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

Multiple Sclerosis Clinical Trial

Official title:

Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06020937
• Other study ID #: UniCT192023
• Status: Not yet recruiting
• Start date: October 30, 2024
• Est. completion date: December 30, 2026

Study information

• Verified date: May 2024
• Source: University of Catania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 30, 2026
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Diagnostic Test:
• TDI
Sniffin' Sticks Threshold and Identification Test
• Trigeminal Test
Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response
• Cognitive Evaluation by Montreal Cognitive Assessment
Montreal Cognitive assessment
• Anxiety and Depression questionnaire
Specific test to evaluate patient's mood
• 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
Patients will answer to a validated questionnaire

Locations

Country	Name	City	State
Italy	Arianna Di Stadio	Catania	Sicily

Sponsors (4)

Lead Sponsor	Collaborator
University of Catania	Hospital General Universitario Santa Lucia, Klinik und Poliklinik fur Kinderheilkunde, University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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 I — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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