Slow Age: Interventions to Slow Aging in Humans (SlowAge)

• ClinicalTrials.gov Identifier: NCT05593939
• Recruitment Status: Completed
• First Posted: October 26, 2022
• Last Update Posted: April 25, 2023
• Sponsor: University of Copenhagen
• Collaborator: Elysium Health
• Information provided by (Responsible Party): University of Copenhagen

Study Description

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

Condition or disease	Intervention/treatment	Phase
Aging	Behavioral: Exercise; Behavioral: Time restricted feeding; Dietary Supplement: Nicotinamide riboside	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Slow Age: a Randomized, Controlled Clinical Trial of Interventions to Slow Aging in Humans
• Actual Study Start Date: May 1, 2022
• Actual Primary Completion Date: December 21, 2022
• Actual Study Completion Date: December 21, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exercise arm; 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; 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.
Experimental: Time restricted feeding; 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; 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.
Experimental: Nicotinamide riboside; 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; 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.
No Intervention: Control; A control group with no intervention.

Outcome Measures

Primary Outcome Measures :

1. Interleukin-6 levels in plasma [ Time Frame: Day 1 compared to day 84 ]

Secondary Outcome Measures :

1. Concentration of CRP in plasma [ Time Frame: Day 1 compared to day 84 ]
2. Concentration of TNF-α in plasma [ Time Frame: Day 1 compared to day 84 ]
3. Concentration of NAD in whole blood [ Time Frame: Day 1 compared to day 84 ]
4. Change in fat mass [ Time Frame: Day 1 compared to day 84 ]
   Measured using bio-impedance
5. Change in lean mass [ Time Frame: Day 1 compared to day 84 ]
   Measured using bio-impedance
6. Grip strength [ Time Frame: Day 1 compared to day 84 ]
7. Gait speed [ Time Frame: Day 1 compared to day 84 ]
   Measured over 4 meters.
8. Predicted age (DNA methylation) [ Time Frame: Day 1 compared to day 84 ]
   From PBMCs
9. Predicted age (Blood age) [ Time Frame: Day 1 compared to day 84 ]
   From 33 blood parameters
10. Predicted age (Transcriptomics) [ Time Frame: Day 1 compared to day 84 ]
    From RNA seq of PBMCs
11. Predicted age (voice) [ Time Frame: Day 1 compared to day 84 ]
    From voice recordings
12. Predicted age (photo) [ Time Frame: Day 1 compared to day 84 ]
    From a portrait photo

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

Denmark

University of Copenhagen

Copenhagen, Denmark, 2200

Sponsors and Collaborators

University of Copenhagen

Elysium Health

More Information

• Responsible Party: University of Copenhagen
• ClinicalTrials.gov Identifier: NCT05593939
• Other Study ID Numbers: H-21017723
• First Posted: October 26, 2022
• Last Update Posted: April 25, 2023
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: This is not possible under current data protection rules.

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

Additional relevant MeSH terms:

Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents