Azithromycin Impact on Exercise Performance

Recruiting at 1 trial location

Overseen By Daniel D DeSio, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rutgers, The State University of New Jersey

Must be taking: Hormonal contraceptives

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Heart disease, Hypertension, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 5 days

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The gut microbiome refers to the trillions of bacteria that inhabit the stomach and other regions involved in the digestion of food, including the intestines. Compelling studies of animals (rodents) suggest that the health of the gut microbiome may influence skeletal muscle function and exercise performance. To date, there have been no similar observations reported in humans. A common experimental approach in animal studies to temporarily disrupt the gut microbiome is through the use of antibiotic therapies. Azithromycin is an antibiotic medicine prescribed to humans for the treatment of mild to moderate infections caused by bacteria. The purpose of the proposed project is to determine the influence of short-term (5-days) antibiotic therapy (azithromycin) on exercise performance in young, healthy adults. Treadmill exercise performance will be compared in two groups of adults before and after 5-days ingestion of azithromycin, or a placebo (something that has no physical effect).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used antibiotics or probiotics in the last 12 weeks.

What data supports the effectiveness of the drug Azithromycin?

Azithromycin has been shown to significantly reduce clinical failures in treating community-acquired pneumonia, preventing one clinical failure per 50 treated patients. However, it does not offer significant advantages for bronchitis compared to other antibiotics. ^{1 2 3 4 5}

Is Azithromycin generally safe for humans?

Azithromycin, also known as Zithromax or Zmax, is generally considered safe for humans and is commonly used to treat bacterial infections. However, like all medications, it can have side effects, including stomach upset, diarrhea, and allergic reactions. It is important to consult with a healthcare provider for personalized advice. ^{6 7 8 9 10}

How does the drug azithromycin affect exercise performance differently from other treatments?

Azithromycin is unique because it may trigger muscle damage (rhabdomyolysis) and exercise intolerance, especially when combined with physical activity and infection, unlike other treatments that do not typically have this effect. ^{11 12 13 14 15}

Research Team

Sara C Campbell, PhD

Principal Investigator

Rutgers, The State University of New Jersry

Christopher Bell, PhD

Principal Investigator

Colorado State University

Eligibility Criteria

This trial is for healthy adults aged 18-40 who exercise regularly (at least 150 minutes of moderate-to-vigorous activity per week) and can run on a treadmill for an hour. Women must use hormonal contraception. People with recent antibiotic or probiotic use, drug hypersensitivity, certain health conditions, or pregnancy are excluded.

Inclusion Criteria

Able and willing to run for 60 minutes on a treadmill without stopping

I identify as either male or female.

Completed a minimum of 150 minutes per week of moderate-to-vigorous physical activity over the previous year

Exclusion Criteria

I have a history of heart or blood vessel diseases, high blood pressure, stroke, heart murmur, sickle cell anemia, or lung problems.

I have taken antibiotics or probiotics in the last 3 months.

Currently pregnant, trying to become pregnant, or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Evaluation and Familiarization

Participants undergo baseline evaluation and familiarization with exercise protocols, including body composition assessment and VO2max testing.

1 week

2 visits (in-person)

Treatment

Participants receive 5 days of azithromycin or placebo, with exercise performance assessed before and after treatment.

5 days

2 visits (in-person)

Follow-up

Participants are monitored for changes in exercise performance, gut microbiota, and metabolomics after treatment.

1 week

1 visit (in-person)

Treatment Details

Interventions

• Azithromycin

Trial Overview The study tests the effect of a short-term course of Azithromycin, an antibiotic, on exercise performance in young adults. Participants will be randomly assigned to receive either Azithromycin or a placebo for five days and their treadmill performance will be compared before and after treatment.

Participant Groups

Group I: Antibiotics and exercise Experimental Treatment 1 Intervention

Participants will be tested before and after 5 days of azithromycin, per manufacturer's instructions, to determine if that impacts exercise performance and the gut microbiome and gut/serum metabolome.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Colorado State University

Collaborator

Trials

138

Recruited

38,200+

Findings from Research

In a study of 3,995 patients aged 2-94, azithromycin demonstrated a favorable safety profile, with only 12.0% of patients experiencing side effects, which is significantly lower than the 14.2% seen with other standard antibiotics.

