Tocotrienols in Parkinson's Disease (PD)

NCT04491383 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: T3-PD-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Neuro-Degenerative Disease; Parkinson Disease

Keywords

Parkinson Disease; Vitamin E; Neurodegenerative Disease; Neurology

Outcome Measures

Primary Outcomes (1)

• Mean change from Baseline to Week 104 in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Score

  Score range is 0 to 199, with severity increasing with higher scores.

  104 weeks

Secondary Outcomes (8)

• Mean change from baseline to week 104 in disease severity

  104 weeks

• 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

  104 weeks

• Mean change from Baseline to Week 104 in quality of life, as measured by the Parkinson's Disease Questionnaire (PDQ-39)

  104 weeks

• 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.

  104 weeks

• Mean change in levels of blood-based biomarkers (including total antioxidant status TAS, oxidative stress biomarkers and αsynuclein).

  104 weeks

Study Arms (2)

Tocovid Suprabio (HOV-12020)

EXPERIMENTAL

200mg, twice 1 day, 12 months

Drug: Tocovid Suprabio (HOV-12020)

Placebo

PLACEBO COMPARATOR

200mg, twice 1 day, 12 months

Other: Placebo

Interventions

Tocovid Suprabio (HOV-12020) DRUG

Dietary supplement: Tocotrienol (HOV-12020) Palm oil-derived vitamin E, tocotrienol

Tocovid Suprabio (HOV-12020)

Placebo OTHER

Dietary supplement: Placebo. Placebo.

Placebo

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged between 40 - 90 years (inclusive).
• Able to provide written informed consent and able to comply with study protocol.
• Idiopathic PD of more than 1 years duration from diagnosis. The diagnosis must be confirmed by presence of bradykinesia and at least 1 other cardinal sign (resting tremor, rigidity), without any other known or suspected cause of parkinsonism.
• Hoehn \& Yahr =\> 2 with treatment.
• Patients on PD medication(s) e.g. levodopa, dopamine agonists, amantadine and/or Monoamine oxidase (MAO)-B inhibitors, must be on stable dose, for at least 30 days prior to screening. Medication and dose adjustments are allowed but must be documented.
• Patients on anti-depressant or anxiolytic medication must be on stable dose for at least 90 days prior to screening.
• The patient is willing to abstain from Vitamin E supplements (tocopherols and tocotrienols) and other dietary supplements which contain Vitamin E (tocopherols and tocotrienols) up to 14 days before baseline visit, and throughout the clinical study, unless prescribed by their physician for medical reasons.

You may not qualify if:

• Any other neurodegenerative disorder, such as Alzheimer's disease, Huntington's disease, or Creutzfeldt - Jakob disease.
• Current, clinically-significant hematological, cardiac, pulmonary, metabolic, neurologic or psychiatric disorders, uncontrolled seizures, untreated hypertension, disorders increasing risk of bleeding (Hemophilia), or any other significant active medical condition which, in the Investigator's opinion, would impact participation in this study.
• History of psychotic symptoms requiring treatment with a neuroleptic medication within the past 12 months.
• History of surgical or invasive intervention for PD (pallidotomy, thalamotomy, deep brain stimulation, etc.)
• Medical history indicating drug-induced parkinsonism (e.g., metoclopramide, flunarizine), metabolic identified neurogenetic disorders (e.g., Wilson's disease), encephalitis, or other atypical Parkinsonian syndromes (e.g., progressive supranuclear palsy, multiple system atrophy).
• History of myocardial infarction within 3 months prior to Screening, or current active angina pectoris, or symptomatic heart failure.
• Known liver disease or liver enzymes (AST, ALT) more than 5 times upper limit normal within 1 month of screening and enrolment.
• eGFR \<60 within 1 month of screening and enrolment.
• Current participation in another investigational interventional study.

Sponsors & Collaborators

• National Neuroscience Institute: lead

Study Sites (2)

National Neuroscience Institute

Singapore, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Related Publications (16)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 RESULT

• 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 RESULT

MeSH Terms

Conditions

Parkinson Disease; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies

Study Officials

• Eng King Tan

  National Neuroscience Institute Singapore

  PRINCIPAL INVESTIGATOR

• Adeline Su-Lyn Ng

  National Neuroscience Institute Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental (Tocovid Suprabio (HOV-12020)) vs Control (Placebo)

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 29, 2020
• Study Start: April 1, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)