Smell Training for Loss of Smell After COVID-19

(OTTODC19 Trial)

Overseen By Frank Cloutier, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Université du Québec à Trois-Rivières

Disqualifiers: Chronic rhinosinusitis, Neurodegenerative diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines smell training as a method to assist individuals who lost their sense of smell after COVID-19. Participants will smell different scents twice daily for 12 weeks to determine if it improves their ability to smell. Two groups will participate: one will use scents like rose and eucalyptus, while the other will use scents like coffee and lemon. This trial may suit someone who had COVID-19, continues to have difficulty smelling, and understands French. As an unphased trial, it offers a unique opportunity to contribute to research that could help others regain their sense of smell.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this olfactory training is safe for treating loss of smell after COVID-19?

Research has shown that smell training is a safe method for people who have lost their sense of smell after COVID-19. Studies have found that participants generally handle this approach easily, with no serious side effects reported. The training involves sniffing specific scents, such as rose or coffee, for a short time each day.

In one study, participants who engaged in smell training noticed improvements in their sense of smell without significant negative effects. The process is non-invasive, meaning it doesn't involve surgery or medication, making it a low-risk option for those seeking to regain their sense of smell after COVID-19. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about smell training for loss of smell after COVID-19 because it offers a non-invasive, natural approach that could potentially help the brain relearn how to recognize odors. Unlike current treatments that may include medications or simply waiting for the sense of smell to return on its own, this method actively engages patients in regular sensory exercises. By using specific scents like eucalyptol or coffee aroma, the training aims to stimulate different olfactory pathways, potentially speeding up recovery. This approach is unique because it leverages the brain's plasticity, offering a hands-on solution that empowers patients to take an active role in their healing process.

What evidence suggests that this trial's smell training treatments could be effective for loss of smell after COVID-19?

Research shows that smell training can help people regain their sense of smell after losing it due to COVID-19. In this trial, participants will join one of two chemosensory training groups. One group will use scents such as eucalyptol, phenyl ethanol, orange, and eugenol, while the other will use coffee aroma, cheese aroma, strawberries, and limon. One study found that using different scents during training can speed up recovery. Another study discovered that combining smell training with visual cues helped people regain their sense of smell. However, traditional smell training alone might not work for everyone with COVID-19-related smell loss, as noted in one study. Overall, smell training might help, but results can vary. ^{2 5 6 7 8}

Who Is on the Research Team?

Johannes A Frasnelli, PhD

Principal Investigator

Université du Québec à Trois-Rivières

Are You a Good Fit for This Trial?

This trial is for individuals who had COVID-19 and are now experiencing persistent smell disorders. Participants must be able to give informed consent, understand French, and have internet access with an email.

Inclusion Criteria

I tested positive for COVID-19 and still can't smell properly.

Willing and able to provide written informed consent

Have an internet connection and a working email address

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Meeting

Participants undergo initial olfactory evaluation and receive training instructions

1 day

1 visit (in-person)

Treatment

Participants perform olfactory training with assigned scents for 12 weeks

12 weeks

Self-administered, daily

Final Meeting

Participants undergo final olfactory evaluation after 12 weeks of treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in olfactory function post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Smell training

Trial Overview

The study tests olfactory training (smell training) over 12 weeks using two sets of scents to improve the sense of smell after COVID-19. One group uses rose, orange, clove, eucalyptus; another uses cheese, coffee, strawberries, lemon.

How Is the Trial Designed?

Group I: Chemosensory training group 2 Experimental Treatment 1 Intervention

For 12 weeks, morning and evening, smell four odors namely coffee aroma, cheese aroma, strawberries, and limon, for a total of five minutes per session.

Group II: Chemosensory training group 1 Experimental Treatment 1 Intervention

For 12 weeks, morning and evening, smell four odors namely eucalyptol, phenyl ethanol, Orange, and eugenol, for a total of five minutes per session.

Who Is Running the Clinical Trial?

Université du Québec à Trois-Rivières

Lead Sponsor

Trials

48

Recruited

4,500+

Published Research Related to This Trial

In a clinical trial involving 185 patients with post-COVID-19 olfactory dysfunction, those treated with the anti-inflammatory supplement PEA-LUT alongside olfactory training showed significantly greater improvements in their sense of smell compared to those who received placebo with olfactory training.

The intervention group had a recovery rate of 92%, while only 42% of the control group improved, indicating that PEA-LUT effectively enhances the benefits of olfactory training in restoring olfactory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial. Di Stadio, A., D'Ascanio, L., Vaira, LA., et al.[2023]

Olfactory training significantly improved the sense of smell in patients with olfactory dysfunction after COVID-19, with a strong effect size (SMD = 1.0830) indicating that training was effective in enhancing olfactory scores.

