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

Trial Summary

What is the purpose of this trial?

The purpose of this research is to study whether the use of pseudoephedrine can help prevent middle ear trauma during HBOT. Pseudoephedrine is an approved drug that is used for temporary relief of nasal or sinus pain and pressure.

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.

What data supports the effectiveness of the drug pseudoephedrine for treating barotrauma?

Pseudoephedrine is known to help relieve nasal congestion, as shown in a study where it was more effective than a placebo for allergic rhinitis. It is also commonly used to treat symptoms of the common cold and flu, which may indirectly suggest its potential to alleviate pressure-related discomfort in barotrauma. ^{1 2 3 4 5}

Is pseudoephedrine generally safe for humans?

Pseudoephedrine is generally safe for humans, but it can cause some side effects like a small increase in blood pressure and heart rate. It may also cause voiding dysfunction (difficulty urinating) in some people, but serious adverse reactions are rare. ^{1 5 6 7 8}

How does the drug pseudoephedrine differ from other treatments for barotrauma?

Pseudoephedrine is unique because it is primarily used as a nasal decongestant and has stimulant properties, which may help relieve pressure-related discomfort in barotrauma by reducing nasal congestion and improving airflow. Unlike other treatments, it is taken orally and can have effects on heart rate and sleep, which may not be common with other barotrauma treatments. ^{1 2 3 4 7}

Research Team

Jacinta Showers, RN

Principal Investigator

John Muir Health

Eligibility Criteria

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

I am between 18 and 79 years old.

I can swallow pills without any issues.

Fluent in English

Exclusion Criteria

Prisoner

Intubated

Systolic Blood Pressure >160

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

References

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

Effects of pseudoephedrine and triprolidine on visual performance. [2013]

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

A randomized, placebo-controlled, exploratory trial of Ibuprofen and pseudoephedrine in the treatment of primary nocturnal enuresis in children. [2013]

3. Germany 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. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pseudoephedrine-Benefits and Risks. [2021]

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

A study of sustained action pseudoephedrine in allergic rhinitis. [2018]

6. China pubmed.ncbi.nlm.nih.gov

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

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

Voiding dysfunction in patients with nasal congestion treated with pseudoephedrine: a prospective study. [2022]

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

Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis. [2013]