Smell in Covid-19 and Efficacy of Nasal Theophylline (SCENT2)

The Washington University

Status and phase

Completed

Phase 2

Conditions

Anosmia

SARS-CoV-2 Infection

Covid-19 Pandemic

Hyposmia

Hypogeusia

Covid19

Olfactory Disorder

Ageusia

Treatments

Drug: Theophylline Powder

Drug: Placebo Comparator

Study type

Interventional

Funder types

Other

Identifiers

NCT04789499

202101190

Details and patient eligibility

About

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.

Full 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.

Enrollment

51 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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