Smell Changes & Efficacy of Nasal Theophylline

NCT03990766 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201901107
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the efficacy and safety of nasal theophylline irrigation in treating smell loss related to a viral respiratory infection. Half the participants will undergo nasal theophylline irrigation treatment while the other half will undergo placebo nasal irrigation with saline alone. All participants will have their sense of smell tested before and after 6 weeks of treatment. All participants will also be regularly asked about any potential side effects related to treatment. In addition, the first 10 participants will have their blood drawn to measure their theophylline level after 1 week of starting treatment to ensure it is not abnormally elevated.

Conditions

Olfactory Disorder; Anosmia; Viral Infection; Theophylline Causing Adverse Effects in Therapeutic Use; Smell Disorder

Keywords

Olfactory dysfunction; Anosmia; Hyposmia; Post-viral; Theophylline; Adverse effects; Smell

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Improvement in Global Rating of Smell Change

  Self-reported change in smell after intervention on a 7-point Likert scale. Response options with corresponding point values: 7) Much better, 6) Somewhat better, 5) Slightly better, 4) Neither better nor worse, 3) Slightly worse, 2) Somewhat worse, and 1) Much worse. The maximum score is 7, and higher values indicate better outcomes. A score of 4 is considered neutral. Scores of 5 or higher indicated clinical improvement.

  6 weeks

Secondary Outcomes (3)

• University of Pennsylvania Smell Identification Test (UPSIT) Total Score Change

  6 weeks

• Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) Score Change

  6 weeks

• Olfactory Dysfunction Outcomes Ratings (ODOR) Score Change

  6 weeks

Study Arms (2)

Theophylline saline irrigation

EXPERIMENTAL

Theophylline 12 mg capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily.

Drug: Theophylline

Placebo saline irrigation

PLACEBO COMPARATOR

Identical-appearing lactose monohydrate capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily.

Drug: Saline Nasal

Interventions

Theophylline DRUG

Theophylline delivered via high-volume, low-pressure nasal saline irrigation

Theophylline saline irrigation

Saline Nasal DRUG

Lactose delivered via high-volume, low-pressure nasal saline irrigation

Placebo saline irrigation

Eligibility Criteria

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

You may qualify if:

• Subjective or clinically diagnosed olfactory dysfunction of 6 months to 36 months duration after a presumed viral upper respiratory infection
• Ability to read, write, and understand English

You may not qualify if:

• Dependence on theophylline for comorbid conditions such as asthma and chronic obstructive pulmonary disease
• History of an allergic reaction to theophylline or other methylxanthines
• Prior sinonasal or anterior skull base surgery
• Nasal polyposis
• 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 (≥40%) interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon-alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Anosmia; Virus Diseases; Olfaction Disorders

Interventions

Theophylline; Sodium Chloride

Condition Hierarchy (Ancestors)

Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The diagnosis of PVOD is by patient history and is thus subject to recall bias. In addition, PVOD treatment response may differ according to the causative virus, which is rarely known. The sample size was limited since all non-life saving clinical research and recruitment were halted at our institution at the time due to COVID-19. Lastly, the optimal dosing of theophylline irrigations is yet to be determined.

Results Point of Contact

• Title: Dr. Jake Lee
• Organization: Washington University School of Medicine

jakejlee@wustl.edu

3143937248

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two randomized arms

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 19, 2019
• Study Start: May 15, 2019
• Primary Completion: January 15, 2021
• Study Completion: January 15, 2021
• Last Updated: March 31, 2022
• Results First Posted: March 31, 2022

Record last verified: 2022-03

Locations

US (1)