Gamma-delta Tocotrienol as Potential Maintenance Treatment in Women With Metastatic Breast Cancer

Healthy Subjects Clinical Trial

— GEMM1a  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01571921
• Other study ID #: 896.128
• Status: Completed
• Phase: Phase 1
• First received: March 26, 2012
• Last updated: September 13, 2016
• Start date: January 2013
• Est. completion date: February 2013

Study information

• Verified date: September 2016
• Source: Malaysia Palm Oil Board
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malaysia: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Twelve healthy volunteers who fit the inclusion and exclusion criteria and provide written informed consent to participate in the trial will be recruited to compare the rate and extent of absorption and pharmacokinetics of the newly formulated Gamma-Delta formulation with TRF.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male and female aged 21-55 years old

• Good health

• No allergy to vitamin E/ palm oil

• No past (within 3 months) / current use of dietary supplements containing vitamin E

Exclusion Criteria:

• History of bleeding tendencies or any condition predisposing to bleeding e.g. thrombocytopenia, abnormal liver function, liver disease (e.g. chronic hepatitis), gastrointestinal ulcers

• Candidate for surgery or had undergone surgery in the past 6 months

• Current or past use (last 3 months) of antithrombotic drugs such as antiplatelets (aspirin, ticlopidine), anticoagulants (heparin, warfarin), thrombolytic agents (streptokinase), etc

• Current or past history of cancer

• Pregnant/ breastfeeding women

• Smokers

• Drug or alcohol abuse

• Hypercholesterolemia

• Chronic conditions such as uncontrolled hypertension, heart disease (ischemic heart disease, heart failure, cardiac arrhythmia), uncontrolled diabetes, HIV infection, or other psychiatric illness/ social situations that might limit adherence to study protocol.

• Unable or unwilling to stop taking vitamins, herbal preparations or nonprescription medications

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Dietary Supplement:
• Gamma-Delta Tocotrienol and Tocotrienol Rich Fraction
Single oral TRF or Gamma-Delta Tocotrienol dosage

Locations

Country	Name	City	State
Malaysia	University Malaya Medical Centre(UMMC)	Lembah Pantai,	Kuala Lumpur

Sponsors (2)

Lead Sponsor	Collaborator
Malaysia Palm Oil Board	University of Malaya

Country where clinical trial is conducted

Malaysia, 

References & Publications (6)

Comitato R, Nesaretnam K, Leoni G, Ambra R, Canali R, Bolli A, Marino M, Virgili F. A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction. Am J Physiol Endocrinol Metab. 2009 Aug;297(2):E427-37. doi: 10.1152/ajpendo.00187.2009. Epub 2009 Jun 2. — View Citation

Mahalingam D, Radhakrishnan AK, Amom Z, Ibrahim N, Nesaretnam K. Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers. Eur J Clin Nutr. 2011 Jan;65(1):63-9. doi: 10.1038/ejcn.2010.184. Epub 2010 Sep 22. — View Citation

Nesaretnam K, Selvaduray KR, Abdul Razak G, Veerasenan SD, Gomez PA. Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial. Breast Cancer Res. 2010;12(5):R81. doi: 10 — View Citation

Patel V, Rink C, Gordillo GM, Khanna S, Gnyawali U, Roy S, Shneker B, Ganesh K, Phillips G, More JL, Sarkar A, Kirkpatrick R, Elkhammas EA, Klatte E, Miller M, Firstenberg MS, Chiocca EA, Nesaretnam K, Sen CK. Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. J Nutr. 2012 Mar;142(3):513-9. doi: 10.3945/jn.111.151902. Epub 2012 Feb 1. — View Citation

Weng-Yew W, Selvaduray KR, Ming CH, Nesaretnam K. Suppression of tumor growth by palm tocotrienols via the attenuation of angiogenesis. Nutr Cancer. 2009;61(3):367-73. doi: 10.1080/01635580802582736. — View Citation

Zaiden N, Yap WN, Ong S, Xu CH, Teo VH, Chang CP, Zhang XW, Nesaretnam K, Shiba S, Yap YL. Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion. J Atheroscler Thromb. 2010 Oct 27;17(10):1019-32. Epub 2010 Aug 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration (Cmax)of drug		0 to 24 hours after dosing	No