SJ, Donnan GA, Saling MM, Thrift AG. Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based first-ever stroke cohort. Stroke. 2006 Oct;37(10):2479-83. doi: 10.1161/01.STR.0000239666.46828.d7. Epub 2006 Aug 31.</citation>
    <PMID>16946165</PMID>
  </reference>
  <reference>
    <citation>Sen CK, Rink C, Khanna S. Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease. J Am Coll Nutr. 2010 Jun;29(3 Suppl):314S-323S. doi: 10.1080/07315724.2010.10719846.</citation>
    <PMID>20823491</PMID>
  </reference>
  <reference>
    <citation>Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology. 2009 Sep;57(4):456-62. doi: 10.1016/j.neuropharm.2009.06.013. Epub 2009 Jun 23.</citation>
    <PMID>19555701</PMID>
  </reference>
  <reference>
    <citation>Khanna S, Roy S, Slivka A, Craft TK, Chaki S, Rink C, Notestine MA, DeVries AC, Parinandi NL, Sen CK. Neuroprotective properties of the natural vitamin E alpha-tocotrienol. Stroke. 2005 Oct;36(10):2258-64. doi: 10.1161/01.STR.0000181082.70763.22. Epub 2005 Sep 15.</citation>
    <PMID>16166580</PMID>
  </reference>
  <reference>
    <citation>Khanna S, Roy S, Ryu H, Bahadduri P, Swaan PW, Ratan RR, Sen CK. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem. 2003 Oct 31;278(44):43508-15. doi: 10.1074/jbc.M307075200. Epub 2003 Aug 13.</citation>
    <PMID>12917400</PMID>
  </reference>
  <reference>
    <citation>Sen CK, Khanna S, Roy S, Packer L. Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells. J Biol Chem. 2000 Apr 28;275(17):13049-55. doi: 10.1074/jbc.275.17.13049.</citation>
    <PMID>10777609</PMID>
  </reference>
  <reference>
    <citation>Khanna S, Parinandi NL, Kotha SR, Roy S, Rink C, Bibus D, Sen CK. Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection. J Neurochem. 2010 Mar;112(5):1249-60. doi: 10.1111/j.1471-4159.2009.06550.x. Epub 2009 Dec 17.</citation>
    <PMID>20028458</PMID>
  </reference>
  <reference>
    <citation>Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol. 2010 Dec 1;80(11):1613-31. doi: 10.1016/j.bcp.2010.07.043. Epub 2010 Aug 7.</citation>
    <PMID>20696139</PMID>
  </reference>
  <reference>
    <citation>Vitamin E in Neuroprotection Study (VENUS) Investigators; Hor CP, Fung WY, Ang HA, Lim SC, Kam LY, Sim SW, Lim LH, Choon WY, Wong JW, Ch'ng ASH, Beh KKM, Wee HC, Ong LM, Khan NAK, Sulaiman SAS, Shuaib IL, Bakar A, Yusof Y, Yusof YM, Abu Bakar F, Tang WS, Teh HL, Wahid NA, Saaidin S, Idris N, Yoon CK, Ong HN, Ganapathy JT, Loo CE, Samy MM, Zainal H, Dharan SCS, Ooi BY, Teoh PY, Tye YL, Yeoh CA, Low DW, Looi I, Yuen KH. Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial. JAMA Neurol. 2018 Apr 1;75(4):444-452. doi: 10.1001/jamaneurol.2017.4609.</citation>
    <PMID>29379943</PMID>
  </reference>
  <results_reference>
    <citation>Farooqui T, Farooqui AA. Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson's disease. Parkinsons Dis. 2011 Feb 15;2011:247467. doi: 10.4061/2011/247467.</citation>
    <PMID>21403820</PMID>
  </results_reference>
  <results_reference>
    <citation>Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014 May;45(5):1422-8. doi: 10.1161/STROKEAHA.113.004449. Epub 2014 Apr 3.</citation>
    <PMID>24699052</PMID>
  </results_reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>September 14, 2022</last_update_submitted>
  <last_update_submitted_qc>September 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson Disease</keyword>
  <keyword>Vitamin E</keyword>
  <keyword>Neurodegenerative Disease</keyword>
  <keyword>Neurology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Neurodegenerative Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tocovid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is not a plan to make IPD available.</ipd_description>
  </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/NCT04491383
org study id: T3-PD-01
nct id: NCT04491383
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A study using Parkinson's disease animal model, transgenic fruit flies, demonstrated the
      potential of using tocotrienols (HOV-12020) as a therapeutic agent for delaying Parkinsonian
      motor dysfunctions. The proposed study aims to enrol 100 PD patients in a randomized
      placebo-controlled trial to investigate the effects of tocotrienols (HOV-12020) in motor and
      non-motor outcomes. Patients will be given oral tocotrienols (400mg/day) or placebo for 104
      weeks. They will be assessed using the standard assessments scales in PD at baseline, Week 52
      and Week 104. Neuropsychological evaluation will also be completed at these intervals to
      monitor progression of cognitive impairment (if any). Additional PD staging using MDSUPDRS
      (Part III), Hoehn & Yahr (H&Y) will be conducted at Week 26 and week 78. Blood samples will
      be collected to evaluate PD biomarkers and for safety monitoring (liver function, renal
      function and hematology).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Experimental (Tocovid Suprabio (HOV-12020)) vs Control (Placebo)
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This is a double-blind clinical trial.
