The purpose of this Phase II trial is to test the effectiveness of intranasaltheophylline irrigations for the treatment of COVID-19 related smell dysfunction. Theinvestigators will compare the effect of theophylline nasal rinses versus placebo nasalrinses on smell symptoms. Participants will be asked to rinse their nose with amedication or placebo capsule dissolved in saltwater twice daily for 12 weeks and fillout surveys about smell before, during, and at the end of treatment.This study will also be used to describe adverse effects related to intranasaltheophylline 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.
Drug: theophylline
capsules dissolved in intranasal irrigation
Drug: Placebo
identical-appearing lactose capsules dissolved in intranasal irrigation
Other Name: inactive medicine
Inclusion Criteria:
- Participants will be recruited based on the following inclusion criteria:
1. males and females ages 18 to 75 years
2. located within or willing to travel to the state of Missouri or Illinois
3. Olfactory dysfunction that has persisted for >3 months following suspected
COVID-19 infection
4. 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.
5. 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:
1. History of olfactory dysfunction prior to COVID-19 infection
2. Any use of concomitant therapies specifically for the treatment of olfactory
dysfunction
3. Use of or participation in previous trials of intranasal theophylline.
4. Known existence of nasal polyps, prior sinonasal, or anterior skull-based
surgery
5. Dependence on theophylline for comorbid conditions such as asthma and chronic
obstructive pulmonary disease (COPD)
6. History of an allergic reaction to theophylline or other methylxanthines
7. History of neurodegenerative disease (ie. Alzheimer's dementia, Parkinson's
disease, Lewy body dementia, frontotemporal dementia)
8. Pregnant or breastfeeding mothers.
9. 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.
Washington University School of Medicine
Saint Louis, Missouri, United States
Jay F Piccirillo, MD, Principal Investigator
Washington University School of Medicine