Healthy
Conditions
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.
Interventions
DIETARY_SUPPLEMENTTreatment
Each participant will receive 200mg/day of tocotrienol-rich fraction capsules divided into two daily doses
OTHERPlacebo
Participant will receive placebo softgel of 200mg divided into two daily doses
Sponsors
National University of Malaysia
Malaysia Palm Oil Board
Davos Life Science Pte Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | Baseline, Month 3 and Month 6 | Blood pressure in mmHg using Sphygmomanometer |
| Changes in Advanced Glycation End Products (AGEs) | Baseline, Month 3, and Month 6 | Changes in blood AGEs concentration measured by ELISA will be quantified as circulating glycoxidation markers and expressed in arbitrary units (AU) or µg/mL |
| Changes in Protein Carbonyl | Baseline, Month 3, and Month 6 | Change in blood protein carbonyl concentration measured by ELISA , will be quantified as nmol carbonyl/mg protein |
| Change in Malondialdehyde (MDA) | Baseline, Month 3, and Month 6 | Change in blood malondialdehyde concentration measured by high-performance liquid chromatography (HPLC) |
| Change in DNA Damage | Baseline, Month 3, and Month 6 | Change in blood DNA damage levels measured using validated laboratory assays |
| Body Composition assessment | Baseline, Month 3, and Month 6 | 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 |
| Food intake questionnaire | Baseline, Month 3, and Month 6 | 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) |
| Changes in SASP Gene expression | Baseline, Month 3, and Month 6 | Change in senescence-associated secretory phenotype (SASP) gene expression levels in peripheral blood measured by quantitative real-time polymerase chain reaction (qRT-PCR) |
| Change in SASP Protein expression | Baseline, Month 3, and Month 6 | Change in senescence-associated secretory phenotype (SASP) protein expression levels in peripheral blood measured using protein array analysis |
| Change in Tumor Necrosis Factor-Alpha (TNF-α) | Baseline, Month 3, and Month 6 | Change in blood TNF-α concentration measured by enzyme-linked immunosorbent assay (ELISA), qill be quantified in picograms per millilitre (pg/mL). |
| Change in Inteleukin-6 (IL-6) | Baseline, Month 3, and Month 6 | Change in blood IL-6 concentration measured by enzyme-linked immunosorbent assay (ELISA) |
| Change in ATP production | Baseline, Month 3, and Month 6 | Change in mitochondrial ATP production in peripheral blood measured using Seahorse analysis |
| Change in Mitochondrial Complex V Enzyme Activity | Baseline, Month 3, and Month 6 | Change in mitochondrial Complex V enzyme activity measured in peripheral blood samples |
| Change in Mitochondrial Membrane Potential | Baseline, Month 3, and Month 6 | Changes in mitochondrial membrane potential measured in peripheral blood samples |
| Change in Plasma Alpha-Tocotrienol Concentration | Baseline, Month 3, and Month 6 | Change in plasma α-tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL). |
| Change in Plasma Gamma- Tocotrienol Concentration | Baseline, Month 3, and Month 6 | Change in plasma γ-tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL). |
| Change in Total Plasma Tocotrienol Concentration | Baseline, Month 3, and Month 6 | Change in total plasma tocotrienol concentration measured by HPLC will be quantified in micromoles per litre (µmol/L) or micrograms per millilitre (µg/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle mass | Baseline and Month 6 | Appendicular lean mass in kilograms, kg will be measured using Dual-Energy X-ray Absorptiometry, (DEXA) |
| Fat mass | Baseline and Month 6 | Fat mass in gram, g will be measured using Dual-Energy X-ray Absorptiometry, (DEXA) |
| Bone mineral content (BMC) | Baseline and Month 6 | Bone mineral content in gram, g will be measured using Dual-Energy X-ray Absorptiometry, (DEXA) |
| Cognitive Function | Baseline and Month 6 | 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. |
| Recall memory function | Baseline and Month 6 | 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 |
| Working memory function | Baseline and Month 6 | 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. |
| Change in Pulse Wave Velocity (PWV) | Baseline and Month 6 | Change in arterial stiffness assessed by pulse wave velocity using an Arteriograph device, will be recorded in metres per second (m/s) |
| Change in Augmentation Index (Aix) | Baseline, and Month 6 | Change in arterial wave reflection assessed by augmentation index using an Arteriograph device will be expressed as a percentage (%). |
| Change in Central Blood Pressue | Baseline, and month 6 | Change in central blood pressure measured using an Arteriograph device will be measured in millimetres of mercury (mmHg) |
| Change in Skin Elasticity | Baseline and month 6 | Change in skin elasticity measured using a Cutometer, quantify in Arbitary unit |
| Change in Skin Hydration | Baseline and month 6 | Change in skin hydration measured using a Corneometer, quantify in Arbitary unit |
| Change in Transepidermal Water Loss | Baseline and Month 6 | Change in skin barrier function measured as transepidermal water loss using a Tewameter quantify in Arbitary unit |
| Change in Skin Pigmentation | Baseline and Month 6 | Change in skin pigmentation measured using a mexameter quantify in Arbitary unit |
| Change in sebum secretion | Baseline and Month 6 | Change in skin sebum secretion measured using a Sebumeter quantify in Arbitary unit |
| Change in Skin Wrinkle and Roughness | Baseline and Month 6 | Change in wrinkle and skin roughness parameters measured using a visiocan quantify in Arbitary unit |
Countries
Malaysia
Contacts
CONTACTSuzana Makpol
Outcome results
None listed