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

NCT06020937 | Not Yet Recruiting

• 1 other identifier: UniCT192023
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Trigeminal component

  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

Study Arms (3)

Control

Healthy patients

Diagnostic Test: TDI; Diagnostic Test: Trigeminal Test; Diagnostic Test: Visual Analogue Scale Ratings; Diagnostic Test: Quality of smell Questionnaire

Multiple Sclerosis 1

Patients with multiple Sclerosis and Trigeminal disorders

Diagnostic Test: TDI; Diagnostic Test: Trigeminal Test; Diagnostic Test: Cognitive Evaluation by Montreal Cognitive Assessment; Diagnostic Test: Anxiety and Depression questionnaire; Diagnostic Test: Visual Analogue Scale Ratings; Diagnostic Test: Quality of smell Questionnaire

Multiple Sclerosis 2

Patients with Multiple Sclerosis without trigeminal concerns

Diagnostic Test: TDI; Diagnostic Test: Trigeminal Test; Diagnostic Test: Cognitive Evaluation by Montreal Cognitive Assessment; Diagnostic Test: Anxiety and Depression questionnaire; Diagnostic Test: Visual Analogue Scale Ratings; Diagnostic Test: Quality of smell Questionnaire

Interventions

TDI DIAGNOSTIC_TEST

Sniffin' Sticks Threshold and Identification Test

Control; Multiple Sclerosis 1; Multiple Sclerosis 2

Trigeminal Test DIAGNOSTIC_TEST

Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response

Control; Multiple Sclerosis 1; Multiple Sclerosis 2

Cognitive Evaluation by Montreal Cognitive Assessment DIAGNOSTIC_TEST

Montreal Cognitive assessment

Multiple Sclerosis 1; Multiple Sclerosis 2

Anxiety and Depression questionnaire DIAGNOSTIC_TEST

Specific test to evaluate patient's mood

Multiple Sclerosis 1; Multiple Sclerosis 2

Visual Analogue Scale Ratings DIAGNOSTIC_TEST

* 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)

Control; Multiple Sclerosis 1; Multiple Sclerosis 2

Quality of smell Questionnaire DIAGNOSTIC_TEST

Patients will answer to a validated questionnaire

Control; Multiple Sclerosis 1; Multiple Sclerosis 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Catania: lead
• University of Roma La Sapienza: collaborator
• Hospital General Universitario Santa Lucia: collaborator
• Klinik und Poliklinik fur Kinderheilkunde: collaborator

Study Sites (1)

Arianna Di Stadio

Catania, Sicily, 95121, Italy

Location

Related Publications (15)

• Hummel T, Frasnelli J. The intranasal trigeminal system. Handb Clin Neurol. 2019;164:119-134. doi: 10.1016/B978-0-444-63855-7.00008-3.

  PMID: 31604542 BACKGROUND

• Frasnelli J, Manescu S. The intranasal trigeminal system. In: Buettner A, editor. Dordrecht; 2017. p. 881-95

  BACKGROUND

• Hummel T, Iannilli E, Frasnelli J, Boyle J, Gerber J. Central processing of trigeminal activation in humans. Ann N Y Acad Sci. 2009 Jul;1170:190-5. doi: 10.1111/j.1749-6632.2009.03910.x.

  PMID: 19686136 BACKGROUND

• Daiber P, Genovese F, Schriever VA, Hummel T, Mohrlen F, Frings S. Neuropeptide receptors provide a signalling pathway for trigeminal modulation of olfactory transduction. Eur J Neurosci. 2013 Feb;37(4):572-82. doi: 10.1111/ejn.12066. Epub 2012 Dec 3.

  PMID: 23205840 BACKGROUND

• Doty RL, Brugger WE, Jurs PC, Orndorff MA, Snyder PJ, Lowry LD. Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol Behav. 1978 Feb;20(2):175-85. doi: 10.1016/0031-9384(78)90070-7. No abstract available.

  PMID: 662939 BACKGROUND

• Mihara S, Shibamoto T. The role of flavor and fragrance chemicals in TRPA1 (transient receptor potential cation channel, member A1) activity associated with allergies. Allergy Asthma Clin Immunol. 2015 Mar 16;11(1):11. doi: 10.1186/s13223-015-0074-0. eCollection 2015.

  PMID: 25897313 BACKGROUND

• Scheibe M, Schulze S, Mueller CA, Schuster B, Hummel T. Intranasal trigeminal sensitivity: measurements before and after nasal surgery. Eur Arch Otorhinolaryngol. 2014 Jan;271(1):87-92. doi: 10.1007/s00405-013-2466-4. Epub 2013 Apr 9.

  PMID: 23568039 BACKGROUND

• Zhao K, Jiang J, Blacker K, Lyman B, Dalton P, Cowart BJ, Pribitkin EA. Regional peak mucosal cooling predicts the perception of nasal patency. Laryngoscope. 2014 Mar;124(3):589-95. doi: 10.1002/lary.24265. Epub 2013 Jun 28.

  PMID: 23775640 BACKGROUND

• Li C, Farag AA, Maza G, McGhee S, Ciccone MA, Deshpande B, Pribitkin EA, Otto BA, Zhao K. Investigation of the abnormal nasal aerodynamics and trigeminal functions among empty nose syndrome patients. Int Forum Allergy Rhinol. 2018 Mar;8(3):444-452. doi: 10.1002/alr.22045. Epub 2017 Nov 22.

  PMID: 29165896 BACKGROUND

• Konstantinidis I, Tsakiropoulou E, Chatziavramidis A, Ikonomidis C, Markou K. Intranasal trigeminal function in patients with empty nose syndrome. Laryngoscope. 2017 Jun;127(6):1263-1267. doi: 10.1002/lary.26491. Epub 2017 Feb 22.

  PMID: 28224626 BACKGROUND

• Atalar AC, Erdal Y, Tekin B, Yildiz M, Akdogan O, Emre U. Olfactory dysfunction in multiple sclerosis. Mult Scler Relat Disord. 2018 Apr;21:92-96. doi: 10.1016/j.msard.2018.02.032. Epub 2018 Mar 3.

  PMID: 29529530 BACKGROUND

• Zorzon M, Ukmar M, Bragadin LM, Zanier F, Antonello RM, Cazzato G, Zivadinov R. Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study. Mult Scler. 2000 Dec;6(6):386-90. doi: 10.1177/135245850000600605.

  PMID: 11212134 BACKGROUND

• da Silva CJ, da Rocha AJ, Mendes MF, Maia AC Jr, Braga FT, Tilbery CP. Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings with clinical correlation in a series of patients. Mult Scler. 2005 Jun;11(3):282-5. doi: 10.1191/1352458505ms1186oa.

  PMID: 15957508 BACKGROUND

• Riello M, Cecchini MP, Zanini A, Di Chiappari M, Tinazzi M, Fiorio M. Perception of phasic pain is modulated by smell and taste. Eur J Pain. 2019 Nov;23(10):1790-1800. doi: 10.1002/ejp.1453. Epub 2019 Jul 29.

  PMID: 31291496 BACKGROUND

• Di Stadio A, Bernitsas E, La Mantia I, Brenner MJ, Ralli M, Vaira LA, Colizza A, Cavaliere C, Laudani M, Frohman TC, De Vincentiis M, Frohman EM, Altieri M. Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)? Life (Basel). 2023 Jan 13;13(1):226. doi: 10.3390/life13010226.

  PMID: 36676175 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor (temporary)

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 1, 2023
• Study Start: October 30, 2024
• Primary Completion: July 30, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

IT (1)