Smell Changes & Efficacy of Nasal Theophylline

Phase 2

Completed

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

Interventions: Drug: Saline Nasal
Drug: Theophylline

Registration Number: NCT03990766

Lead Sponsor: Washington University School of Medicine

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo saline irrigation	Saline Nasal	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.
Theophylline saline irrigation	Theophylline	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Improvement in Global Rating of Smell Change	6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) Score Change	6 weeks	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.
Olfactory Dysfunction Outcomes Ratings (ODOR) Score Change	6 weeks	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.
University of Pennsylvania Smell Identification Test (UPSIT) Total Score Change	6 weeks	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.