measure: Mean change from Baseline to Week 104 in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Score
time frame: 104 weeks
description: Score range is 0 to 199, with severity increasing with higher scores.
measure: Mean change from baseline to week 104 in disease severity
time frame: 104 weeks
measure: Mean change from baseline to week 104 in individual cognitive domain z scores on comprehensive neuropsychological testing mean score change from baseline to week 104 in the MDS-UPDRS score for total score
time frame: 104 weeks
description: Severity of disease increases with higher score.
measure: Mean change from Baseline to Week 104 in quality of life, as measured by the Parkinson's Disease Questionnaire (PDQ-39)
time frame: 104 weeks
description: Score range is 0 to 100. A lower score will indicate a better quality of life.
measure: Difference proportion of patients with change from Baseline to Week 104, above or equal to the minimal clinically important difference (MCID) of the motor score, as measured by Part II and III subscales of MDS-UPDRS.
time frame: 104 weeks
description: Severity of disease increases with higher score.
measure: Mean change in levels of blood-based biomarkers (including total antioxidant status TAS, oxidative stress biomarkers and αsynuclein).
time frame: 104 weeks
measure: Between treatment difference of type and incidence of Adverse Events (AEs) and Serious AEs (SAEs)
time frame: 104 weeks
measure: Mean score change from Baseline to Week 104 in the MDS-UPDRS Part II scale
time frame: 104 weeks
description: Severity of disease increases with higher score.
measure: Mean score change from Baseline to Week 104 in the Schwab and England Activities of Daily Living (SE-ADL) scale.
time frame: 104 weeks
description: The scale uses percentages to assess the difficulties completing daily activities/chores, from 0% to 100%. A higher percentage will indicate a better outcome (i.e. more independence for an individual).
arm group label: Tocovid Suprabio (HOV-12020)
arm group type: Experimental
description: 200mg, twice 1 day, 12 months
arm group label: Placebo
arm group type: Placebo Comparator
description: 200mg, twice 1 day, 12 months
intervention type: Drug
intervention name: Tocovid Suprabio (HOV-12020)
description: Dietary supplement: Tocotrienol (HOV-12020) Palm oil-derived vitamin E, tocotrienol
arm group label: Tocovid Suprabio (HOV-12020)
intervention type: Other
intervention name: Placebo
description: Dietary supplement: Placebo. Placebo.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 90 Years
healthy volunteers: No
last name: Eng King Tan
role: Principal Investigator
affiliation: National Neuroscience Institute Singapore
last name: Adeline Su-Lyn Ng
role: Principal Investigator
affiliation: National Neuroscience Institute Singapore
last name: Elaine Ang
phone: (65) 65762660
email: elaine.ang.s.l@sgh.com.sg
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Singapore
citation: Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76. doi: 10.1136/jnnp.2007.131045.
PMID: 18344392
citation: Gandhi S, Wood NW. Molecular pathogenesis of Parkinson's disease. Hum Mol Genet. 2005 Sep 15;14(18):2749-55. doi: 10.1093/hmg/ddi308. Epub 2005 Aug 26.
