The purpose of this Phase II trial is to test the effectiveness of intranasal theophylline irrigations for the treatment of COVID-19 related smell dysfunction. The investigators will compare the effect of theophylline nasal rinses versus placebo nasal rinses on smell symptoms. Participants will be asked to rinse their nose with a medication or placebo capsule dissolved in saltwater twice daily for 12 weeks and fill out surveys about smell before, during, and at the end of treatment. This study will also be used to describe adverse effects related to intranasal theophylline irrigation.
COVID-related olfactory dysfunction (OD) is a major symptom of infection with SARS-COV-2, affecting up to 80% of those with COVID-19. While research on the pathogenesis is ongoing, a significant subset is expected to suffer from long-term OD. The investigators seek to test intranasal theophylline nasal irrigation as a potential therapeutic option for treatment of COVID-related OD lasting over 3 months. Theophylline has been shown to improve outcomes in post-viral OD in pilot studies, and initial data suggests therapeutic benefit in patients with post-COVID OD with minimal systemic absorption. The primary hypothesis is that theophylline irrigation will be more effective than placebo saline irrigation for COVID-19 related OD symptoms. The use of intranasal theophylline will have minimal adverse effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
77
capsules dissolved in intranasal irrigation
identical-appearing lactose capsules dissolved in intranasal irrigation
Washington University School of Medicine
St Louis, Missouri, United States
Clinical Global Impression - Improvement Scale
The Clinical Global Impression-Improvement scale (CGI-I) is a subjective rating scale used to measure changes in a patient's condition over time. It ranges from 1 to 7, where 1 means "Very Much Improved," 2 means "Much Improved," 3 means "Minimally Improved," 4 means "No Change," 5 means "Minimally Worse," 6 means "Much Worse," and 7 means "Very Much Worsened." In this study, participants reporting scores of 1, 2, or 3 on the CGI-I are considered responders to treatment. The primary analysis will compare the proportion of responders between the theophylline and placebo groups assessing both within-subject changes over time and between-group differences. We will measure the response rate defined as the number of participants self-reporting minimal change or larger in the Clinical Global Impression Scale (CGI) scale, divided by the number of participants in each group.The main comparison will be focused on changes at 12-weeks
Time frame: week 12
Olfactory Dysfunction Outcomes Rating
Olfactory Dysfunction Outcomes Rating (ODOR) is a disease-specific questionnaire that assesses for physical, functional, and emotional limitations in participants with olfactory dysfunction of any etiology. The instrument contains 28 total items with each scored on a 5-point Likert scale from 0 to 4. Total score ranges from 0 to 112. Higher scores indicate higher degree of dysfunction and limitation.
Time frame: 6 weeks and 12 week
Assessment of Adherence
Participants will be contacted to report the number of irrigations completed over the prior 7 days out of a possible 14. Participants report their compliance with the twice-daily nasal irrigations through self-reported measures in REDCap surveys, including how many rinses they have completed. The measure count represents the self-reported compliance with twice daily irrigations.
Time frame: 12 weeks
Assessment of Blind
The assessment of the blind in this study involves contacting participants within the first 3 weeks after starting nasal irrigations and asking them which treatment arm they believe they were assigned to-either "theophylline and nasal saline irrigation" or "nasal saline irrigation alone." The numbers reported represent how many participants correctly guessed an arm in which they were assigned to.
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Time frame: within first 3 weeks
Adverse Effects
Patients will be asked to report any adverse effects they experience at any time during the 12-week study period. An adverse event in this study refers to any undesirable or unintended medical occurrence experienced by a participant during the trial, which may or may not be related to the use of intranasal theophylline.
Time frame: up to 12 weeks