Targeting Aging and Promoting Longevity With Exogenous Nucleotides (TALENTs)

• ClinicalTrials.gov Identifier: NCT05243108
• Recruitment Status: Completed
• First Posted: February 16, 2022
• Last Update Posted: April 18, 2023
• Sponsor: Peking University
• Information provided by (Responsible Party): Meihong Xu, Peking University

Study Description

Brief Summary:

To investigate the effects of dietary nucleotides (NTs) as an anti-aging supplement, a clinical trial is carried as a randomized, double-blind, parallel design, placebo-controlled. A total of 120 subjects will be enrolled in the study, and they shall be randomly distributed between the two arms, NTs-treated, and placebo-control. They would be given several measurements, including physical examination, questionnaire survey, clinical and aging-related biomarkers tests at 0 (baseline), 2, and 4 months during the RCT.

Condition or disease	Intervention/treatment	Phase
Aging	Dietary Supplement: dietary nucleotides; Dietary Supplement: placebo	Not Applicable

Detailed Description:

To explore the anti-aging effects of NTs and the regulation of aging-related diseases, this study plans to recruit 120 people as subjects and conduct randomized controlled trials with NTs as an intervention for 4 months. Based on computer-generated random numbers, participants who meet the inclusion criteria are randomly assigned equally to two groups: placebo control and nucleotide intervention groups. In this study, the specific nucleotide composition is 5'-AMP、5'-CMP、5'-GMPNa2、5'-UMPNa2 prepared according to the ratio of 16:41:19:24, which is consistent with the ratio in breast milk and meets the requirements of national infant formula addition and special medical food formula. The dose of 1.2 g/day used is currently approved as the ingredient dose of nucleotides in conventional commercially available health food products. At the 0、2 and 4 months of the study, comprehensive geriatric health assessment, aging biomarker testing and biological sample collection will be conducted. Among them, the comprehensive evaluation of elderly health status is carried out by physical examination and questionnaire survey, including physical health, physiological function, quality of life, cognitive function, psychosocial health, and other aspects of information. The physical examination involves both physical assessment and functional assessment, including body composition, neck circumference, waist circumference, hip circumference, middle arm circumference, calf circumference, BMR, grip strength, six-minute walk, intima-media thickness, subcutaneous AGEs, and spirometry. The scale includes health status, nutritional status, cognitive status, physical activity, and dietary status. Blood samples were used to detect the safety and senescence-related indicators of the subjects. The index system covers four modules and seventeen dimensions, including blood routine, blood biochemistry, inflammatory factors, immune antibodies, T lymphocyte subtypes, oxidative stress level, cancer markers, leukocyte telomere length, DNA methylation, γ-H2A. Blood samples are sequenced simultaneously for gene and transcriptome sequencing. Fecal samples are collected for metagenomic sequencing of intestinal flora.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: completely randomized design
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The experiment designers used seed number 1234 to generate a random sequence of 120 random numbers on SAS software and divided the 120 random numbers into two groups based on the size of the random numbers. The larger number is Group A, and the smaller number is Group B. Both intervention drugs and placebos are produced by pharmaceutical companies without any labels and look exactly the same. Neither the trial designer nor the pharmacist participated in the trial. The researchers were responsible for recruiting subjects and assigning serial numbers according to inclusion criteria. Caregivers are responsible for dispensing, reviewing, and documenting medications. Investigators are responsible for measuring and filling out questionnaire items. Medical examinations and sample collection are carried out by hospital professionals.
• Primary Purpose: Prevention
• Official Title: A Randomized Controlled Trial Study To Evaluated the Effect of Exogenous Nucleotides as an Anti-ageing Supplement in Older Adults (60-70 Years)
• Actual Study Start Date: August 23, 2022
• Actual Primary Completion Date: March 29, 2023
• Actual Study Completion Date: March 29, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: NTs Intervention group; The subject of 1200mg has been given orally once a day for 4 months.	Dietary Supplement: dietary nucleotides; 1.2 g/d NTs (5 '-AMP, 5' -CMP, 5 '-GMPNa2, 5' -UMPNa2) ;
Placebo Comparator: placebo control group; The ingredients, dosage, and usage are the same as experimental.	Dietary Supplement: placebo; placebo

Outcome Measures

Primary Outcome Measures :