PMID: 16126732
citation: Khanna S, Rink C, Ghoorkhanian R, Gnyawali S, Heigel M, Wijesinghe DS, Chalfant CE, Chan YC, Banerjee J, Huang Y, Roy S, Sen CK. Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size. J Cereb Blood Flow Metab. 2013 Aug;33(8):1197-206. doi: 10.1038/jcbfm.2013.68. Epub 2013 May 1.
PMID: 23632968
citation: Rink C, Christoforidis G, Khanna S, Peterson L, Patel Y, Khanna S, Abduljalil A, Irfanoglu O, Machiraju R, Bergdall VK, Sen CK. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30. doi: 10.1038/jcbfm.2011.85. Epub 2011 Jun 15.
PMID: 21673716
citation: Silbert LC, Howieson DB, Dodge H, Kaye JA. Cognitive impairment risk: white matter hyperintensity progression matters. Neurology. 2009 Jul 14;73(2):120-5. doi: 10.1212/WNL.0b013e3181ad53fd.
PMID: 19597134
citation: Srikanth VK, Quinn SJ, Donnan GA, Saling MM, Thrift AG. Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based first-ever stroke cohort. Stroke. 2006 Oct;37(10):2479-83. doi: 10.1161/01.STR.0000239666.46828.d7. Epub 2006 Aug 31.
PMID: 16946165
citation: Sen CK, Rink C, Khanna S. Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease. J Am Coll Nutr. 2010 Jun;29(3 Suppl):314S-323S. doi: 10.1080/07315724.2010.10719846.
PMID: 20823491
citation: Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology. 2009 Sep;57(4):456-62. doi: 10.1016/j.neuropharm.2009.06.013. Epub 2009 Jun 23.
PMID: 19555701
citation: Khanna S, Roy S, Slivka A, Craft TK, Chaki S, Rink C, Notestine MA, DeVries AC, Parinandi NL, Sen CK. Neuroprotective properties of the natural vitamin E alpha-tocotrienol. Stroke. 2005 Oct;36(10):2258-64. doi: 10.1161/01.STR.0000181082.70763.22. Epub 2005 Sep 15.
PMID: 16166580
citation: Khanna S, Roy S, Ryu H, Bahadduri P, Swaan PW, Ratan RR, Sen CK. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem. 2003 Oct 31;278(44):43508-15. doi: 10.1074/jbc.M307075200. Epub 2003 Aug 13.
PMID: 12917400
citation: Sen CK, Khanna S, Roy S, Packer L. Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells. J Biol Chem. 2000 Apr 28;275(17):13049-55. doi: 10.1074/jbc.275.17.13049.
PMID: 10777609
citation: Khanna S, Parinandi NL, Kotha SR, Roy S, Rink C, Bibus D, Sen CK. Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection. J Neurochem. 2010 Mar;112(5):1249-60. doi: 10.1111/j.1471-4159.2009.06550.x. Epub 2009 Dec 17.
PMID: 20028458
citation: Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol. 2010 Dec 1;80(11):1613-31. doi: 10.1016/j.bcp.2010.07.043. Epub 2010 Aug 7.
PMID: 20696139
citation: Vitamin E in Neuroprotection Study (VENUS) Investigators; Hor CP, Fung WY, Ang HA, Lim SC, Kam LY, Sim SW, Lim LH, Choon WY, Wong JW, Ch'ng ASH, Beh KKM, Wee HC, Ong LM, Khan NAK, Sulaiman SAS, Shuaib IL, Bakar A, Yusof Y, Yusof YM, Abu Bakar F, Tang WS, Teh HL, Wahid NA, Saaidin S, Idris N, Yoon CK, Ong HN, Ganapathy JT, Loo CE, Samy MM, Zainal H, Dharan SCS, Ooi BY, Teoh PY, Tye YL, Yeoh CA, Low DW, Looi I, Yuen KH. Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial. JAMA Neurol. 2018 Apr 1;75(4):444-452. doi: 10.1001/jamaneurol.2017.4609.
PMID: 29379943
citation: Farooqui T, Farooqui AA. Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson's disease. Parkinsons Dis. 2011 Feb 15;2011:247467. doi: 10.4061/2011/247467.
PMID: 21403820
citation: Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014 May;45(5):1422-8. doi: 10.1161/STROKEAHA.113.004449. Epub 2014 Apr 3.
PMID: 24699052
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Neurodegenerative Diseases
mesh term: Tocovid
sharing ipd: No
ipd description: There is not a plan to make IPD available.