Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis: Case-control Study

May 11, 2026 updated by: Arianna Di Stadio, University of Catania

Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis

The sensation of smell is influenced by the somatosensory and chemesthetic sensati¬ons of the nose: for example, the cooling sensation of menthol or the prickle of carbon dioxide from carbonated drinks. These sensations are mediated in the nose by the trigeminal nerve and there is increasing evidence that trigeminal and olfactory functions are closely linked and potentially interdependent. In addition, trigeminal activation is crucial to the perception of nasal airflow. Some researchers speculate about the impact of trigeminal nerve on the entire olfactory sensation and about the presence of some specific "trigeminal cells" into the nose.Patients with Multiple sclerosis (MS) can suffer from quantitative olfactory disorders that generally are of light entity and do not interfere with daily life activities but it is important to underline that olfactory loss can be an onset sign of the MS. Considering the "trigeminal component" in the olfaction, because trigeminal nerve inflammation is quite common in MS patients due to central and peripheral inflammation, it could be possible that these patients suffer from changes in the quantitative, but more in the qualitative smell functions that are generally not identified because poorly investigated.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

From a theoretically point of view pain in the trigeminal nerve increases the surrounding perception, including the perception of the odors. It has been shown that by using sweet food it is possible to reduce the level of pain; on the other side, sweet food in contrast to the bitter one was able to reduce the sensation of odor unpleasantness present with pain increase.

To date no studies have investigated the relationship between trigeminal inflammation, odors and pain in a cohort of patients with MS. This study aims at investigating the possible correlation between alteration in trigeminal functions and perception of odors using Sniffin' Stick Threshold, Detection and Identification test and quality smell questionnaire in a sample of healthy patients compared to MS patients.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Sicily
      • Catania, Sicily, Italy, 95121
        • Arianna Di Stadio
        • Contact:
          • Arianna Di Stadio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Number of participants: 400, 200 healthy controls, and 200 patients diagnosed with multiple sclerosis divided as follow: 100 with manifest trigeminal pain 100 without known trigeminal pathology.

Description

Inclusion Criteria:

Adult women (age 18 to 55) diagnosed with multiple sclerosis using the 2017 McDonald Criteria under treatment with Disease Modifying Therapy (DMTs) with or without trigeminal concerns, or newly diagnosed with MS

Exclusion Criteria:

  • Chronic rhinosinusitis with and without nasal polyposis; current allergic rhinitis; other nasal issues that lead to olfactory dysfunction
  • anamnestic COVID with incomplete recovery
  • Neurodegenerative disorders (Parkinson, Alzheimer, Fronto-temporal Dementia, cognitive impairment and brain vascular diseases)
  • History of stroke in the last three years
  • Depression or any psychiatric condition
  • intake of drugs with sedating side effects
  • major health issues that might affect olfactory function (e.g., significant renal insufficiency, uncontrolled diabetes)
  • Chronic alcoholism / drug abuse
  • Severe head trauma
  • Severe facial injuries
  • Smoker over 20 cigarettes day or smoking from more than 15 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control
Healthy patients
Diagnostic test: TDI
Sniffin' Sticks Threshold and Identification Test
Diagnostic test: Trigeminal Test
Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response
Diagnostic test: Visual Analogue Scale Ratings
  • Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
  • Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
Diagnostic test: Quality of smell Questionnaire
Patients will answer to a validated questionnaire
Multiple Sclerosis 1
Patients with multiple Sclerosis and Trigeminal disorders
Diagnostic test: TDI
Sniffin' Sticks Threshold and Identification Test
Diagnostic test: Trigeminal Test
Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response
Diagnostic test: Visual Analogue Scale Ratings
  • Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
  • Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
Diagnostic test: Quality of smell Questionnaire
Patients will answer to a validated questionnaire
Diagnostic test: Cognitive Evaluation by Montreal Cognitive Assessment
Montreal Cognitive assessment
Diagnostic test: Anxiety and Depression questionnaire
Specific test to evaluate patient's mood
Multiple Sclerosis 2
Patients with Multiple Sclerosis without trigeminal concerns
Diagnostic test: TDI
Sniffin' Sticks Threshold and Identification Test
Diagnostic test: Trigeminal Test
Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response
Diagnostic test: Visual Analogue Scale Ratings
  • Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
  • Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)
Diagnostic test: Quality of smell Questionnaire
Patients will answer to a validated questionnaire
Diagnostic test: Cognitive Evaluation by Montreal Cognitive Assessment
Montreal Cognitive assessment
Diagnostic test: Anxiety and Depression questionnaire
Specific test to evaluate patient's mood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trigeminal component
Time Frame: 12 months

One bottle contains 10ml Eucalyptol (pure / 99%), the other bottle contains only air 15ml stimuli would be released from both bottles using the squeezer device A 3cm long, 4mm inner diameter silicon tubing is placed over the nozzle of each bottle to minimize irritation at the nostrils Silicon tubing should reach beyond the nasal valve area

  • Trigeminal intensity ratings (How intense is the tickling or cool sensation in the nose? 0 no feeling, 10 very strong feeling)

  • The trial can be done on the left nostril, then on the right nostril and this already corresponds to the first presentation for the actual test

    • Total of 20 presentations (10 on each side) with interstimulus interval of around 10 seconds between each presentation, and a longer pause of 30 seconds every 5 presentations
    • The score is the sum of correct lateralizations
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Catania

Collaborators

University of Roma La Sapienza
Hospital General Universitario Santa Lucia
Klinik und Poliklinik fur Kinderheilkunde

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 30, 2026

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

August 22, 2023

First Submitted That Met QC Criteria

August 26, 2023

First Posted (Actual)

September 1, 2023

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UniCT192023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

History collection

Magnetic Resonance Imaging (MRI) 1.5-T Signal scanner; Whole brain scan; T2 FLAIR and double-echo long-TR axial, 3-mm axial and 1mm coronal slices; Olfactory bulb volumetrics

"Sniffin' Sticks" Threshold and Identification Test Perform monorhinal

Visual Analogue Scale Ratings Smell ability (How is your sense of smell right now? 0 cannot smell, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal) Nasal breathing (How well can you breathe through your nose right now? 0 complete nasal obstruction, 1-3 severe impairment, 4-6 moderate impairment, 7-9 mild impairment, 10 normal)

Quality of smell Questionnaire

Cognitive Evaluation by Montreal Cognitive Assessment

Anxiety and Depression questionnaire

Trigeminal Lateralization

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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