xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06020937</url>
    </required_header>
    <id_info>
      <org_study_id>UniCT192023</org_study_id>
      <nct_id>NCT06020937</nct_id>
    </id_info>
    <brief_title>Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis: Case-control Study</brief_title>
    <official_title>Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Catania</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Roma La Sapienza</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hospital General Universitario Santa Lucia</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Klinik und Poliklinik fur Kinderheilkunde</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Catania</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The sensation of smell is influenced by the somatosensory and chemesthetic sensati¬ons of the&#xD;
        nose: for example, the cooling sensation of menthol or the prickle of carbon dioxide from&#xD;
        carbonated drinks. These sensations are mediated in the nose by the trigeminal nerve and&#xD;
        there is increasing evidence that trigeminal and olfactory functions are closely linked and&#xD;
        potentially interdependent. In addition, trigeminal activation is crucial to the perception&#xD;
        of nasal airflow. Some researchers speculate about the impact of trigeminal nerve on the&#xD;
        entire olfactory sensation and about the presence of some specific &quot;trigeminal cells&quot; into&#xD;
        the nose.Patients with Multiple sclerosis (MS) can suffer from quantitative olfactory&#xD;
        disorders that generally are of light entity and do not interfere with daily life activities&#xD;
        but it is important to underline that olfactory loss can be an onset sign of the MS.&#xD;
        Considering the &quot;trigeminal component&quot; in the olfaction, because trigeminal nerve&#xD;
        inflammation is quite common in MS patients due to central and peripheral inflammation, it&#xD;
        could be possible that these patients suffer from changes in the quantitative, but more in&#xD;
        the qualitative smell functions that are generally not identified because poorly&#xD;
        investigated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        From a theoretically point of view pain in the trigeminal nerve increases the surrounding&#xD;
        perception, including the perception of the odors. It has been shown that by using sweet food&#xD;
        it is possible to reduce the level of pain; on the other side, sweet food in contrast to the&#xD;
        bitter one was able to reduce the sensation of odor unpleasantness present with pain&#xD;
        increase.&#xD;
  &#xD;
        To date no studies have investigated the relationship between trigeminal inflammation, odors&#xD;
        and pain in a cohort of patients with MS. This study aims at investigating the possible&#xD;
        correlation between alteration in trigeminal functions and perception of odors using Sniffin'&#xD;
        Stick Threshold, Detection and Identification test and quality smell questionnaire in a&#xD;
        sample of healthy patients compared to MS patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 7, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">March 30, 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>12 Months</target_duration>
    <primary_outcome>
      <measure>Trigeminal component</measure>
      <time_frame>12 months</time_frame>
      <description>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&#xD;
  Trigeminal intensity ratings (How intense is the tickling or cool sensation in the nose? 0 no feeling, 10 very strong feeling)&#xD;
  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&#xD;
  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&#xD;
  The score is the sum of correct lateralizations</description>
    </primary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Multiple Sclerosis</condition>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <description>Healthy patients</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <description>Patients with multiple Sclerosis and Trigeminal disorders</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
      <description>Patients with Multiple Sclerosis without trigeminal concerns</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>TDI</intervention_name>
      <description>Sniffin' Sticks Threshold and Identification Test</description>
      <arm_group_label>Control</arm_group_label>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Trigeminal Test</intervention_name>
      <description>Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response</description>
      <arm_group_label>Control</arm_group_label>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Cognitive Evaluation by Montreal Cognitive Assessment</intervention_name>
      <description>Montreal Cognitive assessment</description>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Anxiety and Depression questionnaire</intervention_name>
      <description>Specific test to evaluate patient's mood</description>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Visual Analogue Scale Ratings</intervention_name>
      <description>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)&#xD;
  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)</description>
      <arm_group_label>Control</arm_group_label>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Quality of smell Questionnaire</intervention_name>
      <description>Patients will answer to a validated questionnaire</description>
      <arm_group_label>Control</arm_group_label>
      <arm_group_label>Multiple Sclerosis 1</arm_group_label>
      <arm_group_label>Multiple Sclerosis 2</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Number of participants: 400, 200 healthy controls, and 200 patients diagnosed with multiple&#xD;
          sclerosis divided as follow: 100 with manifest trigeminal pain 100 without known trigeminal&#xD;
          pathology.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Adult women (age 18 to 55) diagnosed with multiple sclerosis using the 2017 McDonald&#xD;
          Criteria under treatment with Disease Modifying Therapy (DMTs) with or without trigeminal&#xD;
          concerns, or newly diagnosed with MS&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Chronic rhinosinusitis with and without nasal polyposis; current allergic rhinitis;&#xD;
               other nasal issues that lead to olfactory dysfunction&#xD;
  &#xD;
            -  anamnestic COVID with incomplete recovery&#xD;
  &#xD;
            -  Neurodegenerative disorders (Parkinson, Alzheimer, Fronto-temporal Dementia, cognitive&#xD;
               impairment and brain vascular diseases)&#xD;
  &#xD;
            -  History of stroke in the last three years&#xD;
