AnosmiaPhase 2Co-STARNCT04422275
Coronavirus Smell Therapy for Anosmia Recovery
A Phase 2 study testing Budesonide, High-Concentration Essential Oil and Low-Concentration Essential Oil in people with Anosmia, run by Washington University School of Medicine at 1 site in United States.
Trial 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%… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Anosmia
- What is being tested?
- Budesonide, High-Concentration Essential Oil and Low-Concentration Essential Oil
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2021to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This will be a virtual or "contactless" clinical trial. Subjects will be recruited through a variety of ways and will complete all baseline and post-intervention assessments via specially designed electronic platforms, including REDCap and digital eHealth assessments. There will be no in-person, on-campus interaction between the members of the study team and research participants.
Convalescent COVID-19 subjects with persistent (i.e. > 3 months) decreased sense of smell, and a score on the UPSIT consistent with decreased olfactory function (< 35 women, < 34 men) will be offered enrollment. This will be a 2 x 2 factorial double-blinded, placebo-controlled, randomized clinical trial.
Subjects will be assigned to one of two nasal saline lavage interventions through a randomization schedule developed by the Study Pharmacist. The package and detailed instructions will be shipped directly to the subject from pharmacy. Subjects will be requested to rinse each nasal cavity once daily for 12 weeks and to keep track of their daily use through a paper dairy or specially created app to track compliance.
Subjects will be assigned to one of two olfactory training interventions through a randomization schedule prepared by the Study Pharmacist. The smell training intervention will be shipped directly to the subject. The subject will be expected to complete the smell training for 12 weeks as instructed. Subjects will be asked to record their daily training on a specially created app and make observations on their smell or taste function at the end of every week.
Outcome assessments will be performed immediately upon completing nasal saline lavage and olfactory training (Week 12) and follow-up (Week 24).
- Conditions
- Anosmia
- Being tested
- Budesonide, High-Concentration Essential Oil, Placebo, Low-Concentration Essential Oil
- Keywords
- COVID, Smell Therapy
- Medical subject headings
- Anosmia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BudesonideDrug
The drug intervention budesonide (0.5 mg /capsule) will be dissolved in 240 ml nasal saline lavage.
High-Concentration Essential OilBehavioural
High-concentration essential oil will include 1 ml of essential oil per jar.
PlaceboDrug
The placebo (lactose monohydrate) drug will be dissolved in 240 ml of nasal saline lavage.
Low-Concentration Essential OilBehavioural
Low-concentration essential oil will include 0.1 ml of essential oil per jar.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo; Behavioral: Low-Concentration Essential Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) was adapted from the original 52-item Questionnaire of Olfactory Disorders. This short-modified version is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. The maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment of normal daily activity. Mean scores in anosmics is 19; hyposmics is 8; and normosmics is 0. Prior studies used a cutoff score of 12.5 to reflect normal vs. abnormal scores.The minimum clinically important difference is 5.2.
Measured: The within subject change in QOD-NS between baseline and assessment time frame.
Global Rating of Smell.
The Global Rating of Smell is a single-item, global rating that asks:
"Overall, please rate your current sense of smell? Excellent, Very Good, Good, Fair, Poor, Absent."
Measured: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
Global Rating of Smell Change.
The Global Rating of Smell Change is a single-item, global rating that asks: "Compared to your sense of smell # weeks ago, how would you rate your change in smell since then? Much better, Somewhat better, Slightly better, Neither better nor worse, Slightly worse, Somewhat worse, or Much worse." The time frame ("#") will be changed to reflect the correct time since enrollment (i.e., 12, or 24 weeks).
Measured: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start1 Jun 2021 (estimated)
- Primary completion1 Jun 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Why it stopped: Funding not received
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnosmiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 2 x 2 factorial design
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jay F. Piccirillo, MD, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04422275
- Sponsor's protocol ID
- PA-18-334
- Acronym
- Co-STAR
- Status last verified
- Feb 2021
- First submitted
- 5 Jun 2020
- Last updated
- 2 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Coronavirus Smell Therapy for Anosmia Recovery
- ClinicalTrials.gov ID
- NCT04422275
- Acronym / sponsor ID
- Co-STAR / PA-18-334
- Conditions
- Anosmia
- Keywords
- COVID, Smell Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not received
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 Jun 2021 (estimated)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 9 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This will be a virtual or "contactless" clinical trial. Subjects will be recruited through a variety of ways and will complete all baseline and post-intervention assessments via specially designed electronic platforms, including REDCap and digital eHealth assessments. There will be no in-person, on-campus interaction between the members of the study team and research participants.
