MIB-626 + Exercise for Healthy Adults

Overseen By John Gauthier

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Metro International Biotech, LLC

Must not be taking: Performance enhancers, Opiates, Amphetamines, others

Disqualifiers: Diabetes, High creatinine, MRI contraindications, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 10 weeks

120 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain supplements, especially those containing niacin or its related compounds, at least 2 weeks before starting the trial. Herbal supplements and performance-enhancing substances are also prohibited. If you're taking any of these, you'll need to stop before participating.

What data supports the effectiveness of the treatment MIB-626 + Exercise for Healthy Adults?

Research on exercise in people with multiple sclerosis (MS) shows that exercise can improve fitness, quality of life, and even have neuroprotective effects. While this research is specific to MS, it suggests that exercise, a component of the MIB-626 + Exercise treatment, can have significant health benefits. ^{1 2 3 4 5}

Is MIB-626 + Exercise safe for humans?

There is no specific safety data available for MIB-626 combined with exercise, but similar treatments like β-Nicotinamide Mononucleotide (NMN) and exercise are generally considered safe in humans. ^{6 7 8 9 10}

How does the drug MIB-626 differ from other treatments for improving physical activity in healthy adults?

MIB-626, also known as β-Nicotinamide Mononucleotide (NMN), is unique because it is a compound that may enhance cellular energy production and improve physical performance, potentially offering benefits beyond regular exercise alone. Unlike standard exercise routines, MIB-626 could provide additional support for energy metabolism, making it a novel approach for boosting physical activity in healthy adults. ^{11 12 13 14 15}

What is the purpose of this trial?

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.

Research Team

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for healthy, fit individuals aged 19-40 who regularly engage in high-intensity exercise and meet specific fitness criteria (VO2max of at least 40 mL/kg/min). Participants must have a BMI between 18.5 and 32, be willing to undergo intensive training or maintain usual activity based on group assignment, and not plan to become pregnant. Exclusions include certain medical conditions, use of performance-enhancing drugs or prohibited medications, competing athletes, and contraindications to MRI/MRS.

Inclusion Criteria

Physically fit ascertained using Daniels' equation, 5K time: ≤ 23.0 min, and/ or 10K time: ≤ 48.0 min to maximize likelihood of including individuals with VO2max of at least 40 mL/kg/min

Willingness to engage in 10-weeks of intensive exercise training

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

Exclusion Criteria

AST or ALT > 2 times the upper limit of normal

I haven't taken any forbidden substances for 14 days before starting the trial.

I have diabetes or my A1C level is above 6.4%.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either 1000 mg NMN or placebo twice daily for 10 weeks, with or without a high-intensity exercise program

10 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• High-Intensity Multi-Dimensional Exercise Training Program
• MIB-626
• Placebo
• Usual Physical Activity

Trial Overview The study tests the effects of MIB-626 (1000 mg NMN) versus placebo taken twice daily for ten weeks among highly physically fit men and women. It also examines the impact when combined with a standardized progressive high-intensity multidimensional exercise program compared to usual physical activities.

Participant Groups

Group I: Investigational Product - MIB 626 plus usual physical activity (MIB-626- UPA) Active Control 2 Interventions

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.

Group II: MIB-626 plus standardized, progressive, high intensity, multidimensional exercise (MIB-626-Ex) Active Control 2 Interventions

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.

Group III: Placebo plus usual physical activity (PL-UPA) Placebo Group 2 Interventions

Matching placebo tablets will be provided by the study's Sponsor, Metro International Biotech, LLC.

Group IV: Standardized, progressive, high intensity, multidimensional exercise plus placebo (PL-Ex) Placebo Group 2 Interventions

Matching placebo tablets will be provided by the study's Sponsor, Metro International Biotech, LLC.

Who Is Running the Clinical Trial?

Metro International Biotech, LLC

Lead Sponsor

Trials

5

Recruited

230+

Findings from Research

A 24-week intervention combining home-based exercise with essential amino acids and vitamin D significantly improved body composition and physical performance in a frail 57-year-old female with multiple sclerosis (MS).

