Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)

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.

Inclusion criteria

• Participants will be recruited based on the following inclusion criteria:

• males and females ages 18 to 75 years
• located within or willing to travel to the state of Missouri or Illinois
• Olfactory dysfunction that has persisted for >3 months following suspected COVID-19 infection
• Baseline University of Pennsylvania Smell Identification Test (UPSIT) consistent with decreased olfactory function (<= 34 in women, <=33 in men). This test is a clinically validated 40-question forced-choice odor identification test where microencapsulated odorants on a strip are released by scratching.70 This will determine that patients have both subjectively and objectively diagnosed OD prior to undergoing treatment.
• Ability to read, write, and understand English and have access to email.

Exclusion criteria

• Individuals will not be allowed to participate in this study if they meet one or more of the following exclusion criteria:

• History of olfactory dysfunction prior to COVID-19 infection
• Any use of concomitant therapies specifically for the treatment of olfactory dysfunction
• Use of or participation in previous trials of intranasal theophylline.
• Known existence of nasal polyps, prior sinonasal, or anterior skull-based surgery
• Dependence on theophylline for comorbid conditions such as asthma and chronic obstructive pulmonary disease (COPD)
• History of an allergic reaction to theophylline or other methylxanthines
• 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.