Clinical trial NCT05947643: Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)
Official title: Smell in COVID-19 and Efficacy of Nasal Theophylline 3
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: COVID-19
Keywords: Nasal Theophylline
Olfactory disfunction
Anosmia
Gustatory disorders
Dysgeusia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2023-07-17
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Single-site, double-blinded, placebo-controlled randomized clinical trial performed at a tertiary academic medical center.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Global Impression Scale (CGI)
timeFrame: Week 6 and week 12 of treatment
Secondary outcomes:
measure: Olfactory Dysfunction Outcomes Rating (ODOR)
timeFrame: Week 6 and week 12 of treatment
measure: Assessment of adherence
timeFrame: Week 1-2 of treatment
measure: Assessment of blind
timeFrame: Week 1-2 of treatment
measure: Adverse effects
timeFrame: Patients may report this information any time during 12 weeks of treatment. They are asked about this at weeks 3, 6, 9, and 12 of treatment.
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jay F Piccirillo, MD
role: PRINCIPAL_INVESTIGATOR
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