Olfactory Training for Loss of Smell

Overseen By Michael Cheng, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Malignant pathology, Sinus surgery, Radiation, Rhinosinusitis, Neurocognitive disorder, others

Compensation: Varies

Number of Visits: 9

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The investigators hypothesize that patients undergoing endoscopic endonasal skull base surgery experience clinically meaningful and modifiable disruptions in postoperative chemosensory function and quality of life, and the investigators further hypothesize that olfactory training in the postoperative period may significantly hasten normalization of patients' chemosensory perturbations. This tailored prospective study seeks to fulfill a significant gap in the understanding of the characteristics, implications, and treatment options for postoperative olfactory and gustatory impairment following endoscopic endonasal skull base surgery.

Will I have to stop taking my current medications?

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

Is olfactory training safe for humans?

The research does not report any safety concerns for olfactory training, suggesting it is generally safe for humans. ^{1 2 3 4 5}

How does olfactory training differ from other treatments for loss of smell?

Olfactory training is unique because it involves regularly smelling specific odors to help improve the sense of smell, unlike other treatments that may not focus on sensory rehabilitation. It is the only evidence-based treatment for post-viral olfactory dysfunction and can potentially benefit psychological functioning by targeting neuroinflammation. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Olfactory Training for Loss of Smell?

Research shows that olfactory training, which involves regularly smelling certain odors, can significantly improve the ability to identify, discriminate, and detect smells in people with smell disorders. This training has been effective in various conditions, including post-infectious and traumatic smell loss, and is considered a promising addition or alternative to existing treatments for olfactory dysfunction. ^{4 7 10 11 12}

Who Is on the Research Team?

Nicholas Rowan, MD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals with benign tumors at the base of their skull who haven't had previous surgeries or treatments in that area, no history of chronic sinus issues, neurocognitive disorders, or intrinsic problems with smell and taste. Those with pacemakers, gastrectomy, or malignant tumors are excluded.

Inclusion Criteria

I have a non-cancerous tumor near the base of my skull.

Exclusion Criteria

I have a long-term history of sinus infections.

You have a history of brain-related memory or thinking problems.

History of cardiac pacemaker

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative

Baseline assessments of olfactory function and quality of life using various questionnaires

1 visit

1 visit (in-person)

Post-operative Treatment

Participants receive either placebo or treatment olfactory training kits to assess changes in olfactory function

3 months

2 weeks post-operative, 1 month post-operative, 3 months post-operative

Follow-up

Participants are monitored for changes in quality of life and olfactory function

6 months

6 months post-operative

What Are the Treatments Tested in This Trial?

Interventions

• Olfactory training
• Placebo training

Trial Overview The study tests if olfactory training after surgery can improve the sense of smell and quality of life faster compared to a placebo training. It's designed to understand how surgery affects smell and taste and whether specific postoperative exercises can help recovery.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Participants receive treatment olfactory training kits that contain essential oils that have scents (lavender, lemon, clove, eucalyptus)

Group II: Placebo Placebo Group 1 Intervention

Participants receive placebo olfactory training kits that only contain medium chain triglycerides that lack any discernible odor

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

North American Skull Base Society

Collaborator

Trials

2

Recruited

110+

Published Research Related to This Trial

Olfactory training (OT) may not only help improve the sense of smell in individuals with olfactory disorders but could also enhance psychological functioning, potentially benefiting cognitive and emotional processes due to the direct connection between the olfactory bulb and the limbic system.

The review highlights the need for more research on OT, including its molecular and neuroanatomical effects, to better understand its role in supporting cognitive functions and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory training - Thirteen years of research reviewed. Pieniak, M., Oleszkiewicz, A., Avaro, V., et al.[2022]

In a study of 153 patients with post-infectious olfactory dysfunction (PIOD) receiving olfactory training, the presence of parosmia was linked to significant improvements in olfactory discrimination and identification, especially in those with lower baseline olfactory function.

Older patients showed more significant improvements in odor threshold, suggesting that age may play a role in recovery outcomes for olfactory function after training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parosmia is Associated with Relevant Olfactory Recovery After Olfactory Training. Liu, DT., Sabha, M., Damm, M., et al.[2021]

Olfactory training can lead to a slight improvement in odor detection thresholds in patients with traumatic anosmia, as shown by significant decreases in PEA thresholds after 6 months of training in both the 4-odorant and PEA groups.

