Tocotrienols in Parkinson's Disease (PD)

Sponsor

National Neuroscience Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04491383

Collaborator

Hovid Berhad (Industry)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Neuro-Degenerative Disease Parkinson Disease	Drug: Tocovid Suprabio (HOV-12020) Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Experimental (Tocovid Suprabio (HOV-12020)) vs Control (Placebo)Experimental (Tocovid Suprabio (HOV-12020)) vs Control (Placebo)

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

This is a double-blind clinical trial.

Primary Purpose:

Treatment

Official Title:

Tocotrienols in Parkinson's Disease (PD): A Pilot, Randomised, Placebo-controlled Trial

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tocovid Suprabio (HOV-12020) 200mg, twice 1 day, 12 months	Drug: Tocovid Suprabio (HOV-12020) Dietary supplement: Tocotrienol (HOV-12020) Palm oil-derived vitamin E, tocotrienol
Placebo Comparator: Placebo 200mg, twice 1 day, 12 months	Other: Placebo Dietary supplement: Placebo. Placebo.

Arm

Intervention/Treatment

Experimental: Tocovid Suprabio (HOV-12020)

200mg, twice 1 day, 12 months

Drug: Tocovid Suprabio (HOV-12020)

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

Placebo Comparator: Placebo

200mg, twice 1 day, 12 months

Other: Placebo

Dietary supplement: Placebo. Placebo.

Outcome Measures

Primary Outcome Measures

Mean change from Baseline to Week 104 in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Score [104 weeks]
Score range is 0 to 199, with severity increasing with higher scores.

Secondary Outcome Measures

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]
Severity of disease increases with higher score.
Mean change from Baseline to Week 104 in quality of life, as measured by the Parkinson's Disease Questionnaire (PDQ-39) [104 weeks]
Score range is 0 to 100. A lower score will indicate a better quality of life.
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]
Severity of disease increases with higher score.
Mean change in levels of blood-based biomarkers (including total antioxidant status TAS, oxidative stress biomarkers and αsynuclein). [104 weeks]
Between treatment difference of type and incidence of Adverse Events (AEs) and Serious AEs (SAEs) [104 weeks]
Mean score change from Baseline to Week 104 in the MDS-UPDRS Part II scale [104 weeks]
Severity of disease increases with higher score.
Mean score change from Baseline to Week 104 in the Schwab and England Activities of Daily Living (SE-ADL) scale. [104 weeks]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 up to 14 days before baseline visit, and throughout the clinical study, unless prescribed by their physician for medical reasons.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Neuroscience Institute	Singapore		Singapore
2	Singapore General Hospital	Singapore		Singapore

Sponsors and Collaborators

National Neuroscience Institute
Hovid Berhad

Investigators

Principal Investigator: Eng King Tan, National Neuroscience Institute Singapore
Principal Investigator: Adeline Su-Lyn Ng, National Neuroscience Institute Singapore