Tocotrienol Supplementa as A Senolytic Agent in Middle-aged Adults

NCT07637487 | Recruiting DMC

• 1 other identifier: UKM PPI/111/8/JEP-2022-676
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine whether tocotrienol works as a senolytic agent to delay age-related biological changes in middle-aged adults. The study will also evaluate the safety of tocotrienol supplementation. The main questions it aims to answer are: Does tocotrienol reduce markers of cellular senescence, inflammation, oxidative stress, and mitochondrial dysfunction? What health changes or medical issues occur in participants taking tocotrienol? Researchers will compare tocotrienol-rich fraction to a placebo (a look-alike capsule with no active ingredient) to determine whether tocotrienol is effective in modulating aging-related pathways. Participants will: Take tocotrienol (200 mg/day) or a placebo daily for 6 months Attend study visits at baseline, 3 months, and 6 months for clinical assessments and laboratory tests Undergo blood sampling and health evaluations, including measures of senescence-associated secretory phenotype (SASP), inflammation, oxidative stress, mitochondrial function, vascular health, skin status, cognitive function, body composition, and bone mineral density. Complete questionnaires related to diet throughout the study period This study aims to provide clinical evidence on the potential of tocotrienol as a senolytic intervention for promoting healthy aging and reducing the risk of age-related diseases.

Conditions

Healthy

Outcome Measures

Primary Outcomes (17)

• Blood pressure

  Blood pressure in mmHg using Sphygmomanometer

  Baseline, Month 3 and Month 6

• Changes in Advanced Glycation End Products (AGEs)

  Changes in blood AGEs concentration measured by ELISA will be quantified as circulating glycoxidation markers and expressed in arbitrary units (AU) or µg/mL

  Baseline, Month 3, and Month 6

• Changes in Protein Carbonyl

  Change in blood protein carbonyl concentration measured by ELISA , will be quantified as nmol carbonyl/mg protein

  Baseline, Month 3, and Month 6

• Change in Malondialdehyde (MDA)

  Change in blood malondialdehyde concentration measured by high-performance liquid chromatography (HPLC)

  Baseline, Month 3, and Month 6

• Change in DNA Damage

  Change in blood DNA damage levels measured using validated laboratory assays

  Baseline, Month 3, and Month 6

• Body Composition assessment

  Measured using Inbody 770 Analyzer at Physiology Department; BMI (kg/m²) calculated from weight (kg) and height (m); Body fat percentage (%); visceral fate (cm²); basal metabolic rate (kcal); waist to hip ratio

  Baseline, Month 3, and Month 6

• Food intake questionnaire

  Food frequency questionnaires (FFQ) will be completed by the participants, and analyse through Diet Information Management System; Result reported for carbohydrate (g), Cholesterol (mg), Energy (kcal), Fat (g), Fibre (g), Protein (g), vitamin E (mg), water (g)

  Baseline, Month 3, and Month 6

• Changes in SASP Gene expression

  Change in senescence-associated secretory phenotype (SASP) gene expression levels in peripheral blood measured by quantitative real-time polymerase chain reaction (qRT-PCR)

  Baseline, Month 3, and Month 6

• Change in SASP Protein expression

  Change in senescence-associated secretory phenotype (SASP) protein expression levels in peripheral blood measured using protein array analysis

  Baseline, Month 3, and Month 6

• Change in Tumor Necrosis Factor-Alpha (TNF-α)

  Change in blood TNF-α concentration measured by enzyme-linked immunosorbent assay (ELISA), qill be quantified in picograms per millilitre (pg/mL).

  Baseline, Month 3, and Month 6

• Change in Inteleukin-6 (IL-6)

  Change in blood IL-6 concentration measured by enzyme-linked immunosorbent assay (ELISA)

  Baseline, Month 3, and Month 6

• Change in ATP production

  Change in mitochondrial ATP production in peripheral blood measured using Seahorse analysis

  Baseline, Month 3, and Month 6

• Change in Mitochondrial Complex V Enzyme Activity

  Change in mitochondrial Complex V enzyme activity measured in peripheral blood samples

  Baseline, Month 3, and Month 6

• Change in Mitochondrial Membrane Potential

  Changes in mitochondrial membrane potential measured in peripheral blood samples

  Baseline, Month 3, and Month 6

• Change in Plasma Alpha-Tocotrienol Concentration

  Change in plasma α-tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL).