However, while the PEA group showed a significant increase in odor identification scores, the 4-odorant group did not, indicating that the type of training may influence outcomes, and further research is needed to assess the overall clinical benefits of olfactory training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on odor identification in patients with traumatic anosmia. Jiang, RS., Twu, CW., Liang, KL.[2020]

A meta-analysis of 13 studies demonstrated that smell training significantly improves olfactory abilities, particularly in smell identification and discrimination, with large effect sizes.

The effectiveness of smell training varies based on the duration of training and the underlying cause of the smell disorder, suggesting it could be a valuable addition to current treatment options for olfactory dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of olfactory training: a meta-analysis. Sorokowska, A., Drechsler, E., Karwowski, M., et al.[2022]

Olfactory training using phenyl ethyl alcohol (PEA) significantly improved odor detection thresholds in 10 out of 42 patients with traumatic anosmia, compared to only 2 out of 39 patients using mineral oil, indicating the efficacy of PEA in enhancing olfactory function.

The study suggests that olfactory training with PEA is a promising intervention for patients with anosmia following head injuries, although no significant changes were observed in olfactory bulb volume or overall smell identification scores between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on the odor threshold in patients with traumatic anosmia. Jiang, RS., Twu, CW., Liang, KL.[2018]

Topical aminophylline, when used alongside olfactory training, significantly improved smell identification test (SIT) scores in patients with hyposmia or anosmia, with an 85% increase compared to a 55% increase in the control group using saline.

The study suggests that the improvement in olfactory function may be linked to changes in cellular signaling pathways involving cAMP and cGMP, indicating a potential mechanism of action for aminophylline in enhancing olfactory capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Topical Aminophylline on Hyposmia and Anosmia. Jahandideh, H., Rahimi, P., Foroughi Mobarakeh, P., et al.[2022]

In a study involving 200 normosmic individuals, olfactory training (OT) showed no significant improvement in olfactory function after three months or at a one-year follow-up, indicating limited efficacy for those with normal sense of smell.

The study found that longer exposure times in OT did not yield better results, and shorter training sessions were associated with better compliance, suggesting that the duration of training may not be as important as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory training in normosmic individuals: a randomised controlled trial. Heian, IT., Thorstensen, WM., Myklebust, TA., et al.[2023]

Olfactory training is the only therapy for olfactory loss with level 1a evidence supporting its efficacy, making it a valuable option for patients who currently have no other management alternatives.

This therapy is safe, easy to perform, and has the potential to help many patients, although more research is needed to determine the optimal duration and specific protocols for different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evidence for olfactory training in treating patients with olfactory loss. Patel, ZM.[2018]

Olfactory training over 16 weeks significantly improved olfactory function in patients with olfactory dysfunction, with an overall efficacy rate of 40% based on the Sniffin' Sticks olfactory test results.

Patients with less than a year of olfactory dysfunction showed even better improvement, with a 50.9% efficacy rate, indicating that earlier intervention may lead to more successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and associated factors of olfactory training in the treatment of olfactory dysfunction]. Yan, XG., Gao, X., Sun, ZF., et al.[2019]

Olfactory loss affects about 20% of people and can lead to decreased enjoyment in activities like eating, drinking, and even sex, as well as contributing to depression.

Olfactory training (OT), which typically involves smelling four specific scents twice daily for 12 weeks, has been shown to effectively improve olfactory function in individuals with olfactory loss from various causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on olfactory bulb volumes in patients with idiopathic olfactory loss. Mahmut, MK., Musch, M., Han, P., et al.[2020]

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 dysfunction is linked to serious health issues, including neurodegeneration, and requires comprehensive assessment methods, such as rigid nasal endoscopy and validated psychophysical tests, to ensure accurate diagnosis and treatment.

Smell training has been identified as a beneficial intervention for patients experiencing olfactory loss, suggesting that structured rehabilitation can improve outcomes across various causes of smell impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Position paper on olfactory dysfunction. Hummel, T., Whitcroft, KL., Andrews, P., et al.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Olfactory training - Thirteen years of research reviewed. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Parosmia is Associated with Relevant Olfactory Recovery After Olfactory Training. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on odor identification in patients with traumatic anosmia. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of olfactory training: a meta-analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on the odor threshold in patients with traumatic anosmia. [2018]

6. Iran pubmed.ncbi.nlm.nih.gov

The Effect of Topical Aminophylline on Hyposmia and Anosmia. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Olfactory training in normosmic individuals: a randomised controlled trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The evidence for olfactory training in treating patients with olfactory loss. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and associated factors of olfactory training in the treatment of olfactory dysfunction]. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of olfactory training on olfactory bulb volumes in patients with idiopathic olfactory loss. [2020]

11. United Arab Emirates 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. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Position paper on olfactory dysfunction. [2022]