Coronavirus Smell Therapy for Anosmia Recovery

NCT04422275 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: PA-18-334
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

As the COVID-19 pandemic spread around the world, anosmia and dysgeusia were quickly recognized as two of the key presenting symptoms. The probability of return of smell is related to severity of smell loss at presentation, but it appears that the loss of sense of smell and taste seems to persist in approximately 10% of the affected patients after 6 months. As a result of COVID-19, it is estimated that within the next 12 months \> 150,000 Americans will suffer permanent loss of smell. The magnitude of this impairment on the health, safety, and quality of life is truly unprecedented and makes post-COVID olfactory disorder a major public health problem. Thus, there is a pressing need to identify effective treatments. The research questions are to determine the effects of steroid nasal saline lavage and olfactory training among adults with post-COVID olfactory dysfunction and identify confounders and modifiers of any observed effects. To answer the research question, the investigators propose a 2 x 2 factorial design blinded randomized clinical trial whereby 220 subjects with documented COVID-19 with anosmia/hyposmia of 12 weeks duration or longer from Missouri, Illinois, and Indiana will be recruited electronically from COVID patient advocacy sites, social media sites, and other internet sources. Enrolled subjects will be randomized to nasal saline lavage with topical budesonide or placebo to address the presumed role of inflammation in the olfactory cleft and each subject will also be randomized to olfactory training with patient-specific, high- or low-concentration essential oil scent to assess the role of olfactory training. Data will be analyzed in a blinded fashion to allow estimation of observed effect size for both anti-inflammatory and olfactory training. This innovative study will exploit the unique opportunities presented by COVID-19. The study will use a high-tech virtual "contactless" research strategy, including eConsent and digital mHealth techniques to obtain rapid answers to the research questions. The interventions are low-cost, readily available, and results of this study can be directly disseminated to the care of COVID-19 patients with anosmia.

Conditions

Anosmia

Keywords

COVID; Smell Therapy

Outcome Measures

Primary Outcomes (1)

• University of Pennsylvania Smell Identification Test (UPSIT)

  The University of Pennsylvania Smell Identification Test (UPSIT) (Sensonics, New Jersey)7 is the most widely accepted olfactory identification test in North America. The UPSIT consists of four 10-page booklets, with a total of 40 items. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender. Normosmia is defined as ≥34 for males and ≥35 for females, and an increase of 4 points or more from baseline indicates a clinically meaningful improvement. UPSIT has high internal reliability across a wide range of populations.

  The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.

Secondary Outcomes (3)

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

  The within subject change in QOD-NS between baseline and assessment time frame.

• Global Rating of Smell.

  12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)

• Global Rating of Smell Change.

  12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)

Study Arms (4)

Budesonide & High-Concentration OLF

ACTIVE COMPARATOR

In this arm, subjects will perform nasal saline lavage (240 ml) with budesonide (0.5mg/capsule) and four different high-concentration (1 ml) essential oils for olfactory training twice daily.

Drug: Budesonide; Behavioral: High-Concentration Essential Oil

Placebo & High-Concentration OLF

ACTIVE COMPARATOR

In this arm, subjects will perform nasal saline lavage (240 ml) with placebo (lactose monohydrate) and four different high-concentration (1 ml) essential oils for olfactory training twice daily.

Behavioral: High-Concentration Essential Oil; Drug: Placebo

Budesonide & Low-Concentration OLF

ACTIVE COMPARATOR

In this arm, subjects will perform nasal saline lavage (240 ml) with budesonide (0.5mg/capsule) and four different low-concentration (0.1 ml) essential oils for olfactory training twice daily.

Drug: Budesonide; Behavioral: Low-Concentration Essential Oil

Placebo & Low-Concentration OLF

PLACEBO COMPARATOR

In this arm, subjects will perform nasal saline lavage (240 ml) with placebo (lactose monohydrate) and four different low-concentration (0.1 ml) essential oils for olfactory training twice daily.

Drug: Placebo; Behavioral: Low-Concentration Essential Oil

Interventions

Budesonide DRUG

The drug intervention budesonide (0.5 mg /capsule) will be dissolved in 240 ml nasal saline lavage.

Budesonide & High-Concentration OLF; Budesonide & Low-Concentration OLF

High-Concentration Essential Oil BEHAVIORAL

High-concentration essential oil will include 1 ml of essential oil per jar.

Budesonide & High-Concentration OLF; Placebo & High-Concentration OLF

Placebo DRUG

The placebo (lactose monohydrate) drug will be dissolved in 240 ml of nasal saline lavage.

Placebo & High-Concentration OLF; Placebo & Low-Concentration OLF

Low-Concentration Essential Oil BEHAVIORAL

Low-concentration essential oil will include 0.1 ml of essential oil per jar.

Budesonide & Low-Concentration OLF; Placebo & Low-Concentration OLF

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult women and men.
• Positive laboratory finding for SARS-CoV-2 (e.g., real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays to detect viral RNA).
• In convalescence from their COVID-19 illness.
• Subjective complaints of reduced olfaction after COVID-19 infection of greater than 3 months duration.
• Reduced olfaction ability as determined by a score of \<35 (women) or \<34 (men) on the University of Pennsylvania Smell Identification Test (UPSIT ).
• Ability to read, write, and understand English.

You may not qualify if:

• History of olfaction disorder prior to COVID-19 infection.
• History of nasal cavity polyps.
• Dependence on prolonged corticosteroid therapy for comorbid conditions, such as asthma and chronic obstructive pulmonary disease.
• History of cerebrospinal fluid leak.
• History of allergy to budesonide or other topical steroids.
• Pregnant or breast feeding or intend to become pregnant during the course of the trial.
• Current infection or history of one of the following infections: Tuberculosis (TB) lung infection, or Herpes infection of the eye.
• Baseline UPSIT score 5 or below, which suggests malingering.
• History of neurodegenerative disease (i.e. Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia).

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Anosmia

Interventions

Budesonide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof of Otolaryngology

Model Details: 2 x 2 factorial design

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 9, 2020
• Study Start: June 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: December 31, 2023
• Last Updated: March 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)