Smell in Covid-19 and Efficacy of Nasal Theophylline
Condition: Covid19; Anosmia; Olfactory Disorder; Covid-19 Pandemic; SARS-CoV-2 Infection; Hyposmia; Ageusia; Hypogeusia
MeSH terms: COVID-19; Anosmia; Ageusia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Theophylline Powder; Placebo Comparator
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Theophylline nasal irrigation; lactose powder
Intervention MeSH terms: Theophylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Smell; Smell loss; smell dysfunction; olfactory dysfunction; COVID-19; anosmia; theophylline; nasal irrigation