  Baseline, Month 3, and Month 6

• Change in Plasma Gamma- Tocotrienol Concentration

  Change in plasma γ-tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL).

  Baseline, Month 3, and Month 6

• Change in Total Plasma Tocotrienol Concentration

  Change in total plasma tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL).

  Baseline, Month 3, and Month 6

Secondary Outcomes (15)

• Muscle mass

  Baseline and Month 6

• Fat mass

  Baseline and Month 6

• Bone mineral content (BMC)

  Baseline and Month 6

• Cognitive Function

  Baseline and Month 6

• Recall memory function

  Baseline and Month 6

Study Arms (2)

Investigational product (IP)

EXPERIMENTAL

Participant receiving investigational product at 200mg daily

Dietary Supplement: Treatment

Placebo

PLACEBO COMPARATOR

Participant receiving placebo capsules at 200mg daily

Other: Placebo

Interventions

Treatment DIETARY_SUPPLEMENT

Each participant will receive 200mg/day of tocotrienol-rich fraction capsules divided into two daily doses

Investigational product (IP)

Placebo OTHER

Participant will receive placebo softgel of 200mg divided into two daily doses

Placebo

Eligibility Criteria

• Age: 35 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Generally healthy as assessed by physical examination and blood lab test, including adequate liver and renal function, Neutrophil count \> 1500/mm3, Platelet count 120,000 - 450,000/mm3, Haemoglobin concentration 11.5 to 19.0g/dL for men; 10.5-17.5 g/dL for women, Prothrombin and partial thromboplastin time within normal range, ALT and AST \< 80 IU/L, Creatinine 0.7 to 1.3 mg/dL
• Subject of either gender, 35 to 64 years of age (inclusive)
• Not allergy to palm oil and vitamin E
• Do not take vitamin E supplements over the past 3 months
• Provide written informed consent prior to screening
• Subject is willing and able to comply with the study visit schedule and procedure, geographic proximity (investigator's discretion) that allows adequate follow up
• Subjects understand the study protocol and signed informed consent forms

You may not qualify if:

• Subjects with fat malabsorption
• Subjects with chronic conditions such as cardiac diseases (heart failure, myocardial infraction, ischemic heart disease), neurological diseases, diabetes, HIV infection, psychiatric illness/social situations
• Subjects with vegan diet
• Current smoker or used to smoke in the past 3 months
• Subject for surgery or had undergone surgery in the past 3 months
• Current or past history of drug, alcohol abuse and cancer
• Pregnant and lactating women
• History of bleeding tendencies or any condition predisposing to bleeding e.g. thrombocytopenia, abnormal liver function, liver disease (e.g. chronic hepatitis), gastrointestinal ulcers
• Any subject taking antibiotics or other medication or dietary supplement which could interfere with the action of tocotrienols
• Subjects who are pre-disposed to inherited blood/circulation disorders
• Subject who is taking anticoagulants and antithrombotic drugs, e.g. warfarin, aspirin, ticlopidine, heparin, etc.

Sponsors & Collaborators

• National University of Malaysia: lead
• Malaysia Palm Oil Board: collaborator
• Davos Life Science Pte Ltd: collaborator

Study Sites (1)

National University of Malaysia

Kuala Lumpur, Kuala Lumpur, 56000, Malaysia

RECRUITING

MeSH Terms

Interventions

Therapeutics

Central Study Contacts

Suzana Makpol

CONTACT

603-91459554; suzanamakpol@ukm.edu.my

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: June 9, 2026
• Study Start: October 31, 2023
• Primary Completion: December 19, 2024
• Study Completion (Estimated): January 30, 2027
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 1 year after publication and ending 3 years after the publication of results
• Access Criteria: The Principal Investigator will review the request

Locations

MY (1)