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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the drug salsalate can reduce inflammation caused by vaping. Researchers aim to determine if vaping affects blood vessel function, which is crucial for heart health. Participants are divided into two groups: one group takes a placebo (a pill with no active ingredients) first, then switches to salsalate, while the other group does the opposite. The trial includes individuals aged 18 to 24 who have been vaping for at least six months or have never vaped. As an Early Phase 1 trial, this research seeks to understand how salsalate works in people, offering participants a chance to contribute to groundbreaking insights.

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.

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

Research has shown that salsalate is generally safe for use. Its long history in treating arthritis supports its safety profile. Some individuals might experience mild side effects, such as an upset stomach or ringing in the ears, when taking salsalate. These side effects are typically not serious and often resolve on their own. Although recent research on salsalate's safety for treating inflammation from vaping is lacking, its extensive use offers some confidence in its safety for potential trial participants.

New research may provide additional insights, so discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about salsalate for vaping-related inflammation because it offers a new approach compared to current treatments like corticosteroids or bronchodilators. Unlike these standard options that primarily address symptoms, salsalate is an anti-inflammatory drug that may target the inflammation at its root. Salsalate is derived from salicylic acid, similar to aspirin, and could potentially reduce inflammation without the side effects commonly associated with steroids. Additionally, its oral administration makes it convenient for users, possibly improving compliance and outcomes.

What evidence suggests that salsalate might be an effective treatment for vaping-related inflammation?

This trial will compare the effects of Salsalate and a placebo on vaping-related inflammation. Studies have shown that Salsalate reduces inflammation by slightly blocking an enzyme linked to it. Although Salsalate often treats arthritis, researchers are now investigating its potential to address inflammation from vaping. Early findings suggest that inflammation influences how vaping affects blood vessels. By reducing inflammation, Salsalate might improve blood vessel health in people who vape. However, further research is necessary to confirm its effectiveness for vaping-related issues. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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)

Use of stimulant drugs

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-electronic-cigarette-use-7-2024-5b122

Salsalate for Vaping-Related Inflammation What data supports the effectiveness of the drug Salsalate for vaping-related inflammation? Salsalate is a weak inhibitor of cyclooxygenase, which means it ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845662/

In vitro toxicological evaluation of aerosols generated by a ... Nicotine salts promote both inflammation and oxidative stress. The effect of nicotine salts was evaluated in comparison with freebase nicotine ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0300483X23002044

In Vitro high-throughput toxicological assessment of E ... We observed significant, dose-dependent adverse effects only with cinnamon, vanilla tobacco, and hazelnut e-liquids compared to media-only and PG/VG vehicle ...

4. ctv.veeva.com ctv.veeva.com/study/role-of-inflammation-in-vascular-phenotype-associated-with-e-cigarette-use

Role of Inflammation in Vascular Phenotype Associated with E ... While e-cigarettes have been marketed as a safer alternative to tobacco cigarettes, clinical studies examining these claims are limited.

5. pubs.acs.org pubs.acs.org/doi/10.1021/acs.chemrestox.4c00065

Quantification of Free Radicals from Vaping Electronic ... The acids in the nicotine salt formulations may alter the redox environment in e-cigarettes, impacting free radical formation in e-cigarette ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11332784/

Health outcomes of electronic cigarettes - PMC The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019.