The most common side effects were mild to moderate gastrointestinal issues, and only 0.7% of patients discontinued treatment due to side effects, indicating that azithromycin is well tolerated even among patients with various concurrent illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toleration and safety of azithromycin. Hopkins, S.[2022]

In a study of over 1 million episodes of azithromycin use among Danish adults, current use of azithromycin was linked to a significantly increased risk of cardiovascular death compared to no antibiotic use, with a rate ratio of 2.85.

However, when compared to penicillin V, another antibiotic, azithromycin did not show an increased risk of cardiovascular death, suggesting that its safety profile may be similar to that of penicillin in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of azithromycin and death from cardiovascular causes. Svanström, H., Pasternak, B., Hviid, A.[2022]

In a meta-analysis of randomized controlled trials involving 4,378 patients, azithromycin did not significantly reduce clinical failures in treating acute bronchitis and acute exacerbations of chronic bronchitis, indicating it may not be more effective than other antibiotics for these conditions.

However, azithromycin showed a significant reduction in clinical failures for community-acquired pneumonia, preventing approximately one clinical failure for every 50 patients treated, while maintaining a low discontinuation rate due to adverse events (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. Contopoulos-Ioannidis, DG., Ioannidis, JP., Chew, P., et al.[2019]

Azithromycin may be associated with QT prolongation and, in rare cases, can lead to serious heart rhythm issues like torsade de pointes, particularly in patients with existing cardiovascular risk factors.

In a study of 47 low-risk individuals, azithromycin treatment showed only a mild and statistically insignificant increase in QTc interval, suggesting that for patients without additional risk factors, azithromycin is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin-induced proarrhythmia and cardiovascular death. Howard, PA.[2022]

A systematic review of 5 cohort studies involving over 2.2 million episodes of azithromycin use found no overall increased risk of death from any cause, indicating that azithromycin is generally safe for most populations.

However, the analysis revealed that current use of azithromycin in older individuals (within 1-5 days of therapy) was associated with a higher risk of death, suggesting that alternative treatments may be advisable for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of Observational Studies. Bin Abdulhak, AA., Khan, AR., Garbati, MA., et al.[2018]

In a study involving 14 highly trained male athletes, the anti-leukotriene drug montelukast did not improve lung function or exercise performance compared to a placebo, indicating it may not enhance athletic performance in non-asthmatic individuals.

The results suggest that montelukast does not provide a performance advantage during high-intensity exercise, which supports the idea that asthmatic athletes can safely use this medication without gaining an unfair competitive edge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmatic endurance athletes. Sue-Chu, M., Sandsund, M., Holand, B., et al.[2021]

In a study involving 8 highly trained nonasthmatic cross-country skiers, inhaling 50 micrograms of salmeterol significantly improved lung function (FEV1) but did not enhance overall physical performance during exercise at -15 degrees C.

Despite the improvement in lung function, salmeterol did not affect key performance metrics such as heart rate, oxygen uptake, or running time to exhaustion, reinforcing its approval for use in asthmatic athletes rather than as a performance enhancer for healthy athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salmeterol and physical performance at -15 degrees C in highly trained nonasthmatic cross-country skiers. Sue-Chu, M., Sandsund, M., Helgerud, J., et al.[2015]

A meta-analysis of 8 controlled studies involving mice and monkeys found that moderate exercise (ME) significantly reduced morbidity during viral infections, suggesting it may help improve health outcomes during illness.

In contrast, exercising until fatigue (EF) showed a trend towards increased symptom severity and mortality, indicating that this type of exercise should be avoided during infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise effect on symptom severity, morbidity and mortality in viral infections: a systematic review and meta-analysis. de Araujo, RB., Chacon-Mikahil, MPT., Lord, JM., et al.[2022]

In a study involving patients with exercise-induced asthma, high-dose inhaled salmeterol (SX) provided greater pre-exercise bronchodilation compared to controlled release oral salbutamol (CR), indicating its superior efficacy in improving lung function before exercise.

Despite the increased baseline lung function with both treatments, neither SX nor CR showed significant improvements in cardiorespiratory performance during submaximal exercise, suggesting that short-term use of these bronchodilators does not enhance exercise capacity in individuals with exercise-induced asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cardiorespiratory response to submaximal exercise in subjects with asthma following pretreatment with controlled release oral salbutamol and high-dose inhaled salmeterol. Revill, SM., Morgan, MD.[2019]

Aerobic exercise significantly improves aerobic capacity, quality of life, and reduces depressive symptoms in people living with HIV on antiretroviral therapy, while resistance training enhances strength.

