The Efficacy and Safety of Vitamin E Mixed Tocotrienols In Patients With Amyotrophic Lateral Sclerosis (ALS)

• ClinicalTrials.gov Identifier: NCT04140136
• Recruitment Status: Recruiting
• First Posted: October 25, 2019
• Last Update Posted: October 25, 2019
• Sponsor: University of Malaya
• Information provided by (Responsible Party): Professor Nortina Shahrizaila, University of Malaya

Study Description

Brief Summary:

There is currently no effective treatment in ALS. Oxidative stress, probably interacting with other neurodegenerative processes, is hypothesized to play a leading role in pathogenesis. These include mechanisms that promote glutamate excitotoxicity, mitochondrial dysfunction and axonal dysfunction.

In a transgenic mouse model of fALS that develops a disease with a clinical phenotype similar to ALS, dietary vitamin E supplementation delayed disease onset and slowed progression, although it did not prolong survival. When used as an experimental therapy in human trials, vitamin E did not affect survival significantly, but possibly slowed ALS progression. Two large, prospective epidemiologic studies suggest that longterm use of vitamin E supplements could be inversely associated with risk of ALS or ALS death. In another study, higher baseline serum α-tocopherol was associated with lower subsequent risk of ALS. A modest, non-significant protective effect from supplementation was seen in subjects with baseline serum α-tocopherol levels below median levels. In the current study, we aim to investigate the effects of tocotrienols in patients with ALS, particularly in delaying disease progression as well as assessing its safety profile in this group of patients.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Dietary Supplement: Tocotrienols; Dietary Supplement: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of Vitamin E Mixed Tocotrienols In Patients With Amyotrophic Lateral Sclerosis (ALS) : A Pilot Exploratory Study
• Actual Study Start Date: June 17, 2019
• Estimated Primary Completion Date: April 1, 2020
• Estimated Study Completion Date: September 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment group; This is a pilot randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effects of 24-weeks tocotrienols (Tocovid Suprabio) supplementation in ALS patients.The investigational product is to be administered twice daily, at a dose of 400mg per day.	Dietary Supplement: Tocotrienols; Tocotrienols as a potent antioxidant to modulate oxidative stress and inflammatory response
Placebo Comparator: Placebo group; This is a pilot randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effects of 24-weeks tocotrienols (Tocovid Suprabio) supplementation in ALS patients. The placebo is similar in appearance but does not contain tocotrienols and consist of palm oil.	Dietary Supplement: Placebo; The placebo is similar in appearance, but does not contain tocotrienols and consist of palm oil

Outcome Measures

Primary Outcome Measures :

1. Mean change of revised ALS Functional Rating Scale (ALSFRS-R) at baseline and 6 months between treatment group difference. [ Time Frame: 6 months ]
   Efficacy of oral mixed Tocotrienols in patients with ALS in delaying disease progression as assess based on the cumulative score of ALSFRS-R between treatment group difference at specific time point.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events,haematological,renal and liver profile monitored at every visit [ Time Frame: 6 months ]
   Safety of oral mixed Tocotrienols in ALS patients

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients who have a decrease of 1 to 4 points on the ALSFRS-R score during the 12-weeks observation period prior to screening and enrollment
• Patients of less than 2 years after the diagnosis of ALS.
• Patients without respiratory symptoms (orthopnea, dyspnea)
• Capable of giving signed informed consent

Exclusion Criteria:

• Patients who have developed respiratory failure necessitating ventilation
• Patients who have developed unsafe swallowing necessitating enteral feeding tube insertion
• Patients with other neurodegenerative disease such as Parkinson's disease and significant mental health illness
• Patients with certain concomitant diseases which may affect the assessment of safety/efficacy i.e. malignancy within the last 5 years, congestive heart disease, liver disease, kidney failure, bleeding disorders and other autoimmune diseases etc.
• Pregnant, lactating, and probably pregnant patients.
• Patients taking vitamin E tocopherol or tocotrienols supplements within 1 month from screening and randomisation.
• Patients who have participated in other trials within 12 weeks before consent, or who are participating in other clinical trials at present.
• Women of child bearing potential or nursing mother, unless they are willing to practice effective contraceptive measures.

Contacts and Locations

Contacts

Contact: Piek Lian Wang; +603-79492622; wangpl@ummc.edu.my

Locations

Malaysia

Clinical Investigation Centre (CIC); Recruiting

Kuala Lumpur, Malaysia, 59100

Contact: Piek Lian Wang +603-79492622 wangpl@ummc.edu.my

Principal Investigator: Nortina Shahrizaila

Sponsors and Collaborators

University of Malaya

More Information

• Responsible Party: Professor Nortina Shahrizaila, Professor, University of Malaya
• ClinicalTrials.gov Identifier: NCT04140136 History of Changes
• Other Study ID Numbers: 2018613-6392
• First Posted: October 25, 2019
• Last Update Posted: October 25, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Professor Nortina Shahrizaila, University of Malaya:

ALS

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Vitamin E; Tocopherols; Tocotrienols; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents