Smell Changes & Efficacy of Nasal Theophylline (SCENT)

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

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.

Study Overview

• Status: Completed
• Conditions: Anosmia; Olfactory Disorder; Viral Infection; Smell Disorder; Theophylline Causing Adverse Effects in Therapeutic Use
• Intervention / Treatment: Drug: Theophylline; Drug: Saline Nasal

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Theophylline saline irrigation; 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; Theophylline delivered via high-volume, low-pressure nasal saline irrigation
Placebo Comparator: Placebo saline irrigation; 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; Lactose delivered via high-volume, low-pressure nasal saline irrigation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): January 15, 2021

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Adverse effects; Hyposmia; Smell; Theophylline; Olfactory dysfunction; Anosmia; Post-viral
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Infections; Neurologic Manifestations; Sensation Disorders; Disease; Virus Diseases; Anosmia; Olfaction Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Theophylline
• Other Study ID Numbers: 201901107

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No