Condition category
Ear, Nose and Throat
Date applied
30/05/2020
Date assigned
02/06/2020
Last edited
02/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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
fggarciahuidobro@uc.cl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Francisco Garcia-Huidobro

ORCID ID

https://orcid.org/0000-0002-5607-0740

Contact details

Marcoleta 352
Santiago
8330033
Chile
+56 (0)997459771
fggarciahuidobro@uc.cl

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

170728010

Study information

Scientific title

Neuroplasticity assessment using fMRI after olfactory training in post-surgical olfactory impaired patients

Acronym

NOTFMRI

Study hypothesis

Olfactory training will induce neuroplasticity processes on associated olfactory areas in patients with post-surgical olfactory dysfunction.

Ethics approval

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

Study design

Single-center interventional randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format

Condition

Post-surgical olfactory dysfunction

Intervention

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.

Intervention type

Other

Phase

Drug names

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

01/05/2017

Overall trial end date

01/05/2021

Reason abandoned (if study stopped)

Eligibility

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

Participant type

Patient

Age group

Adult

Gender

Both

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

01/10/2017

Recruitment end date

31/12/2020

Locations

Countries of recruitment

Chile

Trial participating centre

Pontificia Universidad Catolica de Chile
Marcoleta 352
Santiago
8330033
Chile

Sponsor information

Organisation

Pontifical Catholic University of Chile

Sponsor details

Marcoleta 352
Santiago
8330033
Chile
+56 (0)223548173
cecmeduc@med.puc.cl

Sponsor type

University/education

Website

http://www.uc.cl/

Funders

Funder type

Government

Funder name

Fondo Nacional de Desarrollo Científico y Tecnológico

Alternative name(s)

National Fund for Scientific and Technological Development, El Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Chile

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

01/07/2020

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/06/2020: Trial's existence confirmed by the scientific ethics committee of Pontificia Universidad Catolica medical faculty.