Pseudoephedrine for Barotrauma

(HBOT Trial)

Overseen By Todd Kessinger, MD, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: John Muir Health

Must not be taking: Decongestants, Antihistamines, Nasal steroids

Disqualifiers: Pregnancy, Glaucoma, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pseudoephedrine, a common sinus relief drug, can prevent ear injuries during hyperbaric oxygen therapy (HBOT). HBOT treats various conditions but can sometimes cause pressure-related ear issues. Participants will receive either pseudoephedrine or a placebo (a dummy pill) to determine its effectiveness. The trial seeks new HBOT patients who can swallow pills and do not have specific health issues like heart disease or high blood pressure. As an unphased trial, it offers participants the opportunity to contribute to innovative research that could enhance HBOT safety.

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

The trial requires that you stop using decongestants, antihistamines, pseudoephedrine, nasal steroids, or oxymetazoline at least 12 hours before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pseudoephedrine is generally safe and well-tolerated. In previous studies, only a few participants reported side effects such as drowsiness. For example, one study found that seven participants felt drowsy after taking pseudoephedrine. This medicine is already approved to relieve nasal or sinus pain and pressure. While commonly used to treat congestion, researchers are studying its potential to prevent ear problems during activities like flying or diving. Overall, very few side effects have been observed, suggesting it is safe for most people when used as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Pseudoephedrine is unique because it targets barotrauma by reducing pressure in the Eustachian tubes, which can alleviate discomfort quickly. Unlike standard treatments like nasal decongestant sprays or antihistamines, pseudoephedrine is taken orally, which may provide a more convenient option for some individuals. Researchers are excited about pseudoephedrine's potential for rapid relief during activities like flying or diving, where barotrauma is common.

What evidence suggests that pseudoephedrine might be an effective treatment for barotrauma?

Research has shown that pseudoephedrine, which participants in this trial may receive, might help prevent ear problems caused by pressure changes, such as those experienced during flights or hyperbaric oxygen therapy (HBOT). Studies suggest that taking a 120 mg dose of pseudoephedrine at least 30 minutes before pressure changes can lower the risk of these ear issues. However, one study found it did not significantly reduce ear pain during flights. Overall, evidence indicates that pseudoephedrine could help prevent ear problems related to pressure changes, but results can vary. ^{1 2 5 6 7}

Who Is on the Research Team?

Jacinta Showers, RN

Principal Investigator

John Muir Health

Are You a Good Fit for This Trial?

This trial is for new patients aged 18-79 needing Hyperbaric Oxygen Therapy (HBOT), who speak English, can make decisions, and swallow a pill. It's not for those with high heart rate or blood pressure, prisoners, pregnant women, glaucoma or heart disease patients, allergy to pseudoephedrine or on MAOIs.

Inclusion Criteria

Fluent in English

I can swallow pills without any issues.

I am capable of making my own health decisions.

Exclusion Criteria

Prisoner

Intubated

Systolic Blood Pressure >160

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants take a pill (pseudoephedrine or placebo) before hyperbaric oxygen therapy and undergo ear examinations before and after therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Pseudoephedrine Pill

Trial Overview The study tests if pseudoephedrine prevents ear damage during HBOT compared to a placebo. Pseudoephedrine relieves nasal congestion but its effectiveness in preventing barotrauma during HBOT is being researched.

How Is the Trial Designed?

Group I: Pseudoephedrine Experimental Treatment 1 Intervention

over the counter pseudoephedrine

Group II: Placebo Placebo Group 1 Intervention

pharmacy created placebo capsule

Pseudoephedrine Pill is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sudafed for:

• Temporary relief of nasal or sinus pain and pressure
• Nasal congestion
• Sinus congestion
• Eustachian tube congestion
• Vasomotor rhinitis
• Allergic rhinitis
• Croup
• Sinusitis
• Otitis media
• Tracheobronchitis

Approved in European Union as Pseudoephedrine for:

• Nasal congestion
• Sinus congestion
• Eustachian tube congestion
• Vasomotor rhinitis
• Allergic rhinitis
• Croup
• Sinusitis
• Otitis media
• Tracheobronchitis

Approved in Canada as Pseudoephedrine for:

• Temporary relief of nasal or sinus pain and pressure
• Nasal congestion
• Sinus congestion
• Eustachian tube congestion

Who Is Running the Clinical Trial?

John Muir Health

Lead Sponsor

Trials

3

Recruited

550+

Published Research Related to This Trial

A single capsule of sustained release pseudoephedrine was found to be more effective than a placebo in relieving nasal congestion due to allergic rhinitis, based on both objective and subjective measurements.

The study reported no serious adverse reactions, indicating that pseudoephedrine is a safe option for treating nasal congestion, although it did not significantly affect other allergy symptoms like sneezing or itching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of sustained action pseudoephedrine in allergic rhinitis. Hamilton, LH., Chobanian, SL., Cato, A., et al.[2018]

In a study measuring the effects of 60 mg pseudoephedrine and pseudoephedrine-triprolidine taken four times a day for 5 days, neither medication showed any impairment in night vision, color perception, stereopsis, or reaction time.

