Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)
NCT ID: NCT05947643
Last Updated: 2025-08-20
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
77 participants
Study Classification
INTERVENTIONAL
Study Start Date
2022-11-22
Study Completion Date
2025-08-04
Brief Summary
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The purpose of this Phase II trial is to test the effectiveness of intranasal theophylline irrigations for the treatment of COVID-19 related smell dysfunction. The investigators will compare the effect of theophylline nasal rinses versus placebo nasal rinses on smell symptoms. Participants will be asked to rinse their nose with a medication or placebo capsule dissolved in saltwater twice daily for 12 weeks and fill out surveys about smell before, during, and at the end of treatment.
This study will also be used to describe adverse effects related to intranasal theophylline irrigation.
This study will also be used to describe adverse effects related to intranasal theophylline irrigation.
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Detailed Description
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COVID-related olfactory dysfunction (OD) is a major symptom of infection with SARS-COV-2, affecting up to 80% of those with COVID-19. While research on the pathogenesis is ongoing, a significant subset is expected to suffer from long-term OD. The investigators seek to test intranasal theophylline nasal irrigation as a potential therapeutic option for treatment of COVID-related OD lasting over 3 months.
Theophylline has been shown to improve outcomes in post-viral OD in pilot studies, and initial data suggests therapeutic benefit in patients with post-COVID OD with minimal systemic absorption.
The primary hypothesis is that theophylline irrigation will be more effective than placebo saline irrigation for COVID-19 related OD symptoms. The use of intranasal theophylline will have minimal adverse effects.
Theophylline has been shown to improve outcomes in post-viral OD in pilot studies, and initial data suggests therapeutic benefit in patients with post-COVID OD with minimal systemic absorption.
The primary hypothesis is that theophylline irrigation will be more effective than placebo saline irrigation for COVID-19 related OD symptoms. The use of intranasal theophylline will have minimal adverse effects.
Conditions
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COVID-19
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
SINGLE_GROUP
Single-site, double-blinded, placebo-controlled randomized clinical trial performed at a tertiary academic medical center.
Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Participants
Investigators
Double-blinded, meaning neither the subjects nor the investigators will be aware of the intervention received by any subject.
Study Groups
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Theophylline
Participants will dissolve the contents of the 400 mg theophylline capsules (experimental) into the sinus rinse bottle containing nasal saline.
Group Type
EXPERIMENTAL
theophylline
Intervention Type
DRUG
capsules dissolved in intranasal irrigation
Placebo
Participant will dissolve the contents of the identical-appearing lactose capsules (control) into the sinus rinse bottle containing nasal saline.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
identical-appearing lactose capsules dissolved in intranasal irrigation
Interventions
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theophylline
capsules dissolved in intranasal irrigation
Intervention Type
DRUG
Placebo
identical-appearing lactose capsules dissolved in intranasal irrigation
Intervention Type
DRUG
Other Intervention Names
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inactive medicine
Eligibility Criteria
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Inclusion Criteria
1. males and females ages 18 to 75 years
2. located within or willing to travel to the state of Missouri or Illinois
3. Olfactory dysfunction that has persisted for \>3 months following suspected COVID-19 infection
4. Baseline University of Pennsylvania Smell Identification Test (UPSIT) consistent with decreased olfactory function (\<= 34 in women, \<=33 in men). This test is a clinically validated 40-question forced-choice odor identification test where microencapsulated odorants on a strip are released by scratching.70 This will determine that patients have both subjectively and objectively diagnosed OD prior to undergoing treatment.
5. Ability to read, write, and understand English and have access to email.
2. located within or willing to travel to the state of Missouri or Illinois
3. Olfactory dysfunction that has persisted for \>3 months following suspected COVID-19 infection
4. Baseline University of Pennsylvania Smell Identification Test (UPSIT) consistent with decreased olfactory function (\<= 34 in women, \<=33 in men). This test is a clinically validated 40-question forced-choice odor identification test where microencapsulated odorants on a strip are released by scratching.70 This will determine that patients have both subjectively and objectively diagnosed OD prior to undergoing treatment.
5. Ability to read, write, and understand English and have access to email.
Exclusion Criteria
1. History of olfactory dysfunction prior to COVID-19 infection
2. Any use of concomitant therapies specifically for the treatment of olfactory dysfunction
3. Use of or participation in previous trials of intranasal theophylline.
4. Known existence of nasal polyps, prior sinonasal, or anterior skull-based surgery
5. Dependence on theophylline for comorbid conditions such as asthma and chronic obstructive pulmonary disease (COPD)
6. History of an allergic reaction to theophylline or other methylxanthines
7. History of neurodegenerative disease (ie. Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia)
8. Pregnant or breastfeeding mothers.
9. Current use of medications with significant (≥40%) interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon- alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin.
2. Any use of concomitant therapies specifically for the treatment of olfactory dysfunction
3. Use of or participation in previous trials of intranasal theophylline.
4. Known existence of nasal polyps, prior sinonasal, or anterior skull-based surgery
5. Dependence on theophylline for comorbid conditions such as asthma and chronic obstructive pulmonary disease (COPD)
6. History of an allergic reaction to theophylline or other methylxanthines
7. History of neurodegenerative disease (ie. Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia)
8. Pregnant or breastfeeding mothers.
9. Current use of medications with significant (≥40%) interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon- alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin.
Minimum Eligible Age
18 Years
Maximum Eligible Age
75 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Washington University School of Medicine
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Jay F Piccirillo, MD
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
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Washington University School of Medicine
St Louis, Missouri, United States
Site Status
Countries
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United States
References
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Lee JJ, Peterson AM, Kallogjeri D, Jiramongkolchai P, Kukuljan S, Schneider JS, Klatt-Cromwell CN, Drescher AJ, Brunworth JD, Piccirillo JF. Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction. Am J Otolaryngol. 2022 Mar-Apr;43(2):103299. doi: 10.1016/j.amjoto.2021.103299. Epub 2021 Dec 3.
Reference Type
BACKGROUND
Lee JJ, Gupta S, Kallogjeri D, Piccirillo JF. Safety of High-Dose Nasal Theophylline Irrigation in the Treatment of Postviral Olfactory Dysfunction: A Dose-Escalation Study. JAMA Otolaryngol Head Neck Surg. 2022 Sep 1;148(9):885-886. doi: 10.1001/jamaoto.2022.1574.
Reference Type
BACKGROUND
Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984 Mar;32(3):489-502. doi: 10.1016/0031-9384(84)90269-5.
Reference Type
BACKGROUND
Theophylline in Dextrose [package insert]. Lake Forest, IL: Hospira, INC;2008
Reference Type
BACKGROUND
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
https://ClinicalTrials.gov/show/NCT04374474.
Anosmia Rehabilitation in Patients Post Coronavirus Disease (COVID 19).
https://ClinicalTrials.gov/show/NCT04495816.
COVID-19 Anosmia Study.
https://ClinicalTrials.gov/show/NCT04484493.
Corticosteroid Nasal Spray in COVID-19 Anosmia.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
202209062
Identifier Type: -
Identifier Source: org_study_id
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