The participant showed remarkable increases in strength and mobility, including a 67.3% improvement in gait speed and a 100% increase in the arm-curl test, indicating that this combined approach can enhance functional abilities in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the impact of exercise and essential amino acid plus cholecalciferol supplementation on physical fitness and body composition in multiple sclerosis: A case study. Ispoglou, T., Ferentinos, P., Prokopidis, K., et al.[2023]

A systematic review of 52 randomized controlled trials involving exercise interventions for people with multiple sclerosis revealed that most studies did not adequately apply key principles of exercise training, which may affect the effectiveness of the interventions.

Only 3% of the trials reported adherence to the prescribed exercise programs, highlighting a significant gap in the quality of reporting that limits the ability to reproduce results and fully understand the benefits of exercise as a treatment for multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Exercise Studies in Persons with Multiple Sclerosis: Exploring the Quality of Interventions According to the Principles of Exercise Training. Schlagheck, ML., Joisten, N., Walzik, D., et al.[2022]

A meta-analysis of 17 randomized controlled trials involving 568 participants with multiple sclerosis (MS) found that exercise training leads to a significant small reduction in fatigue, with an effect size of 0.45.

The results indicate that exercise can be an effective intervention for managing fatigue in individuals with MS, providing a potential strategy for improving their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis. Pilutti, LA., Greenlee, TA., Motl, RW., et al.[2022]

Exercise and physical activity have been shown to provide various benefits for individuals with multiple sclerosis (MS), including improvements in immune function, brain health, walking ability, cognitive performance, fatigue, depression, pain, and overall quality of life.

Despite the positive effects, there is significant variability in the outcomes of exercise interventions for MS, highlighting the need for better-designed studies and a focus on challenges in implementing effective exercise programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from clinical trials of exercise and physical activity in people with MS - guidance for improving the quality of future research. Motl, RW., Fernhall, B., McCully, KK., et al.[2022]

Recent studies indicate that exercise training can provide significant benefits for individuals with multiple sclerosis (MS), improving fitness, quality of life, and potentially reducing disability.

The review highlights the possible biological mechanisms behind these benefits, such as the role of neurotrophic factors and anti-inflammatory cytokines, suggesting that exercise may have neuroprotective effects in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment. Heesen, C., Romberg, A., Gold, S., et al.[2022]

A 3-week supplementation of 200 mg Panax ginseng did not show any significant improvement in peak aerobic exercise performance among 28 healthy young adults, as measured by various performance metrics including VO2 and exercise time.

The study suggests that Panax ginseng may not provide an ergogenic effect for enhancing aerobic performance in individuals with moderate exercise capacities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ginseng supplementation does not enhance healthy young adults' peak aerobic exercise performance. Allen, JD., McLung, J., Nelson, AG., et al.[2022]

HMB is effective in reducing exercise-induced muscle damage and enhancing recovery in both trained and untrained individuals, especially when taken close to workouts and for at least two weeks prior to exercise.

Daily consumption of 38 mg per kg of body mass can lead to increased muscle hypertrophy, strength, and power, and HMB is safe for both young and elderly populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB). Wilson, JM., Fitschen, PJ., Campbell, B., et al.[2021]

A meta-analysis of 10 randomized controlled trials involving 324 participants showed that HMB supplementation significantly reduces serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), which are markers of exercise-induced muscle damage.

The effectiveness of HMB in promoting recovery from muscle damage appears to be time-dependent, with significant benefits observed in studies lasting 6 weeks or longer, suggesting it could be a valuable recovery aid for athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis. Rahimi, MH., Mohammadi, H., Eshaghi, H., et al.[2019]

HMB supplementation has been shown to effectively reduce exercise-induced muscle damage (EIMD) by lowering markers of muscle damage, such as creatine kinase and lactate dehydrogenase, and promoting recovery.

The recommended daily intake of HMB is 3 grams, with options for chronic (≥ 2 weeks) or acute (30-60 minutes before exercise) supplementation, making it a flexible nutritional strategy for athletes to minimize muscle damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of β-hydroxy-β-methylbutyrate supplementation on recovery from exercise-induced muscle damage: a mini-review. Kim, D., Kim, J.[2023]

A single bout of endurance exercise (EE) significantly alters the kynurenine (KYN) pathway, showing stronger effects compared to resistance exercise (RE), which may help prevent harmful accumulation of KYN metabolites in the central nervous system.

The study found that the KYN/TRP ratio and levels of kynurenic acid (KA) and quinolinic acid (QA) changed after exercise, indicating that EE enhances the conversion of KYN, potentially influencing immune responses and NAD+ synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and the Kynurenine pathway: Current state of knowledge and results from a randomized cross-over study comparing acute effects of endurance and resistance training. Joisten, N., Kummerhoff, F., Koliamitra, C., et al.[2021]

In a systematic review of 36 studies involving 1561 participants, it was found that reductions in non-exercise physical activity (NEPA) and non-exercise activity thermogenesis (NEAT) occurred in 63% of diet-only, 27% of combined diet/exercise, and 23% of exercise-only intervention arms, indicating that people often compensate for weight loss efforts by becoming less active.

Participants who experienced a decrease in NEAT lost twice as much weight compared to those who did not, suggesting that the degree of energy imbalance can lead to energy conservation behaviors, although the study's limitations may affect the reliability of these conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the effect of diet and/or exercise interventions on behavioural compensation in non-exercise physical activity and related energy expenditure of free-living adults? A systematic review. Silva, AM., Júdice, PB., Carraça, EV., et al.[2023]

In a 1-year randomized controlled trial involving 80 individuals with type 2 diabetes, neither moderate-intensity continuous training (MICT) nor high-intensity interval training (HIIT) led to compensatory changes in non-exercise physical activity (NEPA) or estimated thermogenesis (NEAT) on non-training days.

Participants who were classified as low-responders or high-responders in terms of body weight and fat mass reductions did not show significant differences in NEPA or NEAT compared to control groups, indicating that exercise intensity did not affect these non-training day activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compensatory mechanisms from different exercise intensities in type 2 diabetes: a secondary analysis of a 1-year randomized controlled trial. Correia, IR., Hetherington-Rauth, M., Magalhães, JP., et al.[2023]

Physical activity improves insulin sensitivity in both healthy individuals and those with insulin resistance, with effects lasting at least 16 hours after a single exercise session due to mechanisms like increased GLUT4 transporters in muscle cells.

Regular physical training enhances insulin sensitivity even further by promoting adaptations in glucose transport and metabolism, making it a crucial strategy for preventing and treating insulin insensitivity, particularly in individuals with non-insulin-dependent diabetes mellitus (NIDDM).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and insulin sensitivity: a review. Borghouts, LB., Keizer, HA.[2022]

Regular exercise significantly increases markers of exercise capacity, such as VO2max and ventilatory threshold (VT), which can enhance overall quality of life, especially for patients with health limitations.

Exercise serves as a positive health recommendation that not only improves physical fitness but may also indirectly encourage patients to adopt healthier behaviors, contrasting with traditional negative health advice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training prescriptions for patients. Foster, C., Cadwell, K., Crenshaw, B., et al.[2019]

A 12-month exercise intervention significantly reduced intrahepatic triglyceride (IHTG) content and improved metabolic risk factors in obese patients with non-alcoholic fatty liver disease (NAFLD), with benefits lasting for up to 1 year after the intervention ended.

At the 1-year follow-up, the vigorous/moderate exercise group maintained lower waist circumference and blood pressure compared to the control group, indicating that exercise can have lasting positive effects on health even after the training period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study. Zhang, HJ., Pan, LL., Ma, ZM., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Exploring the impact of exercise and essential amino acid plus cholecalciferol supplementation on physical fitness and body composition in multiple sclerosis: A case study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Systematic Review of Exercise Studies in Persons with Multiple Sclerosis: Exploring the Quality of Interventions According to the Principles of Exercise Training. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Lessons learned from clinical trials of exercise and physical activity in people with MS - guidance for improving the quality of future research. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ginseng supplementation does not enhance healthy young adults' peak aerobic exercise performance. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB). [2021]

8. United States pubmed.ncbi.nlm.nih.gov

The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis. [2019]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Effects of β-hydroxy-β-methylbutyrate supplementation on recovery from exercise-induced muscle damage: a mini-review. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Exercise and the Kynurenine pathway: Current state of knowledge and results from a randomized cross-over study comparing acute effects of endurance and resistance training. [2021]

11. England pubmed.ncbi.nlm.nih.gov

What is the effect of diet and/or exercise interventions on behavioural compensation in non-exercise physical activity and related energy expenditure of free-living adults? A systematic review. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Compensatory mechanisms from different exercise intensities in type 2 diabetes: a secondary analysis of a 1-year randomized controlled trial. [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

Exercise and insulin sensitivity: a review. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Physical activity and exercise training prescriptions for patients. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study. [2018]