Plain English Summary
Background and study aims
Olfactory dysfunction is the inability to perceive smells. Its treatment is challenging due to limited therapeutic options. Olfactory training has been shown to improve smell identification, discrimination, and the threshold for odour detection of patients with olfactory dysfunction with postinfectious etiology (i.e. after an infection). The aim of this study is to assess the effect of olfactory training in patients with olfactory dysfunction after pituitary surgery (post-surgical etiology) using functional magnetic resonance imaging (fMRI scan) to see if it induces neural (brain) reorganization processes.
Who can participate?
Patients with post-surgical olfactory dysfunction lasting for at least 1 year after endoscopic transsphenoidal pituitary surgery
What does the study involve?
Participants undergo an examination that includes a nasal endoscopic evaluation. They are also tested using an olfactory measurement test (Sniffing Stick test) and undergo an fMRI scan. Participants are randomly allocated to undergo olfactory training for 12 weeks or no treatment. Olfactory training is performed using four essential oils. Participants are instructed to expose themselves twice a day to each odour taking deep sniffs for 30 seconds and resting 10 seconds between each oil. Additionally, they are instructed to evoke a memory or feeling during the odour exposure that is associated with the smell of the essential oil. Participants are contacted monthly to maintain compliance and motivation during the training period. At the end of the 12-week training period, both groups are assessed using the olfactory performance test and fMRI, and the control group receive olfactory training.
What are the possible benefits and risks of participating?
The possible benefits are the partial or complete recovery of olfactory function after olfactory training. This study does not have any risks for the participants.
Where is the study run from?
Pontificia Universidad Catolica de Chile (Chile)
When is the study starting and how long is it expected to run for?
May 2017 to May 2021
Who is funding the study?
Fondo Nacional de Desarrollo Científico y Tecnológico (Chile)
Who is the main contact?
Dr Francisco García-Huidobro
Neuroplasticity assessment using fMRI after olfactory training in post-surgical olfactory impaired patients
Olfactory training will induce neuroplasticity processes on associated olfactory areas in patients with post-surgical olfactory dysfunction.
Approved 05/09/2017, the scientific ethics committee of Pontificia Universidad Catolica medical faculty (Marcoleta 381 – fourth floor, Office 42, Santiago, Chile; +562 (0)23548173; Cecmeduc@med.puc.cl), ref: 170728010
Single-center interventional randomized controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format
Post-surgical olfactory dysfunction
All participants undergo an olfactory measurement test to diagnose olfactory dysfunction and assess severity. Also, they are examined by an ENT specialist's including a complete physical exam and nasofibroscopy, to exclude other conditions that could be causing smell impairment. For the scanning sessions, an odour infusion system is attached to a single air-line, to perform the sniffing paradigm, which is characterized by an odour intake of eucalyptus essential oil through a nasal cannula.
Also, a trigeminal activation paradigm is performed to assess the indemnity of the trigeminal system, characterized by the intake of odourless CO₂ through a nasal cannula. After the first fMRI and olfactory performance assessment, the smell-impaired cohort is randomized into two groups. Participants are randomized by simple randomization using computer-generated random numbers. The allocation is concealed from the research team. No masking is used.
Intervention: Olfactory training for 12 weeks
Control: No treatment
Olfactory training is performed using four essential oils: lemon (limonene 67.08% and b-pinen 12.52%), eucalyptus glovus (1-8-cineole 60%), clove (eugenol 75.49% and eugenol acetate 13.59%) and lavender (linalool 36.53% and linalyl acetate 32.80%). Patients are instructed to expose themselves twice a day to each odour taking deep sniffs for 30 seconds and resting 10 seconds between each oil. Additionally, they are instructed to evoke a memory or feeling during the odour exposure that is associated with the smell of the essential oil. Patients are contacted monthly to maintain compliance and motivation during the training period.
At the end of the 12-week training period, both groups are assessed using olfactory performance test and fMRI, and the control group receive olfactory training.
Primary outcome measure
Activation areas and functional connectivity during olfactory stimulation measured using functional MRI images before olfactory training and 12 weeks after the intervention
Secondary outcome measures
Olfactory function assessed using olfactometric measurements before olfactory training and 12 weeks after the intervention
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Referred post-surgical olfactory dysfunction lasting for at least 1 year
2. Only patients with a definite diagnosis of olfactory dysfunction were finally included
3. No history of psychiatric or neurodegenerative diseases
Target number of participants
Total recruitment of participants is 20 (10 in each arm) and 5 healthy volunteers
Participant exclusion criteria
1. Olfactory dysfunction not related to surgical procedures
2. Associated psychiatric or neurodegenerative diseases
3. Pediatric age
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Pontificia Universidad Catolica de Chile
Fondo Nacional de Desarrollo Científico y Tecnológico
National Fund for Scientific and Technological Development, El Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
The researchers intend to publish initial results as a pilot study in July 2020.
IPD sharing statement
The data that is stored are the demographic data of each patient, the olfactometric results and the fMRI images of each of the patients. This data is private and the ethics committee only authorizes its use by the authors for scientific publication protecting the anonymity of the participants. There are no web links available, and data is stored in the Bioimaging center of the University.
Intention to publish date
Participant level data
Stored in repository
Basic results (scientific)