Combined aerobic and resistance training (CARET) leads to improvements in overall fitness, physical functioning, quality of life, and even positively affects CD4+ cell counts and HIV viral load, highlighting the potential of exercise as a therapeutic option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exercise training on disease progression, fitness, quality of life, and mental health in people living with HIV on antiretroviral therapy: a systematic review. Lopez, J., Richardson, E., Tiozzo, E., et al.[2022]

In a study involving patients treated with zidovudine (AZT), the recovery of phosphocreatine in calf muscles after exercise was significantly delayed compared to age-matched controls, indicating impaired mitochondrial function.

These results suggest that chronic AZT treatment may lead to mitochondrial myopathy due to its inhibitory effects on mitochondrial DNA synthesis and oxidative metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

31P magnetic resonance spectroscopy suggests impaired mitochondrial function in AZT-treated HIV-infected patients. Weissman, JD., Constantinitis, I., Hudgins, P., et al.[2019]

In a study involving male and female rats treated with zidovudine (ZDV) for 6 weeks, there were no significant differences in exercise performance or muscle tension output compared to control groups, suggesting that ZDV does not directly cause muscle contractile deficiencies.

Interestingly, ZDV-treated rats showed higher cytochrome oxidase activity in certain muscle fibers, indicating that the drug may not impair muscle function as previously thought, and that myopathies in AIDS patients could be more related to HIV infection complications rather than the drug itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of zidovudine (AZT) on the structure and function of rat skeletal muscle. Engbretson, BG.[2013]

A 17-year-old male developed severe muscle pain and elevated creatine kinase levels after taking azithromycin for a febrile infection, indicating a potential case of rhabdomyolysis.

The patient's symptoms improved rapidly after discontinuing azithromycin, suggesting that this antibiotic may have myotoxic effects, particularly in patients who are exercising or have infections, and should be used cautiously in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhabdomyolysis triggered by azithromycin. Finsterer, J., Stollberger, CC., Melichart-Kotig, M.[2022]

Patients on long-term zidovudine (AZT) therapy show significant muscle energy metabolism impairment, as evidenced by greater depletion of muscle phosphocreatine during exercise compared to both HIV-positive patients not treated with AZT and healthy controls.

The study, which involved 34 participants (19 normal volunteers, 6 untreated HIV-positive patients, and 9 AZT-treated patients), indicates that AZT treatment leads to decreased maximal work output and reduced muscle ATP synthesis, similar to effects seen in mitochondrial myopathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy. Sinnwell, TM., Sivakumar, K., Soueidan, S., et al.[2018]

In a study involving 15 highly trained male cyclists, the administration of 400 micrograms of salbutamol did not result in any significant improvements in cycling performance compared to a placebo.

The findings suggest that acute doses of salbutamol, even at twice the normal therapeutic level, do not enhance aerobic endurance or overall cycling performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of salbutamol on performance in endurance cyclists. Norris, SR., Petersen, SR., Jones, RL.[2020]

References

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

Clinical toleration and safety of azithromycin. [2022]

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

Use of azithromycin and death from cardiovascular causes. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. [2019]

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

Azithromycin-induced proarrhythmia and cardiovascular death. [2022]

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

Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of Observational Studies. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmatic endurance athletes. [2021]

7. Denmark pubmed.ncbi.nlm.nih.gov

Salmeterol and physical performance at -15 degrees C in highly trained nonasthmatic cross-country skiers. [2015]

8. Germany pubmed.ncbi.nlm.nih.gov

Exercise effect on symptom severity, morbidity and mortality in viral infections: a systematic review and meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The cardiorespiratory response to submaximal exercise in subjects with asthma following pretreatment with controlled release oral salbutamol and high-dose inhaled salmeterol. [2019]

10. Singapore pubmed.ncbi.nlm.nih.gov

The effect of exercise training on disease progression, fitness, quality of life, and mental health in people living with HIV on antiretroviral therapy: a systematic review. [2022]

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

31P magnetic resonance spectroscopy suggests impaired mitochondrial function in AZT-treated HIV-infected patients. [2019]

12. Canada pubmed.ncbi.nlm.nih.gov

Effect of zidovudine (AZT) on the structure and function of rat skeletal muscle. [2013]

13. India pubmed.ncbi.nlm.nih.gov

Rhabdomyolysis triggered by azithromycin. [2022]

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

Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy. [2018]

15. Germany pubmed.ncbi.nlm.nih.gov

The effect of salbutamol on performance in endurance cyclists. [2020]