Patients who underwent olfactory training during the acute phase of dysfunction (less than 30 days after onset) experienced greater improvements compared to those with chronic dysfunction, suggesting that earlier intervention may lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Olfactory Training as a Treatment for Olfactory Disorders Caused by Coronavirus Disease-2019: A Systematic Review and Meta-Analysis. Hwang, SH., Kim, SW., Basurrah, MA., et al.[2023]

Olfactory dysfunction (OD) in COVID-19 is linked to damage in sustentacular cells that have ACE-2 receptors, which may lead to prolonged anosmia and increase the risk of neurodegenerative disorders.

Olfactory training (OT) has been shown to be an effective treatment for OD, promoting neural rearrangement and functional connectivity without significant adverse effects, making it a recommended intervention for patients with COVID-induced anosmia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory training for olfactory dysfunction in COVID-19: A promising mitigation amidst looming neurocognitive sequelae of the pandemic. Ojha, P., Dixit, A.[2022]

In a pilot study involving 50 participants (25 in the olfactory training group and 25 in the placebo group), olfactory training (OT) did not improve objective olfactory test scores but significantly enhanced participants' subjective sense of smell after 12 weeks.

The study also found that OT reduced the frequency of parosmia (distorted sense of smell) in the intervention group, suggesting potential benefits of OT for individuals experiencing post-COVID-19 olfactory dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study. Bérubé, S., Demers, C., Bussière, N., et al.[2023]

Olfactory training (OT) is being investigated as a promising treatment for smell disorders in COVID-19 patients, which can significantly affect their quality of life.

This systematic review will assess the effectiveness and safety of OT, providing crucial evidence to support its use in treating smell dysfunction caused by COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smell disorders in COVID-19 patients: role of olfactory training: A protocol for systematic review and meta-analysis. Zhang, Y., Mei, T., Chen, Y., et al.[2023]

Olfactory training (OT) significantly improved the sense of smell in COVID-19 patients with persistent olfactory dysfunction, especially in those who adhered to the training protocol, with continued improvements noted up to 12 months after starting OT.

Among 57 patients studied over 18 months, those who fully adhered to OT showed better psychophysical scores compared to those who did not, highlighting the importance of adherence for recovery, although both groups experienced similar rates of olfactory disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of olfactory training in COVID-19 patients with olfactory dysfunction: a prospective study. Lechien, JR., Vaira, LA., Saussez, S.[2023]

In a study of 52 patients with long COVID-19-related olfactory dysfunction, two-thirds reported subjective improvements in smell and taste, along with a significant reduction in the negative impact on their quality of life.

Olfactory training (OT) showed a modest average effect on smell recovery, but patients who fully complied with the training had a significantly higher chance of clinically meaningful improvement in their olfactory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory training in long COVID-19 patients with lasting symptoms including olfactory dysfunction. Fjaeldstad, AW., Ovesen, T., Stankevice, D., et al.[2023]

In a pilot study involving 27 patients with persistent olfactory dysfunction due to COVID-19, those treated with a combination of oral corticosteroids and olfactory training showed significant improvement in their sense of smell compared to those who only received olfactory training.

The treatment was found to be safe, with only minimal and transient side effects reported by a few participants, indicating that this approach could be a promising option for patients suffering from long-lasting olfactory loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell. Le Bon, SD., Konopnicki, D., Pisarski, N., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9309586/

Intensive Olfactory Training in Post-COVID-19 Patients

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Efficacy of Olfactive Training on Loss of Smell and Taste ...

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This randomized clinical trial assesses the efficacy of bimodal visual-olfactory training and patient-preferred scents vs unimodal olfactory training and ...

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frontiersin.org

frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1457527/full

The effectiveness of olfactory training for chronic ...

The authors suggest that PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone. Also, the ...

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onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/full/10.1002/lary.32275

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This study found that 12 weeks of classical olfactory training is not effective in the treatment of COVID-19 induced olfactory dysfunction.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12121588/

Protocol for olfactory training in persisting COVID-19 ...

Trial design and safety measurements. The SMELL study is a monocentric trial assessing OT in individuals with persisting COVID-19-associated OD.

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jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2839325

Olfactory Dysfunction After SARS-CoV-2 Infection in the ...

This cohort study examines the presence, severity, and patterns of olfactory dysfunction in US adults with and without prior SARS-CoV-2 ...

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pmc.ncbi.nlm.nih.gov/articles/PMC11525399/

Treatment of COVID-19 Associated Olfactory Dysfunction

Efficacy and safety of oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell. Eur Arch ...