Smell Changes & Efficacy of Nasal Theophylline

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of nasal theophylline irrigation in treating smell loss related to a viral respiratory infection. Half the participants will undergo nasal theophylline irrigation treatment while the other half will undergo placebo nasal irrigation with saline alone. All participants will have their sense of smell tested before and after 6 weeks of treatment. All participants will also be regularly asked about any potential side effects related to treatment. In addition, the first 10 participants will have their blood drawn to measure their theophylline level after 1 week of starting treatment to ensure it is not abnormally elevated.

Official Title
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SCENT Trial: Nasal Theophylline Irrigation for Treatment of Post-Viral Olfactory Dysfunction

Conditions
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Anosmia, Olfactory Disorder, Viral Infection, Theophylline Causing Adverse Effects in Therapeutic Use, Smell Disorder

Intervention / Treatment
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* Drug: Theophylline
* Drug: Saline Nasal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjective or clinically diagnosed olfactory dysfunction of 6 months to 36 months duration after a presumed viral upper respiratory infection Ability to read, write, and understand English Exclusion Criteria: Dependence on theophylline for comorbid conditions such as asthma and chronic obstructive pulmonary disease History of an allergic reaction to theophylline or other methylxanthines Prior sinonasal or anterior skull base surgery Nasal polyposis History of neurodegenerative disease (ie. Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia) Pregnant or breastfeeding mothers Current use of medications with significant (≥40%) interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon-alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two randomized arms
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theophylline saline irrigation<br>Theophylline 12 mg capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride & Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily. | Drug: Theophylline<br>* Theophylline delivered via high-volume, low-pressure nasal saline irrigation<br>|
| Placebo Comparator: Placebo saline irrigation<br>Identical-appearing lactose monohydrate capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride & Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily. | Drug: Saline Nasal<br>* Lactose delivered via high-volume, low-pressure nasal saline irrigation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Improvement in Global Rating of Smell Change | Self-reported change in smell after intervention on a 7-point Likert scale. Response options with corresponding point values: 7) Much better, 6) Somewhat better, 5) Slightly better, 4) Neither better nor worse, 3) Slightly worse, 2) Somewhat worse, and 1) Much worse. The maximum score is 7, and higher values indicate better outcomes. A score of 4 is considered neutral. Scores of 5 or higher indicated clinical improvement. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| University of Pennsylvania Smell Identification Test (UPSIT) Total Score Change | Within- and between-subject changes in UPSIT total scores measured at baseline and at 6 weeks after therapy. This test is a validated 40-question forced-choice odor identification test where microencapsulated odorants on a strip are released by scratching. Each question corresponds to one point, and there are no subscales. The minimum score is 0 while the maximum score is 40, and higher values indicate better outcomes. | 6 weeks | 
| Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) Score Change | Within- and between-subject changes in QOD-NS scores measured at baseline and at 6 weeks after therapy, which is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. Each question is scored from 0 to 3 points, and there are no subscales. The minimum score is 0 while the maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment. | 6 weeks | 
| Olfactory Dysfunction Outcomes Ratings (ODOR) Score Change | Within- and between-subject changes measured at baseline and at 6 weeks after therapy. This test is a new disease-specific 28-item questionnaire that assesses for physical, functional, and emotional limitations in patients with olfactory dysfunction of any etiology. Each question is scored from 0 to 4. The minimum score is 0 while the maximum score is 112, and higher values indicate higher degree of limitations and worse outcomes. There are no subscales within the current questionnaire. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Olfactory dysfunction, Anosmia, Hyposmia, Post-viral, Theophylline, Adverse effects, Smell