Slow Age: Interventions to Slow Aging in Humans

NCT05593939 | Completed Phase 2

• 1 other identifier: H-21017723
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The proportion of older individuals is growing, and it is therefore important to investigate ways to promote healthy aging. Exercise is one of the most studied interventions and is known to have a variety of health benefits. Dietary interventions have also shown encouraging results, with intermittent fasting being a promising anti-aging intervention. Likewise, dietary supplementation with precursors that can increase the central metabolite nicotinamide dinucleotide (NAD+) has powerful effects on aging at least in model organisms. Although physical exercise is known to increase health-span, the effects of these latter dietary interventions on aging lacks evidence in humans. This is a randomized, controlled trial of interventions to slow aging in humans. Healthy older individuals will be randomized into either an aerobic exercise (EXE), time-restricted feeding (TRF), nicotinamide riboside (NR), or control group and followed for twelve weeks. Changes in biomarkers of aging will be assessed before and after the intervention. It is hypothesized that the interventions provide similar, superior benefits to these markers when compared to placebo. Primary Outcome: Interleukin-6 levels. Secondary Outcomes: CRP, TNF-α, NAD+, hematologic age, epigenetic age (DNA methylation), transcriptomic age (RNA-sequencing), functional age (handgrip strength, gait speed), body composition, vocal age, and photo age

Conditions

Aging

Outcome Measures

Primary Outcomes (1)

• Interleukin-6 levels in plasma

  Day 1 compared to day 84

Secondary Outcomes (12)

• Concentration of CRP in plasma

  Day 1 compared to day 84

• Concentration of TNF-α in plasma

  Day 1 compared to day 84

• Concentration of NAD in whole blood

  Day 1 compared to day 84

• Change in fat mass

  Day 1 compared to day 84

• Change in lean mass

  Day 1 compared to day 84

Study Arms (4)

Exercise arm

EXPERIMENTAL

12 week aerobic exercise will be performed in agreement with current guidelines for exercise in older adults from the American College of Sports Medicine. A frequency of 5 days/week, totaling 150-300 min/week, performed at both moderate and vigorous intensities is chosen. This dose has a high level of evidence supporting positive effects on health- and life-span.

Behavioral: Exercise

Time restricted feeding

EXPERIMENTAL

A 12 week fasting/feeding regiment of 16 hours fasting /8 hours feeding each day is chosen. This ratio has been shown to be tolerable in older individuals.

Behavioral: Time restricted feeding

Nicotinamide riboside

EXPERIMENTAL

Previous clinical trials have shown that an nicotinamide riboside dose up to 2 g/day is well tolerated with no treatment-emergent adverse events reported so far and with efficacy on our primary outcome measurement. A dose of 2 g/day NR is therefore chosen and will be split in two: 1 g in the morning and 1 g in the evening.

Dietary Supplement: Nicotinamide riboside

Control

NO INTERVENTION

A control group with no intervention.

Interventions

Exercise BEHAVIORAL

Participants randomized to the EXE group will perform aerobic exercise five days per week, totaling 150-300 min/week, at moderate to vigorous intensities i.e., \~60-90% heart rate (HR) max. Participants randomized to the EXE group will perform aerobic exercise five days per week, totaling 150-300 min/week, at moderate to vigorous intensities i.e., \~60-90% heart rate (HR) max. Exercise intensity and duration will gradually increase up until week 3 to habituate the participants to the exercise. The training modality will change to reduce the risk of injuries and may be impacted by individual preferences to increase adherence. The training can be performed individually or in groups of 4-6 participants, depending on the geographical locations of the participants home address, and on the current recruitment rate.

Exercise arm

Time restricted feeding BEHAVIORAL

Participants randomized to the time restricted feeding group will be instructed to abstain from any caloric intake during the targeted fasting window of 16 continuous hours and consume ad libitum during the eating window of 8 hours.

Time restricted feeding

Nicotinamide riboside DIETARY_SUPPLEMENT

Participants randomized to the NR group will be instructed to take the administered tablets once in the morning (1 g) and once in the evening (1 g), in both cases with a meal.

Nicotinamide riboside

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Aged ≥ 65 years
• In good general health

You may not qualify if:

• Inability or unwillingness to take oral supplements
• Inability or unwillingness to adhere to the fasting regiment
• Inability or unwillingness to perform the prescribed physical exercise
• Current smoker or use of any nicotine products within 10 years
• Chronic use of supplements containing vitamin B or nicotinamide riboside
• Treatment with another investigational drug or other intervention within 1 year
• Cancer diagnosis within last 5 years

Sponsors & Collaborators

• University of Copenhagen: lead
• Elysium Health: collaborator

Study Sites (1)

University of Copenhagen

Copenhagen, 2200, Denmark

Location

MeSH Terms

Interventions

Exercise; nicotinamide-beta-riboside

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 26, 2022
• Study Start: May 1, 2022
• Primary Completion: December 21, 2022
• Study Completion: December 21, 2022
• Last Updated: April 25, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)