1. Phenotypic Age [ Time Frame: Baseline ]
   Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age
2. Phenotypic Age [ Time Frame: At 2 months ]
   Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age
3. Phenotypic Age [ Time Frame: At 4 months ]
   Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age
4. The levels of SOD [ Time Frame: Baseline ]
   In serum
5. The levels of SOD [ Time Frame: At 2 months ]
   In serum
6. The levels of SOD [ Time Frame: At 4 months ]
   In serum
7. The levels of GSH-Px [ Time Frame: Baseline ]
   In serum
8. The levels of GSH-Px [ Time Frame: At 2 months ]
   In serum
9. The levels of GSH-Px [ Time Frame: At 4 months ]
   In serum
10. The levels of MDA [ Time Frame: Baseline ]
    In serum
11. The levels of MDA [ Time Frame: At 2 months ]
    In serum
12. The levels of MDA [ Time Frame: At 4 months ]
    In serum
13. Carotid thickness of intima media [ Time Frame: Baseline ]
    ultrasound
14. Carotid thickness of intima media [ Time Frame: At 2 months ]
    ultrasound
15. Carotid thickness of intima media [ Time Frame: At 4 months ]
    ultrasound
16. Spontaneous fluorescence of subcutaneous AGEs [ Time Frame: Baseline ]
    AGEs test
17. Spontaneous fluorescence of subcutaneous AGEs [ Time Frame: At 2 months ]
    AGEs test
18. Spontaneous fluorescence of subcutaneous AGEs [ Time Frame: At 4 months ]
    AGEs test

Secondary Outcome Measures :

1. Body composition [ Time Frame: Baseline ]
   BIA method - fat mass (grams), lean mass (grams) and total mass (grams).
2. Body composition [ Time Frame: At 2 months ]
   BIA method - fat mass (grams), lean mass (grams) and total mass (grams).
3. Body composition [ Time Frame: At 4 months ]
   BIA method - fat mass (grams), lean mass (grams) and total mass (grams).
4. Body circumference [ Time Frame: Baseline ]
   Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference
5. Body circumference [ Time Frame: At 2 months ]
   Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference
6. Body circumference [ Time Frame: At 4 months ]
   Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference
7. Gait speed [ Time Frame: Baseline ]
   6m walking time/speed test
8. Gait speed [ Time Frame: At 2 months ]
   6m walking time/speed test.
9. Gait speed [ Time Frame: At 4 months ]
   6m walking time/speed test.
10. The score of the Short Physical Performance Battery (SPPB) [ Time Frame: Baseline ]
    The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance.
11. The score of the Short Physical Performance Battery (SPPB) [ Time Frame: At 2 months ]
    The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance.
12. The score of the Short Physical Performance Battery (SPPB) [ Time Frame: At 4 months ]
    The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance.
13. Time costs of TUG [ Time Frame: Baseline ]
    For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again.
14. Time costs of TUG [ Time Frame: At 2 months ]
    For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again.
15. Time costs of TUG [ Time Frame: At 4 months ]
    For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again.
16. Grip strength [ Time Frame: Baseline ]
    Calibrated handheld dynamometer.
17. Grip strength [ Time Frame: At 2 months ]
    Calibrated handheld dynamometer.
18. Grip strength [ Time Frame: At 4 months ]
    Calibrated handheld dynamometer.
19. Weekly physical activity Energy expenditure [ Time Frame: Baseline ]
    Activities of daily living (ADL). Weekly physical activity Energy expenditure = Physical activity intensity (MET) * time spent per day * days spent per week (MET= METn HN/h), According to the International Physical Activity Scale (IPAQ), the elderly were divided into three levels of physical activity: low (less than 600 METs/ week), medium (600~3 000 METs/ week) and high (over 3 000 METs/ week)
20. Weekly physical activity Energy expenditure [ Time Frame: At 4 months ]
    Activities of daily living (ADL). Weekly physical activity Energy expenditure = Physical activity intensity (MET) * time spent per day * days spent per week (MET= METn HN/h), According to the International Physical Activity Scale (IPAQ), the elderly were divided into three levels of physical activity: low (less than 600 METs/ week), medium (600~3 000 METs/ week) and high (over 3 000 METs/ week)
21. Pittsburgh sleep quality index (PSQI) [ Time Frame: Baseline ]
    Items are categorized into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication, and daytime dysfunction. The possible score range for each component is 0 (no difficulty) to 3 (severe difficulty). The seven component scores are summed to produce a global score; higher scores represent poorer subjective sleep quality.
22. Pittsburgh sleep quality index (PSQI) [ Time Frame: At 4 months ]
    Items are categorized into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication, and daytime dysfunction. The possible score range for each component is 0 (no difficulty) to 3 (severe difficulty). The seven component scores are summed to produce a global score; higher scores represent poorer subjective sleep quality.
23. Score of Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline ]
    Scores range from 0-30 (+1 for 12 or fewer years of education); a score of 26 or higher indicates normal cognitive functioning, while a score of 25 or lower indicates impaired functioning.
24. Score of Montreal Cognitive Assessment (MoCA) [ Time Frame: At 4 months ]
    Scores range from 0-30 (+1 for 12 or fewer years of education); a score of 26 or higher indicates normal cognitive functioning, while a score of 25 or lower indicates impaired functioning.
25. The levels of TNF-α in serum [ Time Frame: Baseline ]
    Suspension array
26. The levels of TNF-α in serum [ Time Frame: At 4 months ]
    Suspension array
27. The levels of IL-1 in serum [ Time Frame: Baseline ]
    Suspension array
28. The levels of IL-1 in serum [ Time Frame: At 4 months ]
    Suspension array
29. The levels of IL-6 in serum [ Time Frame: Baseline ]
    Suspension array
30. The levels of IL-6 in serum [ Time Frame: At 4 months ]
    Suspension array
31. The levels of MCP-1 in serum [ Time Frame: Baseline ]
    Suspension array
32. The levels of MCP-1 in serum [ Time Frame: At 4 months ]
    Suspension array
33. The levels of ICAM-1 in serum [ Time Frame: Baseline ]
    Suspension array
34. The levels of ICAM-1 in serum [ Time Frame: At 4 months ]
    Suspension array
35. Methylation damage [ Time Frame: Baseline ]
    Blood sample
36. Methylation damage [ Time Frame: At 4 months ]
    Blood sample
37. The level of telomere repeat binding factors-1 (TRF-1) [ Time Frame: Baseline ]
    Blood sample
38. The level of telomere repeat binding factors-1 (TRF-1) [ Time Frame: At 4 months ]
    Blood sample
39. The level of telomere repeat binding factors-2 (TRF-2) [ Time Frame: Baseline ]
    Blood sample
40. The level of telomere repeat binding factors-2 (TRF-2) [ Time Frame: At 4 months ]
    Blood sample
41. The length of Leukocyte telomere [ Time Frame: Baseline ]
    Blood sample
42. The length of Leukocyte telomere [ Time Frame: At 4 months ]
    Blood sample

