Salsalate for Vaping-Related Inflammation

Recruiting at 1 trial location

Overseen By Anna Stanhewicz, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Iowa

Must not be taking: Statins, Antihypertensives, Stimulants, others

Disqualifiers: Tobacco use, Skin diseases, CVD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not take statins, other cholesterol-lowering medications, or antihypertensive medications. If you are on these medications, you would need to stop taking them to participate.

What data supports the effectiveness of the drug Salsalate for vaping-related inflammation?

Salsalate is a weak inhibitor of cyclooxygenase, which means it may cause fewer respiratory reactions compared to aspirin in aspirin-sensitive patients with asthma. This suggests it might be less likely to cause inflammation-related issues in similar conditions. ^{1 2 3 4 5}

How does the drug Salsalate differ from other treatments for vaping-related inflammation?

Salsalate is unique because it is an anti-inflammatory drug traditionally used for conditions like arthritis, and it may help address the underlying inflammation caused by vaping, unlike other treatments that primarily focus on symptom relief. ^{6 7 8 9 10}

What is the purpose of this trial?

The use of electronic nicotine delivery systems, or e-cigarettes - colloquially referred to as "vaping" - in the United States has increased exponentially since their introduction to the US market in 2007. Prevalence of ever and current e-cigarette use is highest among teenagers and young adults with 16-28% of this population having reported vaping. While the majority of e-cigarette users are current tobacco smokers, 32.5% of current e-cigarette users are never- or former-smokers, representing a growing population of young adults who exclusively vape. While e-cigarettes have been marketed as a safer alternative to tobacco cigarettes, clinical studies examining these claims are limited. Cardiovascular disease (CVD) is the primary cause of premature death among tobacco cigarette smokers and reductions in vascular endothelial function, a significant predictor of future CVD, are detectible in otherwise healthy young adults who smoke. Despite the explosion in e-cigarette use among young adults, the health effects - especially the effects on mechanisms of vascular function - of these devices remain relatively unexplored. The purpose of this study is to directly asses the mechanistic role of inflammation in this dysfunction.

Eligibility Criteria

This trial is for young adults who currently use e-cigarettes ('vape'). Participants should not be tobacco smokers and must have no history of cardiovascular disease. The study aims to understand the impact of vaping on blood vessel function and inflammation.

Inclusion Criteria

I have never used e-cigarettes OR I have been using e-cigarettes for 6 months or more.

Exclusion Criteria

I have or might have liver disease or diabetes.

Tobacco cigarette use (current or history of)

Allergy to materials used during the experiment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or salsalate treatment for 4 days, followed by a 14-day washout period, then switch treatments for another 4 days

4 weeks

2 visits (in-person) for experimental testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Salsalate

Trial Overview The trial is testing whether Salsalate, an anti-inflammatory medication, can improve blood vessel function in vapers compared to a placebo (a pill with no active drug). It's designed to see if reducing inflammation benefits vascular health in e-cigarette users.

Participant Groups

Group I: Salsalate then Placebo Experimental Treatment 2 Interventions

Salsalate oral tablet 1500mg twice daily for 4 days prior to experimental testing followed by 14 day washout period and then placebo oral tablet twice daily for 4 days prior to experimental testing.

Group II: Placebo then Salsalate Experimental Treatment 2 Interventions

Placebo oral table twice daily for 4 days prior to experimental testing followed by 14 day washout period and then salsalate oral tablet 1500mg twice daily for 4 days prior to experimental testing.

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Findings from Research

In a study of 10 aspirin-sensitive asthma patients, only 2 experienced respiratory reactions to salsalate, indicating that salsalate is generally safer than aspirin for these individuals.

Salsalate may occasionally cause mild asthmatic reactions in aspirin-sensitive patients, but these reactions can be effectively managed with beta 2-agonists, suggesting a lower risk profile compared to aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. Stevenson, DD., Hougham, AJ., Schrank, PJ., et al.[2019]

Aspirin-sensitive asthma is characterized by severe eosinophilic inflammation and is more common in non-atopic, middle-aged women with chronic rhino-sinusitis and nasal polyps, highlighting the need for careful diagnosis and management.

Avoiding aspirin and NSAIDs is essential to prevent serious reactions, and treatment typically involves corticosteroids and possibly anti-leukotriene agents, with aspirin desensitization showing potential benefits for nasal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin-sensitive asthma: recent advances in management. Park, HS.[2018]

Antileukotrienes, such as montelukast and zileuton, are effective anti-inflammatory medications for asthma, showing significant improvements in patient-reported symptoms and quality of life compared to placebo, although their impact on objective lung function measures is less pronounced.

