A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Vitamin E δ-Tocotrienol Following Multiple Dose Administration in Healthy Subjects

Shivakumar Vignesh, M.D.H. Lee Moffitt Cancer Center and Research Institute

Ongoing

Study Type: Phase 1, Interventional
Study Design: Open Label, Safety Efficacy Study
Subjects: Healthy volunteers
Intervention: Vitamin E δ-tocotrienol (Davos Life Science Pte Ltd)

Primary Outcome:

  • Safety and tolerability of Vitamin E δ-Tocotrienol
  • Maximum administered dose (MAD) or maximum tolerated dose (MTD) of Vitamin E δ-Tocotrienol

Secondary Outcome:

  • Effects of dose on the plasma pharmacokinetic (PK) of Vitamin E δ-Tocotrienol
  • Biomolecular markers not limited to Erk, p-Erk, AKT, p-AKT, p27, Ki-67, and exportin.

Methodology: Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days. Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The first cohort will be dosed with δ-tocotrienol at 100 mg twice daily for 14 consecutive days. A minimum of 3 subjects is planned for each dosing cohort with Vitamin E δ-Tocotrienol dose escalation dependent on safety and available PK data from prior cohorts. At the MTD or MAD, 20 subjects will be enrolled.

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Phase 1a: A Randomized, 2-period Cross-over Study to Compare the Bioavailability of Gamma-Delta Tocotrienol (GDT) With That of Tocotrienol Rich Fraction (TRF) in Twelve Healthy Subjects

Nur Aishah Mohd Taib University Malaya Medical Centre

Ongoing

Objective: To compare the rate and extent of absorption and pharmacokinetics of the newly formulated Gamma-Delta formulation with TRF in healthy volunteers

Study Type: Interventional

Study Design: Randomized, double-blind, cross-over

Subjects: Healthy volunteers

Intervention: Gamma-delta tocotrienol, tocotrienol-rich fraction (Davos Life Science Pte Ltd)

Primary Outcome: Peak Plasma Concentration (Cmax) of drug [Time Frame: 0 to 24 hours after dosing ]

Methodology: Twelve healthy subjects will be admitted to a clinical study ward on the Day 0. Physical check up and the health status will be confirmed during check in. After fasting for a minimum of 10 hours overnight, each subject will be administered a single dose of TRF or Gamma-Delta after taking a standardized high-fat meal breakfast on Day 1. Thereafter, standard meals will be provided at 4 and 12 hours after dosing. Blood samples (5mL will be taken using an in-dwelling canula placed in the antecubital vein immediately before and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 14, and 24 hours after dosing. Subjects will be admitted for 24 hours and discharged after the last blood sampling. During the study, blood pressure and the heart rate will be monitored regularly for safety profile.

After a one week wash out period, subject will return to the ward and be given the other formulation (TRF or GDT) and the same procedures will be repeated. Any adverse events that arise during the treatment will be recorded and followed up till resolution.

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Single-site, Open-label, Dose-ranging, Efficacy, and Safety Study of EGCG/Tocotrienol in 18 Patients With Splicing-mutation-mediated CF

Eitan Kerem, MD Hadassah Medical Organization

Ongoing

Objective:
  To determine in patients with CF if oral administration of epigallocatechin gallate (EGCG) and Tocotrienol, both separate and in combination, modify CFTR splicing towards normal splicing as evaluated by improved Transepithelial Potential Difference (TEPD) assessment of chloride secretion.

Study Type: Interventional

Study Design:
Randomized, Open Label, Cross-Over Study

Subjects: Patients with cystic fibrosis

Intervention:
1) Dietary Supplement– ECGC
2) Dietary Supplement — Tocotrienol
3) Dietary Supplement — EGCG + Tocotrienol

Primary Outcome:

  • Safety and Efficacy. Changes in nasal chloride secretion as assessed by TEPD,

Secondary Outcome:

  • Pulmonary function
  • Levels of CFTR mRNA
  • Cytokine levels in sputum ­­­­­­­­­
  • TEPD measures of ion channel activity

 Methodology: Patients with CF carrying splicing mutations will be treated with EGCG 200 mg/day, Tocotrienol 600mg/day or both for 28 day cycles. Clinical parameters (TEPD, FEV1 and cytokine levels in sputum) and molecular parameters (mRNA levels,) will be analyzed to determine the effectiveness of the treatment.  In vitro studies with cell cultures derived from CF patients have shown positive results; therefore an improvement in TEPD will be an indication for CFTR expression. An increase in mRNA levels and changes in FEV1, and cytokine levels will confirm the results.

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Mechanism of Absorption and Distribution of Tocotrienols Under Different Food Status

Weng-Yew Wong, Bsc Malaysian Palm Oil Board

Completed

Objective:
Despite the emerging interest in tocotrienols, the absorption of tocotrienols in humans remains unclear especially with different fat diets. This study aimed at evaluating the absorption and distribution of tocotrienols in plasma and lipoproteins in associations with high and low fat diets. Different fat level will affect the absorption and distribution of tocotrienols.

Study Type: Interventional

Study Design: Randomized, single blind, cross-over

Subjects: Healthy Volunteers

Intervention: Tocotrienol

Primary Outcome:

  • Plasma, chylomicron, and HDL level of tocotrienol [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 24 hours after tocotrienol administration and intake of designated meal ]

Methodology: Not available

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Human Tissue Distribution of Orally Supplemented Natural Vitamin E Tocotrienol

Chandan Sen, PhD Ohio State University

Completed

Objective:
Levels of tocotrienol in human tissues following supplementation is not currently known. The objective of this present study is to determine the levels of this form of vitamin E in the human tissues such as skin, heart, lung, liver, adipose tissue, brain and cerebrospinal fluid (CSF) following oral supplementation.

Study Type: Interventional

Study Design: Non-randomized, single-blind

Subjects: 1) Healthy volunteers 2) Patients requiring surgery

Intervention: Tocotrienol, Tocopherol

Primary Outcome:

  • Measure levels of tocotrienol in the tissues of “not-healthy” subjects and in the tissue of “healthy” subjects following oral supplementation (200 mg x 2 per day for 4-24 weeks) after at least 1 month of supplementation.

Methodology: Not available

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Mechanism of Absorption and Distribution of Tocotrienols Under Different Food Status

Weng-Yew Wong, Bsc Malaysian Palm Oil Board

Completed

Objective:
Despite the emerging interest in tocotrienols, the absorption of tocotrienols in humans remains unclear especially with different fat diets. This study aimed at evaluating the absorption and distribution of tocotrienols in plasma and lipoproteins in associations with high and low fat diets. Different fat level will affect the absorption and distribution of tocotrienols.

Study Type: Interventional

Study Design: Randomized, single blind, cross-over

Subjects: Healthy Volunteers

Intervention: Tocotrienol

Primary Outcome:

  • Plasma, chylomicron, and HDL level of tocotrienol [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 24 hours after tocotrienol administration and intake of designated meal ]

Methodology: Not available

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