Other Outcome Measures:

1. Gut microbiota [ Time Frame: Baseline ]
   Total bacterial DNA was extracted from fecal samples, followed by 16S-targeted amplification, high-throughput sequencing, species annotation and abundance analysis to describe the intestinal microecological structure and diversity of the subjects
2. Gut microbiota [ Time Frame: At 4 months ]
   Total bacterial DNA was extracted from fecal samples, followed by 16S-targeted amplification, high-throughput sequencing, species annotation and abundance analysis to describe the intestinal microecological structure and diversity of the subjects
3. Scores of Quality of life [ Time Frame: Baseline ]
   Quality of life was measured 36-Item Short Form Survey (SF-12) questionnaire. The items are grouped into eight domain scores: physical functioning, role limitations due to physical health, pain, general health, energy, social functioning, role limitations due to emotional problems and emotional well-being. Domain scores can be collapsed to a physical component summary Physical health (PCS) and a mental component summary Mental health (MHS). Each score ranges from 0 to 100, with higher values representing the better self-perceived health-related quality of life.
4. Scores of Quality of life [ Time Frame: At 4 months ]
   Quality of life was measured 36-Item Short Form Survey (SF-12) questionnaire. The items are grouped into eight domain scores: physical functioning, role limitations due to physical health, pain, general health, energy, social functioning, role limitations due to emotional problems and emotional well-being. Domain scores can be collapsed to a physical component summary Physical health (PCS) and a mental component summary Mental health (MHS). Each score ranges from 0 to 100, with higher values representing the better self-perceived health-related quality of life.
5. Nutrition condition [ Time Frame: Baseline ]
   Nutrition condition was measured by MNA-SF questionaire. 12 to 14 points of normal nutritional status; 8 to 11 are at risk of malnutrition; 0 to 7 points malnutrition
6. Nutrition condition [ Time Frame: At 4 months ]
   Nutrition condition was measured by MNA-SF questionaire. 12 to 14 points of normal nutritional status; 8 to 11 are at risk of malnutrition; 0 to 7 points malnutrition

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male/females of 60 to 70 years of age
2. No serious physical or mental illness
3. Able to provide written Informed Consent
4. Able to follow verbal and written study directions
5. Must not be taking or be willing to take any supplements containing any form of nucleotides for one year prior to baseline and for the duration of the study.
6. Able to maintain consistent diet and lifestyle habits throughout the study
7. Willing to consume assigned supplement (NTs or placebo) for 4 months

Exclusion Criteria:

1. Participants on the current use of prescription or over-the-counter nucleotides
2. Having abnormal screening laboratory test values or other lab test result(s) that would preclude study participation in the judgment of the investigator
3. Documented presence of atherosclerotic disease and/or cardiopulmonary disease
4. History of drug or alcohol abuse
5. History of unstable depression or mental illness within the last 6 months for which the investigator believes could impact the participant's ability to comply with study requirements
6. Other diseases or medications, according to the investigator, that would interfere directly in the results of the study or jeopardize the health of the participant.
7. Currently, or within the past 30 days, enrolled in a different clinical investigation
8. Inability to provide a venous blood sample
9. Unable or unwilling to provide written informed consent for participation in the study

Contacts and Locations

Locations

China, Sichuan

Talents project team

Chengdu, Sichuan, China, 610095

Sponsors and Collaborators

Peking University

Investigators

• Principal Investigator: Meihong Xu, Assis prof.; Peking University

More Information

• Responsible Party: Meihong Xu, Associate professor, Peking University
• ClinicalTrials.gov Identifier: NCT05243108
• Other Study ID Numbers: TALENTs
• First Posted: February 16, 2022
• Last Update Posted: April 18, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Meihong Xu, Peking University:

anti-aging; telomerase