While generally well tolerated, antileukotrienes can have side effects, including potential liver enzyme elevations with zileuton and a rare association with Churg-Strauss syndrome, but the overall benefits of these medications in asthma management outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk assessment of antileukotrienes in the management of asthma. García-Marcos, L., Schuster, A., Pérez-Yarza, EG.[2018]

In patients with aspirin-intolerant asthma (AIA), significant changes in DNA methylation were observed in nasal polyps, with hypermethylation at 332 loci and hypomethylation at 158 loci, affecting 337 genes overall.

The study identified specific genes and pathways related to immune responses and inflammation that are altered in AIA, suggesting potential targets for future research into the mechanisms of aspirin hypersensitivity in asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics. Cheong, HS., Park, SM., Kim, MO., et al.[2022]

NSAID-exacerbated asthma can affect children as well as adults, with up to 2% of asthmatic children and nearly 30% of older children with severe asthma experiencing reactions, highlighting the need for caution in prescribing NSAIDs to this population.

The use of non-selective NSAIDs like ibuprofen should be avoided in teenagers and adults with known sensitivities, while alternatives like paracetamol, opioids, or tramadol may be safer options for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A teenager with severe asthma exacerbation following ibuprofen. Palmer, GM.[2019]

The metered dose inhaler (CBD-MDI) formulation of cannabidiol (CBD) was found to be safe for respiratory cells and did not provoke an immune response in alveolar macrophages, indicating its potential for therapeutic use.

CBD-MDI effectively reduced inflammation caused by various stimuli, including viral and bacterial antigens, and showed comparable efficacy to the corticosteroid budesonide, suggesting it may be a viable treatment option for inflammation rather than a preventive measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants. Srichana, T., Chunhachaichana, C., Suedee, R., et al.[2022]

Roflumilast, a selective phosphodiesterase 4 inhibitor, significantly improved lung function (measured by FEV1) in patients with severe COPD compared to placebo, despite the increases being small.

In addition to improving lung function, roflumilast reduced the rate of COPD exacerbations by 17% over placebo, and it was well-tolerated, with a similar rate of serious adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast: in chronic obstructive pulmonary disease. Sanford, M.[2021]

Roflumilast, a phosphodiesterase-4 inhibitor, has shown potential as an effective anti-inflammatory treatment for asthma and COPD, based on various studies including animal and human trials.

The drug has a favorable safety profile with no documented drug interactions, making it a promising option for patients, although further research is necessary to confirm its role in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. Karish, SB., Gagnon, JM.[2022]

In a study involving 31 patients with asthma (16 non-smokers and 15 smokers), the combination of fluticasone and salmeterol (FP/SM) significantly improved airway hyperresponsiveness in smokers, while doubling the dose of fluticasone alone did not provide the same benefit.

The results suggest that salmeterol's smooth muscle stabilization is particularly important for smokers with asthma, as it led to greater improvements in airway function compared to increasing fluticasone dosage, highlighting the need for tailored treatments in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone/Salmeterol combination confers benefits in people with asthma who smoke. Clearie, KL., McKinlay, L., Williamson, PA., et al.[2017]

The STIFLE study will investigate the effects of as-needed budesonide/formoterol on airway inflammation and asthma symptoms in 60-80 adult patients over 24 weeks, comparing it to salbutamol, a traditional reliever medication.

This research aims to provide mechanistic insights into how budesonide/formoterol not only alleviates symptoms but also addresses underlying inflammation, potentially reducing the risk of severe asthma exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design. Harrison, T., Pavord, ID., Chalmers, JD., et al.[2020]

References

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

Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. [2019]

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

Aspirin-sensitive asthma: recent advances in management. [2018]

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

Benefit-risk assessment of antileukotrienes in the management of asthma. [2018]

4. Denmark pubmed.ncbi.nlm.nih.gov

Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics. [2022]

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

A teenager with severe asthma exacerbation following ibuprofen. [2019]

6. France pubmed.ncbi.nlm.nih.gov

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants. [2022]

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

Roflumilast: in chronic obstructive pulmonary disease. [2021]

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

The potential role of roflumilast: the new phosphodiesterase-4 inhibitor. [2022]

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

Fluticasone/Salmeterol combination confers benefits in people with asthma who smoke. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design. [2020]