Smell in Covid-19 and Efficacy of Nasal Theophylline

NCT04789499 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202101190
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• UPSIT

  UPSIT 0-40 with higher scores indicating better results. The response rate defined as the number of participants in each group self-reporting of at least slightly better improvement in the Clinical Global Improvement Scale at 6 weeks post intervention as compared to baseline, devided by the total number of participants in that specific group. The CGI-Improvement Scale has seven response options (from 1 as Very Much Improved to 7 as Very Much Worsened) for answers to the question "Compared to your sense of smell before you started the nasal irrigations, how would you rate your sense of smell now" . Participants reporting 3 as "Minimally Improved", 2 as "Much Improved", or 1 as "Very Much Improved" in the CGI-I will be deemed responders to treatment, and the rate of responders will be compared between the two arms.

  Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups

Secondary Outcomes (4)

• University of Pennsylvania Smell Identification Test (UPSIT)

  Comparison at 6 weeks post-intervention from baseline

• Change in Questionnaire for Olfactory Dysfunction (QOD) From Baseline to 6 Weeks Post Intervention

  Comparison at 6 weeks post-intervention from baseline

• 36-Item Short Form Health Survey (SF-36)

  Baseline assessment

• Olfactory Dysfunction Outcomes Rating (ODOR)

  Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups

Study Arms (2)

Theophylline

EXPERIMENTAL

400mg theophylline capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.

Drug: Theophylline Powder

Placebo

PLACEBO COMPARATOR

500mg lactose capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.

Drug: Placebo Comparator

Interventions

Theophylline Powder DRUG

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.

Also known as: Theophylline nasal irrigation

Theophylline

Placebo Comparator DRUG

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.

Also known as: lactose powder

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine in Saint Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (47)

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  PMID: 35797024 DERIVED

MeSH Terms

Conditions

COVID-19; Anosmia; Ageusia; Olfaction Disorders

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Taste Disorders

Results Point of Contact

• Title: Research Statistician
• Organization: Washington University in Saint Louis

kallogjerid@wustl.edu

3143621077

Study Officials

• Jay F Piccirillo, M.D., FACS

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The pharmacy will maintain the blind until the completion of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 9, 2021
• Study Start: March 15, 2021
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Locations

US (1)