Effects of MIB-626 With and Without A High-Intensity Multi-Dimensional Exercise Training Program

Healthy Clinical Trial

Official title:

Effects of MIB-626 (β-Nicotinamide Mononucleotide) With and Without A High-Intensity Multi-Dimensional Exercise Training Program on Physical Performance, Muscle Bioenergetics, and Neuropsychological Performance in Highly Fit Young Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05878119
• Other study ID #: MIB-626-206
• Status: Recruiting
• Phase: Phase 2
• Start date: October 25, 2023
• Est. completion date: June 2025

Study information

• Verified date: November 2023
• Source: Metro International Biotech, LLC
• Contact: John Gauthier
• Phone: 617-525-9136
• Email: jgauthier5[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A single-center, randomized, placebo-controlled study in community dwelling, healthy, regularly exercising, highly physically fit men and women, 19 to 40 years. Eligible participants will be randomized to receive either 1000 mg NMN or placebo twice daily for 10 weeks.

Description:

The study participants will be screened for potential participation and those meeting eligibility criteria on screening will be offered participation in the study. 120 subjects will be block randomized in a 1:1:1:1 ratio, stratified by sex (male, female) and baseline VO2 max. Participants will be randomly assigned to one of four groups using a 2 by 2 factorial design: Group 1 - MIB-626 (MIB-626 - UPA) plus usual physical activity; Group 2 - standardized, progressive, high intensity, multidimensional exercise plus placebo (PL-Ex); Group 3 - MIB-626 plus standardized, progressive, high intensity, multidimensional exercise (MIB-626-Ex); Group 4 - placebo plus usual physical activity (PL-UPA).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Highly physically fit and familiar with high intensity exercise training, as indicated

1. Engages in vigorous exercise regularly (4 or more days each week) for 30 minutes or longer and which includes elements of resistance exercise training

2. Physically fit ascertained using Daniels' equation https://runsmartproject.com/calculator/, 5K time: = 23.0 min, and/ or 10K time: = 48.0 min These criteria will maximize the likelihood of including individuals with VO2max of at least 40 mL/kg/min.

2. Has a body mass index (BMI) between 18.5 and 32 kg/m2, inclusive

3. Willingness to engage in 10-weeks of intensive exercise training designed to improve aerobic capacity and endurance, muscle strength, power, and fatigability, anaerobic capacity, and body composition, and to reduce fatigue

4. Willing to not engage in additional exercise training if randomized to the progressive exercise group and willing to not change usual physical activity if assigned to the usual physical activity group

5. Is free from clinically significant medical problems as determined by the Investigator

6. Is capable of providing written informed consent.

7. Is willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act (HIPAA).

In addition, female participants must:

1. Not be pregnant and not planning to become pregnant over the next 6 months

Exclusion Criteria:

1. Has AST or ALT > 2 times the upper limit of normal

2. Hematocrit < 36% or > 50% for men, or < 35% to > 48% for women

3. Has a diagnosis of diabetes or is using diabetes medications or has an A1C > 6.4%

4. Serum creatinine > 2.0 mg/dL or eGFR <60 mL/min

5. Prohibited medications and substances:

a. Use of any performance enhancing substance (anabolic steroids, rhGH, DHEA, androstenedione, or any other performance enhancing drug

6. Current use of opiates, amphetamine, cannabinoids and cocaine

1. Use of any other dietary supplement during the course of the trial. Subjects who are using a supplement containing nicotinamide or niacin or nicotinamide riboside may be included if they agree to stop the supplement at least 2 weeks prior to randomization and agree not to use such supplement/s during the entire duration of the study.

2. Initiation of a new pharmaceutical product during the preceding 3 months

7. Known allergy to niacin or nicotinamide mononucleotide

8. In the judgment of the study physician, the participant is unlikely to comply with the study protocol for any reason or it may not be safe to administer the study.

