Tocotrienol Supplementa as A Senolytic Agent in Middle-aged Adults

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Evaluating Tocotrienol-Rich Fraction as a Senolytic Agent in Middle-Aged Adults

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Treatment; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suzana Makpol; Phone Number: 603-91459554; Email: suzanamakpol@ukm.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 56000
      • Recruiting
      • National University of Malaysia
      • Contact: Suzana Makpol; Phone Number: 603-91459554; Email: suzanamakpol@ukm.edu.my

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational product (IP); Participant receiving investigational product at 200mg daily	Dietary supplement: Treatment; Each participant will receive 200mg/day of tocotrienol-rich fraction capsules divided into two daily doses
Placebo Comparator: Placebo; Participant receiving placebo capsules at 200mg daily	Other: Placebo; Participant will receive placebo softgel of 200mg divided into two daily doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle mass	Appendicular lean mass in kilograms, kg will be measured using Dual-Energy X-ray Absorptiometry, (DEXA)	Baseline and Month 6
Fat mass	Fat mass in gram, g will be measured using Dual-Energy X-ray Absorptiometry, (DEXA)	Baseline and Month 6
Bone mineral content (BMC)	Bone mineral content in gram, g will be measured using Dual-Energy X-ray Absorptiometry, (DEXA)	Baseline and Month 6
Cognitive Function	The assessment instrument, the Montreal Cognitive Assessment (MoCA) test will be administered. The evaluation involves assessing participants through questions and instructions covering executive and spatial cognitive domains. The maximum score is 30. A score of 26 and above indicates no cognitive impairment.	Baseline and Month 6
Recall memory function	The Rey Auditory Verbal Learning Test (RAVLT) will be utilized. the RAVLT includes two distinct word lists (A and B). Participants will recall the items from list A over five trials (Memory A1 to A5). Following this, an interference list (list B), comprising 15 unrelated nouns, will be introduced, and participants will attempt to recall as many words as possible from it. Subsequently, participants will be asked to recall the words from list A (Delayed recall/memory A6) without the examiner repeating the list. The number of correctly recalled words for each trial will be totaled to generate a score. Total Learning Score (Sum of Trials A1-A5) to indicate normal performance: 45-65, Mild Cognitive impairment: 30-45, dementia: below 30. For delayed recall score (M6), to indicate normal performance: ≥8-12 words recalled, Mild Cognitive Impairment: 4-7 words recalled, and dementia: ≤3 words recalled	Baseline and Month 6
Working memory function	The Digit Span Test involves recalling numbers in the same order (forward), reverse order (backward), or ascending order (sequencing). The test starts with short sequences and increases in length to assess memory capacity. A higher score (20 - 30) indicates better cognitive function, while a lower score (0 - 19) may suggest attention or memory issues. The total score is 30.	Baseline and Month 6
Change in Pulse Wave Velocity (PWV)	Change in arterial stiffness assessed by pulse wave velocity using an Arteriograph device, will be recorded in metres per second (m/s)	Baseline and Month 6
Change in Augmentation Index (Aix)	Change in arterial wave reflection assessed by augmentation index using an Arteriograph device will be expressed as a percentage (%).	Baseline, and Month 6
Change in Central Blood Pressue	Change in central blood pressure measured using an Arteriograph device will be measured in millimetres of mercury (mmHg)	Baseline, and month 6
Change in Skin Elasticity	Change in skin elasticity measured using a Cutometer, quantify in Arbitary unit	Baseline and month 6
Change in Skin Hydration	Change in skin hydration measured using a Corneometer, quantify in Arbitary unit	Baseline and month 6
Change in Transepidermal Water Loss	Change in skin barrier function measured as transepidermal water loss using a Tewameter quantify in Arbitary unit	Baseline and Month 6
Change in Skin Pigmentation	Change in skin pigmentation measured using a mexameter quantify in Arbitary unit	Baseline and Month 6
Change in sebum secretion	Change in skin sebum secretion measured using a Sebumeter quantify in Arbitary unit	Baseline and Month 6
Change in Skin Wrinkle and Roughness	Change in wrinkle and skin roughness parameters measured using a visiocan quantify in Arbitary unit	Baseline and Month 6

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Malaysia Palm Oil Board; Davos Life Science Pte Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Actual): December 19, 2024
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics
• Other Study ID Numbers: UKM PPI/111/8/JEP-2022-676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: Beginning 1 year after publication and ending 3 years after the publication of results
• IPD Sharing Access Criteria: The Principal Investigator will review the request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No