Clinical trial NCT04789499: Smell in Covid-19 and Efficacy of Nasal Theophylline
Official title: Smell in Covid-19 and Efficacy of Nasal Theophylline
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Anosmia
Olfactory Disorder
Covid-19 Pandemic
SARS-CoV-2 Infection
Hyposmia
Ageusia
Hypogeusia
Keywords: Smell
Smell loss
smell dysfunction
olfactory dysfunction
COVID-19
anosmia
theophylline
nasal irrigation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2021-03-09
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: UPSIT
timeFrame: Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups
Secondary outcomes:
measure: University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: Comparison at 6 weeks post-intervention from baseline
measure: Change in Questionnaire for Olfactory Dysfunction (QOD) From Baseline to 6 Weeks Post Intervention
timeFrame: Comparison at 6 weeks post-intervention from baseline
measure: 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline assessment
measure: Olfactory Dysfunction Outcomes Rating (ODOR)
timeFrame: Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine in Saint Louis
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jay F Piccirillo, M.D., FACS
role: PRINCIPAL_INVESTIGATOR
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