  &#xD;
            -  Depression or any psychiatric condition&#xD;
  &#xD;
            -  intake of drugs with sedating side effects&#xD;
  &#xD;
            -  major health issues that might affect olfactory function (e.g., significant renal&#xD;
               insufficiency, uncontrolled diabetes)&#xD;
  &#xD;
            -  Chronic alcoholism / drug abuse&#xD;
  &#xD;
            -  Severe head trauma&#xD;
  &#xD;
            -  Severe facial injuries&#xD;
  &#xD;
            -  Smoker over 20 cigarettes day or smoking from more than 15 years&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Arianna Di Stadio</name>
        <address>
          <city>Catania</city>
          <state>Sicily</state>
          <zip>95121</zip>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Arianna Di Stadio</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <reference>
      <citation>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.</citation>
      <PMID>31604542</PMID>
    </reference>
    <reference>
      <citation>Frasnelli J, Manescu S. The intranasal trigeminal system. In: Buettner A, editor. Dordrecht; 2017. p. 881-95</citation>
    </reference>
    <reference>
      <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.</citation>
      <PMID>19686136</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>23205840</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>662939</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>25897313</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>23568039</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>23775640</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>29165896</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>28224626</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>29529530</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>11212134</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>15957508</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>31291496</PMID>
    </reference>
    <results_reference>
      <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 Investigating Disease-Modifying Therapy (DMT)? Life (Basel). 2023 Jan 13;13(1):226. doi: 10.3390/life13010226.</citation>
      <PMID>36676175</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 26, 2023</last_update_submitted>
    <last_update_submitted_qc>August 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Catania</investigator_affiliation>
      <investigator_full_name>Arianna Di Stadio</investigator_full_name>
      <investigator_title>Associate Professor (temporary)</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Multiple Sclerosis</mesh_term>
      <mesh_term>Sclerosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>History collection&#xD;
  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&#xD;
  &quot;Sniffin' Sticks&quot; Threshold and Identification Test Perform monorhinal&#xD;
  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)&#xD;
  Quality of smell Questionnaire&#xD;
  Cognitive Evaluation by Montreal Cognitive Assessment&#xD;
  Anxiety and Depression questionnaire&#xD;
  Trigeminal Lateralization</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06020937
  org study id: UniCT192023
  nct id: NCT06020937
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  observational model: Case-Control
  time perspective: Prospective
  measure: Trigeminal component
  time frame: 12 months
  description: 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
  arm group label: Control
  description: Healthy patients
  arm group label: Multiple Sclerosis 1
  description: Patients with multiple Sclerosis and Trigeminal disorders
  arm group label: Multiple Sclerosis 2
  description: Patients with Multiple Sclerosis without trigeminal concerns
  intervention type: Diagnostic Test
  intervention name: TDI
  description: Sniffin' Sticks Threshold and Identification Test
  arm group label: Control
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  intervention type: Diagnostic Test
  intervention name: Trigeminal Test
  description: Test the trigeminal smell answer by a device that releases air and a substance that stimulates the trigeminal response
  arm group label: Control
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  intervention type: Diagnostic Test
  intervention name: Cognitive Evaluation by Montreal Cognitive Assessment
  description: Montreal Cognitive assessment
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  intervention type: Diagnostic Test
  intervention name: Anxiety and Depression questionnaire
  description: Specific test to evaluate patient's mood
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  intervention type: Diagnostic Test
  intervention name: Visual Analogue Scale Ratings
  description: 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)
  arm group label: Control
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  intervention type: Diagnostic Test
  intervention name: Quality of smell Questionnaire
  description: Patients will answer to a validated questionnaire
  arm group label: Control
  arm group label: Multiple Sclerosis 1
  arm group label: Multiple Sclerosis 2
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  contact: 
  country: Italy
  citation: 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
  citation: Frasnelli J, Manescu S. The intranasal trigeminal system. In: Buettner A, editor. Dordrecht; 2017. p. 881-95
  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.
  PMID: 19686136
  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.
  PMID: 23205840
  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.
  PMID: 662939
  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.
  PMID: 25897313
  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.
  PMID: 23568039
  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.
  PMID: 23775640
  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.
  PMID: 29165896
  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.
  PMID: 28224626
  citation: 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
  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.
  PMID: 11212134
  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.
  PMID: 15957508
  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.
  PMID: 31291496
  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 Investigating Disease-Modifying Therapy (DMT)? Life (Basel). 2023 Jan 13;13(1):226. doi: 10.3390/life13010226.
  PMID: 36676175
  responsible party type: Principal Investigator
  investigator affiliation: University of Catania
  investigator full name: Arianna Di Stadio
  investigator title: Associate Professor (temporary)
  mesh term: Multiple Sclerosis
  mesh term: Sclerosis
  sharing ipd: Undecided
  ipd 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