Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)

August 18, 2025 updated by: Washington University School of Medicine

Smell in COVID-19 and Efficacy of Nasal Theophylline 3

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
77

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants will be recruited based on the following 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.

Exclusion Criteria:

  • Individuals will not be allowed to participate in this study if they meet one or more of the following 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Theophylline
Participants will dissolve the contents of the 400 mg theophylline capsules (experimental) into the sinus rinse bottle containing nasal saline.
Drug: theophylline
capsules dissolved in intranasal irrigation
Placebo Comparator: Placebo
Participant will dissolve the contents of the identical-appearing lactose capsules (control) into the sinus rinse bottle containing nasal saline.
Drug: Placebo
identical-appearing lactose capsules dissolved in intranasal irrigation
Other Names:
  • inactive medicine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Clinical Global Impression - Improvement Scale
Time Frame: week 12

The Clinical Global Impression-Improvement scale (CGI-I) is a subjective rating scale used to measure changes in a patient's condition over time. It ranges from 1 to 7, where 1 means "Very Much Improved," 2 means "Much Improved," 3 means "Minimally Improved," 4 means "No Change," 5 means "Minimally Worse," 6 means "Much Worse," and 7 means "Very Much Worsened." In this study, participants reporting scores of 1, 2, or 3 on the CGI-I are considered responders to treatment. The primary analysis will compare the proportion of responders between the theophylline and placebo groups assessing both within-subject changes over time and between-group differences.

We will measure the response rate defined as the number of participants self-reporting minimal change or larger in the Clinical Global Impression Scale (CGI) scale, divided by the number of participants in each group.The main comparison will be focused on changes at 12-weeks
week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Olfactory Dysfunction Outcomes Rating
Time Frame: 6 weeks and 12 week

Olfactory Dysfunction Outcomes Rating (ODOR) is a disease-specific questionnaire that assesses for physical, functional, and emotional limitations in participants with olfactory dysfunction of any etiology. The instrument contains 28 total items with each scored on a 5-point Likert scale from 0 to 4.

Total score ranges from 0 to 112. Higher scores indicate higher degree of dysfunction and limitation.
6 weeks and 12 week
Assessment of Adherence
Time Frame: 12 weeks

Participants will be contacted to report the number of irrigations completed over the prior 7 days out of a possible 14.

Participants report their compliance with the twice-daily nasal irrigations through self-reported measures in REDCap surveys, including how many rinses they have completed.

The measure count represents the self-reported compliance with twice daily irrigations.
12 weeks
Assessment of Blind
Time Frame: within first 3 weeks

The assessment of the blind in this study involves contacting participants within the first 3 weeks after starting nasal irrigations and asking them which treatment arm they believe they were assigned to-either "theophylline and nasal saline irrigation" or "nasal saline irrigation alone."

The numbers reported represent how many participants correctly guessed an arm in which they were assigned to.
within first 3 weeks
Adverse Effects
Time Frame: up to 12 weeks

Patients will be asked to report any adverse effects they experience at any time during the 12-week study period.

An adverse event in this study refers to any undesirable or unintended medical occurrence experienced by a participant during the trial, which may or may not be related to the use of intranasal theophylline.
up to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jay F Piccirillo, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 24, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 4, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 13, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202209062

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID-19

Clinical Trials on theophylline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings