Tocotrienol Supplementa as A Senolytic Agent in Middle-aged Adults

Official title

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

Overview

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.

Interventions

• Dietary supplement Treatment
  Each participant will receive 200mg/day of tocotrienol-rich fraction capsules divided into two daily doses
• Other Placebo
  Participant will receive placebo softgel of 200mg divided into two daily doses

Primary outcome measures

• Blood pressure [Time frame: Baseline, Month 3 and Month 6]
• Changes in Advanced Glycation End Products (AGEs) [Time frame: Baseline, Month 3, and Month 6]
• Changes in Protein Carbonyl [Time frame: Baseline, Month 3, and Month 6]
• Change in Malondialdehyde (MDA) [Time frame: Baseline, Month 3, and Month 6]
• Change in DNA Damage [Time frame: Baseline, Month 3, and Month 6]
• Body Composition assessment [Time frame: Baseline, Month 3, and Month 6]
• Food intake questionnaire [Time frame: Baseline, Month 3, and Month 6]
• Changes in SASP Gene expression [Time frame: Baseline, Month 3, and Month 6]
• Change in SASP Protein expression [Time frame: Baseline, Month 3, and Month 6]
• Change in Tumor Necrosis Factor-Alpha (TNF-α) [Time frame: Baseline, Month 3, and Month 6]

Secondary outcome measures (12)

• Muscle mass [Time frame: Baseline and Month 6]
• Fat mass [Time frame: Baseline and Month 6]
• Bone mineral content (BMC) [Time frame: Baseline and Month 6]
• Cognitive Function [Time frame: Baseline and Month 6]
• Recall memory function [Time frame: Baseline and Month 6]
• Working memory function [Time frame: Baseline and Month 6]
• Change in Pulse Wave Velocity (PWV) [Time frame: Baseline and Month 6]
• Change in Augmentation Index (Aix) [Time frame: Baseline, and Month 6]
• Change in Central Blood Pressue [Time frame: Baseline, and month 6]
• Change in Skin Elasticity [Time frame: Baseline and month 6]
• Change in Skin Hydration [Time frame: Baseline and month 6]
• Change in Transepidermal Water Loss [Time frame: Baseline and Month 6]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

Malaysia · 1 center

• National University of Malaysia — Kuala Lumpur

Identifiers

NCT: NCT07637487 · UKM PPI/111/8/JEP-2022-676

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