9. Competing in organized athletics (e.g., collegiate sports) or training in preparation for competition

10. Contraindications to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). These include: a) electrical implants such as cardiac pacemakers b) ferromagnetic implants such as aneurysm clips, surgical clips, artificial hearts valves with steel parts, shrapnel or steel implants c) ferromagnetic objects such as jewelry or metal clips in clothing d) pre-existing history of claustrophobic reactions. (Some participants who cannot undergo MRI/MRS but can undergo other study procedures might be considered on a case-by-case basis)

For women only:

1. Pregnant or planning to get pregnant over the next 6 months

2. Use of oral contraceptives is allowed provided the contraceptive regimen was initiated at least 3 months before randomization and the participant agrees not to change the regimen during the course of the study. 6.3 Excluded Medications and Treatments

1. The ingestion of the following is prohibited during 14 days prior to Day 0 and for the duration of the intervention period:

• Multivitamin preparations that contain niacin or one of its metabolites

• Products that contain niacin, nicotinic acid, nicotinamide in any form, other than natural foods

• Herbal supplements 2. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 3 month is prohibited.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Investigational Product - MIB 626
The MIB-626 will be a GMP-grade microcrystalline solid NMN mixed with inert excipients (including microcrystalline cellulose) and compressed into tablets at a dose strength of 500 mg per tablet, enabling administration of the 1,000 mg twice daily using two tablets taken twice daily.
• Placebo
Placebo - Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC

Other:
• Standardized, progressive, high intensity, multidimensional exercise
Participants will be asked to perform high intensity, standardized, progressive, multidimensional exercise.
• Usual Physical Activity
Participants will be asked to perform usual physical activity per listed in the protocol

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Metro International Biotech, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Aerobic capacity from baseline to week 11, identified as VO2 max measured during a standardized increasing work rate treadmill protocol	To determine the effects of MIB-626 (microcrystalline ß-Nicotinamide Mononucleotide), administered at a dose of 1000-mg twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on aerobic capacity, assessed as VO2 max measured during a standardized increasing work rate treadmill protocol, in community living, healthy, regularly exercising, highly physically fit, men and women, 19 to 40 years, inclusive.	11 Weeks
Secondary	Change in endurance time from baseline to week 11, measured during a constant work rate test	To determine the effects of MIB-626, administered at a dose of 1000-mg twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training, on endurance time during a constant work rate test.	11 weeks
Secondary	Change from baseline to week 11 in anaerobic threshold during CPXT	To determine the effects of MIB-626 administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on anaerobic threshold by assessing peak anaerobic power, average anaerobic capacity, rate of power decay, and fatigue index using the Wingate anaerobic power test.	11 weeks
Secondary	Change in upper body muscle performance, assessed as change from baseline to week 10	To determine the effects of MIB-626, administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on upper body muscle performance using the instrumented chest press machines (Keiser).	10 weeks
Secondary	Change in lower body muscle performance, assessed as change from baseline to week 10	To determine the effects of MIB-626, administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on lower body muscle performance using the instrumented Keiser leg press machines.	10 weeks
Secondary	Change over the 10 weeks in performance scores on sustained-attention, reaction-timed task	To determine the effects of MIB-626, administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on sustained-attention, reaction-timed task that measures the speed with which subjects respond to a visual stimulus using a standardized Psychomotor Vigilance Task test.	10 weeks
Secondary	Change over 10 weeks in working memory and working memory capacity	To determine the effects of MIB-626, administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on working memory and working memory capacity during a standardized continuous performance task assessed by using the n back test	10 weeks
Secondary	Change over 10 weeks in selective attention, target identification and response	• To determine the effects of MIB-626, administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on selective attention, target identification and response (delay in reaction time between congruent and incongruent stimuli) using the STROOP test.	10 weeks
Secondary	Change over 10 weeks in total sleep time	To determine the effects of MIB-626 administered twice daily for 10 weeks, with and without a standardized multidimensional program of progressive high intensity exercise training on total sleep time measured using an Actigraph device	10 weeks
Secondary	Change from baseline in insulin sensitivity	To determine the effects of MIB-626 on insulin sensitivity by assessing fasting glucose, insulin and a derived index of insulin sensitivity by using (HOMA-IR)	10 weeks
Secondary	Changes from baseline in blood lipid profile	To evaluate the physiologic effects of MIB-626 on blood lipid profile by assessing the levels of plasma lipids, free fatty acids, leptin, myostatin, and adiponectin in the blood.	10 weeks.
Secondary	Change from baseline in sleep latency	and without a standardized multidimensional program of progressive high intensity exercise training on sleep latency measured using an Actigraph	10 weeks