PRecision gerOMedicinE: Tailored Healthy agEing With Lifestyle, sUpplements and drugS (PROMETHEUS)

NCT07451496 | Recruiting

• 1 other identifier: NUS-IRB-2025-393
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

As the population ages, the growing prevalence of age-related diseases is creating substantial challenges for healthcare systems worldwide. Current therapeutic strategies often target individual diseases and decrease mortality without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process itself could prevent, delay, or manage the severity of multiple age-related diseases concurrently, thereby improving overall healthspan and reducing healthcare burdens. Emerging research highlights several interconnected hallmarks of aging, such as mitochondrial dysfunction, chronic inflammation, impaired autophagy, and immune dysregulation, as modifiable through targeted interventions. Precision geromedicine represents a paradigm shift in addressing these processes, combining baseline diagnostics with individualized treatment strategies that adapt over time based on patient response. This approach integrates lifestyle modifications, dietary supplements, and pharmacological agents to optimize physical, cognitive, and immune function across the lifespan .

Conditions

Ageing

Keywords

Whey Protein supplementation; Creatine; Fucoidan; NMN; Multivitamin; Ergothioneine; Urolithin A; Aging; Geroscience; DNA methylation; Healthspan; Epigenetic aging clock

Outcome Measures

Primary Outcomes (5)

• Change from baseline in cardiorespiratory fitness (VO₂peak)

  VO₂peak will be determined using standardized cardiopulmonary exercise testing on an electronically braked cycle ergometer

  Baseline, Week 4, and Week 8

• Change from baseline in muscle strength (one-repetition maximum (1RM))

  Change from baseline in muscle strength assessed by one-repetition maximum (1RM) testing

  Baseline, Week 4, and Week 8

• Change from baseline in muscle mass (Ultrasound imaging)

  Muscle thickness of the thigh will be assessed non-invasively using B-mode ultrasound with a linear array transducer.

  Baseline, Week 4, and Week 8

• Change from baseline in cognitive performance (NIH Toolbox Fluid Cognition Composite)

  Change from baseline in cognitive performance assessed by the NIH Toolbox Fluid Cognition Composite score.

  Baseline, Week 4, and Week 8

• Change from baseline in immune function (CD4+: CD8+ ratio)

  Change from baseline in immune status assessed by the CD4+:CD8+ T-cell ratio.

  Baseline, Week 4, and Week 8

Secondary Outcomes (20)

• Change from Baseline in Circulating Cytokines, Chemokines, and Growth Factors

  Baseline, Week 4, and Week 8

• Change from baseline in advanced glycation end-products

  Baseline, Week 4, and Week 8

• Change from baseline in methylation levels

  Baseline, Week 4, and Week 8

• Change from baseline in blood multi-omics profiles

  Baseline, Week 4, and Week 8

• Change from baseline in gut microbiome composition and fuctional capacity

  Baseline and Week 8

Other Outcomes (5)

• Study participation and retention rates

  8 weeks

• Adherence to sleep intervention

  8 weeks

• Adherence to fundamental supplementation

  8 weeks

Study Arms (2)

1 Fundamental intervention

EXPERIMENTAL

Participants receive a multimodal lifestyle intervention including sleep optimization, dietary counseling, supervised exercise with an exergaming component, motivational interviewing, and baseline nutritional supplementation.

Other: Sleep and dietary counseling; Other: Supervised exercise and exergaming program; Behavioral: Motivational interviewing; Dietary Supplement: Whey protein; Dietary Supplement: Creatine Monohydrate; Dietary Supplement: Fucoidan

2 Augmented intervention

EXPERIMENTAL

Participants receive the fundamental intervention and additional personalized supplements based on baseline muscle mass, cardiorespiratory fitness, and cognitive performance, with possible mid-study adjustment.

Other: Sleep and dietary counseling; Other: Supervised exercise and exergaming program; Behavioral: Motivational interviewing; Dietary Supplement: Whey protein; Dietary Supplement: Creatine Monohydrate; Dietary Supplement: Fucoidan; Dietary Supplement: Urolithin A; Dietary Supplement: Nicotinamide Mononucleotide (NMN); Dietary Supplement: Multivitamin; Dietary Supplement: Ergothioneine

Interventions

Sleep and dietary counseling OTHER

Sleep hygiene education and individualized dietary recommendations delivered throughout the intervention period.

1 Fundamental intervention; 2 Augmented intervention

Supervised exercise and exergaming program OTHER

Supervised dual-task cognitive-physical training with an exergaming component conducted three times per week, 60 minutes per session.

1 Fundamental intervention; 2 Augmented intervention

Motivational interviewing BEHAVIORAL

Structured motivational interviewing sessions aimed at improving adherence to lifestyle and supplementation interventions conducted two times throughout the study.

