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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how a short course of the antibiotic azithromycin affects exercise performance in young, healthy adults. It examines whether disrupting the gut microbiome (the community of bacteria in the stomach and intestines) influences muscle function during exercise. Participants will run on a treadmill before and after taking either azithromycin or a placebo for five days. Individuals who have been physically active for at least 150 minutes per week over the past year and can run for an hour without stopping might be suitable for this study. As an Early Phase 1 trial, this research seeks to understand azithromycin's impact on exercise performance, offering participants a unique opportunity to contribute to groundbreaking scientific knowledge.

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.

Is there any evidence suggesting that azithromycin is likely to be safe for humans?

Research has shown that azithromycin is generally safe for adults. This antibiotic often treats mild to moderate bacterial infections. In one study involving 728 adults who took a single dose of azithromycin, most did not experience serious side effects. Some individuals reported minor issues like an upset stomach or diarrhea.

However, there is a rare but serious risk related to the heart. Azithromycin can sometimes cause changes in heart rhythm, which could be dangerous. Although uncommon, this risk is important to be aware of. Overall, many people have used azithromycin safely, but being informed about possible risks is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for enhancing exercise performance focus on physical training and nutritional supplements. But Azithromycin works differently, as it is an antibiotic that researchers believe might impact exercise performance by altering the gut microbiome and metabolome. Unlike conventional methods that rely on prolonged periods to show results, Azithromycin has the potential to demonstrate its effects in just five days. This quick action and its novel approach to potentially boosting exercise performance by targeting gut health make it an intriguing option for researchers.

What evidence suggests that azithromycin might be an effective treatment for improving exercise performance?

Research has shown that azithromycin is an antibiotic that stops bacteria from making the proteins they need to grow. This might alter the bacteria in the stomach and intestines, potentially affecting muscle function and exercise performance. However, no direct evidence in humans shows that azithromycin improves exercise performance. In fact, some studies suggest that azithromycin might cause muscle problems, such as rhabdomyolysis, a serious condition where muscle tissue breaks down. This trial will test the impact of azithromycin on exercise performance and the gut microbiome in humans. So far, the positive effects observed in animal studies have not been proven in humans. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Bell, PhD

Principal Investigator

Colorado State University

Sara C Campbell, PhD

Principal Investigator

Rutgers, The State University of New Jersry

Are You a Good Fit for This Trial?

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

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

I identify as either male or female.

Exclusion Criteria

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

Currently pregnant, trying to become pregnant, or breastfeeding

Identification of a contraindication to exercise

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-gastrointestinal-microbiome-8-2023-a61d2

Azithromycin Impact on Exercise Performance 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9254748/

Rhabdomyolysis triggered by azithromycin - PMC Azithromycin may trigger rhabdomyolysis in the context of exercise and infection. Azithromycin may be myotoxic and should be prescribed with caution.

3. ctv.veeva.com ctv.veeva.com/study/influence-of-short-term-antibiotic-therapy-on-exercise

Influence of Short-Term Antibiotic Therapy on Exercise Treadmill exercise performance will be compared in two groups of adults before and after 5-days ingestion of azithromycin, or a placebo ( ...

4. singlecare.com singlecare.com/blog/working-out-on-antibiotics/

Is it safe to work out when you're taking antibiotics? The short answer is, generally, yes: Most antibiotics are safe to take while engaging in normal exercise, given that you're otherwise healthy and feel well ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163725814000552

Azithromycin: Mechanisms of action and their relevance for ... Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm.

6. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-azithromycin-zithromax-or-zmax-and-risk-potentially-fatal-heart

Azithromycin (Zithromax or Zmax) and the risk of potentially ... Azithromycin (Zithromax or Zmax) can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/050797s026lbl.pdf

Zmax (Azithromycin) Label - accessdata.fda.gov Adults: The data described below reflect exposure to Zmax in 728 adult patients. All patients received a single. 2 g oral dose of Zmax. The population studied ...

8. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=15258

ZITHROMAX® - (Azithromycin) There are no data concerning the possibility of an interaction between ergot and azithromycin.

9. drugs.com drugs.com/pro/zmax.html

Zmax: Package Insert / Prescribing Information Zmax is a macrolide antimicrobial drug indicated for mild to moderate infections caused by designated, susceptible bacteria.

10. rxlist.com rxlist.com/zmax-drug.htm

Zmax (Azithromycin): Side Effects, Uses, Dosage ... The data described below reflect exposure to Zmax in 728 adult patients. All patients received a single 2 g oral dose of Zmax. The population studied had ...