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

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: theophylline
Drug: Placebo

Registration Number: NCT05947643

Lead Sponsor: Washington University School of Medicine

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Theophylline	theophylline	Participants will dissolve the contents of the 400 mg theophylline capsules (experimental) into the sinus rinse bottle containing nasal saline.
Placebo	Placebo	Participant will dissolve the contents of the identical-appearing lactose capsules (control) into the sinus rinse bottle containing nasal saline.

Primary Outcome Measures

Name	Time	Method
Clinical Global Impression - Improvement Scale	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

Secondary Outcome Measures

Name	Time	Method
Olfactory Dysfunction Outcomes Rating	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.
Adverse Effects	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.
Assessment of Adherence	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.
Assessment of Blind	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.

Trial Locations

Locations (1): Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States