Smell in Covid-19 and Efficacy of Nasal Theophylline

Purpose

Evidence of COVID-19 related anosmia and dysgeusia continues to accumulate daily. Currently, up to 80% of patients report subjective olfactory dysfunction (OD), and prevalence using objective olfactory testing could be even higher. We propose a phase II single-site, double-blinded, placebo-controlled randomized clinical trial to determine the efficacy and safety of intranasal theophylline, a known phosphodiesterase inhibitor in the treatment of asthma, as a possible treatment for COVID-19 related OD. Theophylline has shown benefit in similar clinical trials for post-viral OD.

Conditions

  • Covid19
  • Anosmia
  • Olfactory Disorder
  • Covid-19 Pandemic
  • SARS-CoV-2 Infection
  • Hyposmia
  • Ageusia
  • Hypogeusia

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Olfactory dysfunction that has persisted for >3 months following suspected COVID-19 infection - Residing within the states of Missouri or Illinois. - Can read, write, and understand English.

Exclusion Criteria

  • History of olfactory dysfunction prior to COVID-19 infection - Use of concomitant therapies specifically for the treatment of olfactory dysfunction - History of olfactory dysfunction longer than 12 months - Known existence of nasal polyps, prior sinonasal, or anterior skull-based surgery - Dependence on theophylline for comorbid conditions such as asthma and 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 interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon-alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin. - Pre-existing arrhythmias or seizures

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
The pharmacy will maintain the blind until the completion of the study.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Theophylline 		400mg theophylline capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.
  • Drug: Theophylline Powder
    Twice daily nasal irrigation with 400 mg theophylline capsules and USP Grade Sodium Chloride & Sodium Bicarbonate Mixture (pH balanced, Isotonic & Preservative & Iodine Free) commercially prepared packets dissolved in 240 ml of distilled water.
    Other names:
    • Theophylline nasal irrigation
Placebo Comparator
Placebo 		500mg lactose capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.
  • Drug: Placebo Comparator
    Twice daily nasal irrigation with 500 mg lactose powder capsules and USP Grade Sodium Chloride & Sodium Bicarbonate Mixture (pH balanced, Isotonic & Preservative & Iodine Free) commercially prepared packets dissolved in 240 ml of distilled water.
    Other names:
    • lactose powder

Recruiting Locations

More Details

NCT ID
NCT04789499
Status
Completed
Sponsor
Washington University School of Medicine

Detailed Description

Post-viral olfactory dysfunction has numerous known adverse effects such as loss of cortical gray matter and decrease in quality of life. COVID-19 related olfactory dysfunction has already been shown to be correlated with depression and decreased quality of life, so finding an effective treatment is imperative. Intranasal and oral corticosteroids as well as olfactory training are currently used to treat post-viral OD; however they have demonstrated limited efficacy and there is no current gold standard of care. There is no current consensus on the pathogenesis of COVID-related anosmia; however evidence for post-viral olfactory dysfunction suggests sensory axonal regeneration and olfactory signaling may rely on elevated levels of secondary messengers cAMP and cGMP, a known effect of theophylline. In this phase II treatment trial, patients will be allocated 1:1 to receive either intranasal theophylline irrigation or placebo for six weeks. Various smell surveys and scratch-and-sniff tests will be utilized to capture changes in smell ability. Due to COVID-19, this study will be conducted virtually, except for the first ten enrolled patients who will undergo one serum theophylline test. This study is limited to patients living in Missouri or Illinois.