These results suggest that both pseudoephedrine and pseudoephedrine-triprolidine are safe in terms of cognitive and visual performance when used as directed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pseudoephedrine and triprolidine on visual performance. Luria, SM., Paulson, HM., Ryan, AP., et al.[2013]

In a study involving 10 subjects, different formulations of L(+)pseudoephedrine showed significant differences in plasma concentrations and urinary excretion, with the immediate release formulation producing the highest peak plasma levels.

Despite variations in plasma concentration levels, the study found minimal significant effects on heart rate, blood pressure, or mental state ratings, indicating a good safety profile for the drug even with sustained use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of plasma levels of L(+) pseudoephedrine following different formulations, and their relation to cardiovascular and subjective effects in man. Bye, C., Hill, HM., Hughes, DT., et al.[2019]

In a study involving 412 children, Guaifenesin compound pseudoephedrine hydrochloride oral solution demonstrated significant efficacy in treating cough, nasal congestion, and runny nose, with an overall efficacy rate of 89.3%.

The treatment was well-tolerated, showing a low adverse event rate of only 0.92%, indicating it is a safe option for children suffering from symptoms related to common colds or acute tracheobronchitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution]. Lu, Q.[2016]

In a study of 131 males, pseudoephedrine treatment for nasal congestion was associated with a slight increase in voiding dysfunction scores, particularly in men aged 50 and older, indicating a potential risk even in patients without prior voiding issues.

The results suggest that older patients (≥50 years) may experience significant increases in urinary symptom scores after pseudoephedrine use, highlighting the need for caution when prescribing this medication to older males.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voiding dysfunction in patients with nasal congestion treated with pseudoephedrine: a prospective study. Shao, IH., Wu, CC., Tseng, HJ., et al.[2022]

Pseudoephedrine (PSE) is an effective medication for treating various respiratory conditions, including the common cold, flu, sinusitis, asthma, and bronchitis, due to its properties as a decongestant.

However, PSE is also misused for its stimulant effects, similar to amphetamines, leading to concerns about its potential for abuse and its role as a precursor in the illegal production of methamphetamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudoephedrine-Benefits and Risks. Głowacka, K., Wiela-Hojeńska, A.[2021]

In a study involving 318 children aged 6 to 11 years, ibuprofen (IBU) significantly reduced the number of wet nights in children with primary nocturnal enuresis (PNE) compared to placebo, while pseudoephedrine (PSE) alone did not show significant efficacy.

The combination of IBU and PSE did not enhance the effectiveness of IBU, and all treatments were well tolerated with no significant differences in adverse events among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled, exploratory trial of Ibuprofen and pseudoephedrine in the treatment of primary nocturnal enuresis in children. Gelotte, CK., Prior, MJ., Gu, J.[2013]

Oral pseudoephedrine leads to a small but significant increase in systolic blood pressure (SBP) by approximately 1 mm Hg and heart rate (HR) by about 2.8 beats per minute, based on a review of 24 trials involving 1285 patients.

The increase in blood pressure is more pronounced with higher doses and immediate-release formulations, while the effects are less significant in studies with a higher proportion of women and shorter treatment durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. Salerno, SM., Jackson, JL., Berbano, EP.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8198308/

Efficacy of pseudoephedrine for the prevention ... Our results suggest that use of an oral decongestant before flying decreases the incidence of middle ear barotrauma associated with ambient pressure changes ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0196064494703590

Efficacy of Pseudoephedrine for the Prevention ... These results suggest that treatment with 120 mg pseudoephedrine at least 30 minutes before flying appears to decrease the incidence of barotrauma. ...

3. uptodate.com uptodate.com/contents/ear-barotrauma/abstract/30

Medline ® Abstract for Reference 30 of 'Ear barotrauma' These results suggest that treatment with 120 mg pseudoephedrine at least 30 minutes before flying appears to decrease the incidence of barotrauma.

4. jamanetwork.com jamanetwork.com/journals/jamapediatrics/fullarticle/346876

Pseudoephedrine and Air Travel–Associated Ear Pain in ... Pseudoephedrine use was not associated with a decrease in ear pain during either ascent (4% with pseudoephedrine vs 5% with placebo; P ≈ 1.00) or descent (12% ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/11/NCT04332211/Prot_SAP_002.pdf

Pseudoephedrine Prophylaxis for Prevention of Middle Ear ... We used data from subjects provided pseudoephedrine less than 45 minutes before treatment only for estimates of the incidence of complications of HBO2 treatment ...

6. medcentral.com medcentral.com/drugs/monograph/4908-382619/pseudoephedrine-oral

Pseudoephedrine: uses, dosing, warnings, adverse events, ... Limited data indicate that pseudoephedrine may be more effective than placebo in preventing otitic barotrauma associated with underwater diving† .

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3931412/

A Case-Control Study of Hawaiian Scuba Divers Up to 65% of divers report this type of injury. In order to prevent barotrauma, many divers use a sympathomimetic decongestant drug such as pseudoephedrine ...