Convalescent COVID-19 subjects with persistent (i.e. > 3 months) decreased sense of smell, and a score on the UPSIT consistent with decreased olfactory function (< 35 women, < 34 men) will be offered enrollment. This will be a 2 x 2 factorial double-blinded, placebo-controlled, randomized clinical trial.
Subjects will be assigned to one of two nasal saline lavage interventions through a randomization schedule developed by the Study Pharmacist. The package and detailed instructions will be shipped directly to the subject from pharmacy. Subjects will be requested to rinse each nasal cavity once daily for 12 weeks and to keep track of their daily use through a paper dairy or specially created app to track compliance.
Subjects will be assigned to one of two olfactory training interventions through a randomization schedule prepared by the Study Pharmacist. The smell training intervention will be shipped directly to the subject. The subject will be expected to complete the smell training for 12 weeks as instructed. Subjects will be asked to record their daily training on a specially created app and make observations on their smell or taste function at the end of every week.
Outcome assessments will be performed immediately upon completing nasal saline lavage and olfactory training (Week 12) and follow-up (Week 24).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 2 x 2 factorial design
| Arm | Type | Receives |
|---|---|---|
| Budesonide & High-Concentration OLF | Active comparator | Drug: Budesonide, Behavioral: High-Concentration Essential OilIn 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. |
| Placebo & High-Concentration OLF | Active comparator | Behavioral: High-Concentration Essential Oil, Drug: PlaceboIn 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. |
| Budesonide & Low-Concentration OLF | Active comparator | Drug: Budesonide, Behavioral: Low-Concentration Essential OilIn 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. |
| Placebo & Low-Concentration OLF | Placebo comparator | Drug: Placebo, Behavioral: Low-Concentration Essential OilIn 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 ).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BudesonideThe drug intervention budesonide (0.5 mg /capsule) will be dissolved in 240 ml nasal saline lavage. | Drug | Budesonide & High-Concentration OLF, Budesonide & Low-Concentration OLF |
| High-Concentration Essential OilHigh-concentration essential oil will include 1 ml of essential oil per jar. | Behavioural | Budesonide & High-Concentration OLF, Placebo & High-Concentration OLF |
| PlaceboThe placebo (lactose monohydrate) drug will be dissolved in 240 ml of nasal saline lavage. | Drug | Placebo & High-Concentration OLF, Placebo & Low-Concentration OLF |
| Low-Concentration Essential OilLow-concentration essential oil will include 0.1 ml of essential oil per jar. | Behavioural | Budesonide & Low-Concentration OLF, Placebo & Low-Concentration OLF |
Primary outcome
University of Pennsylvania Smell Identification Test (UPSIT)
Time frame: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.
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.
3 secondary outcomes
Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS).
Time frame: The within subject change in QOD-NS between baseline and assessment time frame.
Global Rating of Smell.
Time frame: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
Global Rating of Smell Change.
Time frame: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Individual participant dataSharing planned: No
Related trials for Anosmia
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
Recruiting
A Clinical Trial to Study the Effects on the Olfaction Capacity of an Individual Undergoing Skull Base Surgeries Using Cautery vs Scalpel .
Olfaction
Not yet recruiting
Effects of Olfactory Stimuli in Virtual Reality Cue Exposure on Craving and Attentional Bias in Alcohol Use Disorder
Alcohol Use Disorder
Not yet recruitingEarly Phase 1
In Vivo Imaging of the Olfactory Epithelium Using Confocal Laser Endomicroscopy
Endonasal Surgery, Endoscopic Sinus Surgery
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Budesonide, High-Concentration Essential Oil and Low-Concentration Essential Oil in people with Anosmia, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
University of Pennsylvania Smell Identification Test (UPSIT) (time frame: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.