1 Fundamental intervention; 2 Augmented intervention

Whey protein DIETARY_SUPPLEMENT

Daily whey protein supplementation (GOLD STANDARD 100% ISOLATE, Optimum Nutrition) provided using a standard 30 g scoop (\~25 g protein). Dosage based on body weight: 40-59 kg: 1 scoop/day 60-89 kg: 1.5 scoops/day ≥90 kg: 2 scoops/day

1 Fundamental intervention; 2 Augmented intervention

Creatine Monohydrate DIETARY_SUPPLEMENT

Daily creatine supplementation (Micronized Creatine Monohydrate, Optimum Nutrition; 1.25 g per capsule). Dosage based on body weight: 40-59 kg: 4 capsules/day 60-89 kg: 6 capsules/day ≥90 kg: 8 capsules/day

1 Fundamental intervention; 2 Augmented intervention

Fucoidan DIETARY_SUPPLEMENT

Daily fucoidan supplementation (SIRT6Activator®, DoNotAge.org) at a dose of 2.4 g/day.

1 Fundamental intervention; 2 Augmented intervention

Urolithin A DIETARY_SUPPLEMENT

Participants below the 50th percentile for normative muscle mass receive urolithin A (StanYouth™ Urolithin A, Bonerge) at 250 mg/day.

2 Augmented intervention

Nicotinamide Mononucleotide (NMN) DIETARY_SUPPLEMENT

Participants below the 50th percentile for normative VO₂peak receive NMN (AbinoNutra® NMN, Abinopharm, Inc.) at 300 mg/day.

2 Augmented intervention

Multivitamin DIETARY_SUPPLEMENT

Participants below the 50th percentile for normative cognitive performance receive a gender-specific multivitamin (Centrum), 1 tablet daily.

2 Augmented intervention

Ergothioneine DIETARY_SUPPLEMENT

At the midpoint of the intervention (1 month), participants may receive ergothioneine (Dr.Ergo® L-ergothioneine) at 25 mg three times per week based on individual response.

2 Augmented intervention

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50-80 years (both male and female)
• Relatively healthy and in stable health condition
• Not engaged in regular resistance or aerobic training in the past 12 months (i.e., untrained)
• VO₂peak below the 75th percentile for age- and sex-specific norms
• Cognitive performance below 75th percentile on the NIH Toolbox Cognitive Function Battery
• Willing and able to comply with exercise and supplementation protocols
• English-literate (can read and understand English)
• Provides written informed consent
• Deemed to have mental capacity, as assessed by the Principal Investigator
• Are able to attend all research visits for screening and research data collection at MD11, Yong Loo Lin School of Medicine, National University of Singapore

You may not qualify if:

• Significant change in medication in the past 3 months
• History of major cardiovascular disease (e.g., coronary artery disease, heart failure, stroke)
• More than two unstable chronic conditions (e.g., hypertension, diabetes, osteoarthritis, COPD)
• Known allergies to soy, shellfish/seaweed, mushrooms, or supplement ingredients
• Participation in another interventional clinical trial
• Current use of any study-related supplement unless willing to stop
• Any medical, psychiatric, or cognitive condition deemed by the PI to jeopardise safety or compliance
• Pregnant or planning pregnancy during the study period
• Any conditions deemed by PI that jeopardize the safety or study compliance

Sponsors & Collaborators

• National University of Singapore: lead
• Xprize Foundation: collaborator
• Abinopharm, Inc: collaborator
• DoNotAge.org: collaborator

Study Sites (1)

MD11 Clinical Research Centre, #03-01, 10 Medical Drive, Singapore 117597

Singapore, Singapore, 117597, Singapore

RECRUITING

MeSH Terms

Interventions

Sleep; Nutrition Assessment; Motivational Interviewing; Whey Proteins; Creatine; fucoidan; 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; Nicotinamide Mononucleotide; Geritol; Ergothioneine

Intervention Hierarchy (Ancestors)

Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health; Directive Counseling; Counseling; Mental Health Services; Behavioral Disciplines and Activities; Health Services; Health Care Facilities Workforce and Services; Milk Proteins; Animal Proteins, Dietary; Dietary Proteins; Proteins; Amino Acids, Peptides, and Proteins; Whey; Milk; Dairy Products; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Guanidines; Amidines; Organic Chemicals; Amino Acids; Ribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Histidine; Amino Acids, Cyclic

Study Officials

• Prof. Andrea Britta Maier, MD, PhD

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajla Hodzic Kuerec, MD, PhD

CONTACT

+65 91686091; ahkuerec@nus.edu.sg

Mazzarine Dotou, PhD

CONTACT

+65 87264704; mazzarine@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oon Chiew Seng Professor in Medicine, Healthy Ageing and Dementia Research

Model Details: This is an open-label, single arm interventional feasibility study in which 20 participants (aged 50 to 80 years) will receive an 8-week multimodal precision geromedicine intervention.

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: March 5, 2026
• Study Start: September 29, 2025
• Primary Completion: February 23, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD and supporting information will become available after study completion and publication of the main findings, with the end date to be determined.
• Access Criteria: Access to de-identified IPD will be provided upon reasonable request to qualified researchers with a methodologically sound proposal and appropriate ethical approval. Requests will be reviewed by the study investigators and data will be shared under a data use agreement specifying permitted uses, data security requirements, and restrictions on re-identification.

Locations

SG (1)