Olfactory DysfunctionNCT07819162
Neural Dissimilarity in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Biologics
An observational study of Olfactory Dysfunction and Chronic Rhinosinusitis With Nasal Polyps (CRSwNP), run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
This project will focus on rehabilitation of olfactory dysfunction in patients with chronic rhinosinusitis with polyps given biological treatment based on functional magnetic resonance imaging. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Olfactory Dysfunction, Chronic Rhinosinusitis With Nasal Polyps (CRSwNP), Functional Magnetic Resonance Imaging (fMRI)
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2027to Jun 2029
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A study population of patients form the out-patient clinic at Copenhagen University Hospital, Rigshospitalet with CRSwNP offered treatment with biologics meeting the criteria for treatment with biologic as stated in the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020) as well as the Danish Medicines Council criteria to be considered for inclusion. Furthermore, healthy controls matched by sex and age recruited through advertisement.
Who may be able to join
- Age 18 years or above
- Olfactory dysfunction (i.e., a TDI score < 30.75)
- Eligible for treatment with biologics (i.e., meeting the Danish criteria for treatment with biologics (40) which includes fulfillment of the EPOS criteria for CRS.
- Either treatment naïve to biologics or had their first injection within a maximum of 48 hours prior to the scan.
- No other obvious explanation for the olfactory dysfunction (including, but not limited to: head trauma, sinus surgery, tumors in the nose or brain, upper respiratory infection, neurological or psychiatric disease)
- Control group: normosmic at baseline (i.e., TDI-score >30.75)
Who cannot join
- Previously recognized loss of sense of smell and taste due to other sinonasal or neurological conditions.
- Neurodegenerative disorders known to cause olfactory deficits (Parkinson's, Alzheimer's, Lewy-Body Dementia, Amyotrophic lateral Sclerosis etc.)
- Other obvious explanation for the OD (i.e., smell loss occurring in relation to one of the following (including, but not limited to): head trauma, sinus surgery, upper respiratory infection.
- Contraindications for MRI scan including:
- Implants or prostheses of magnetic metal
- Metal foreign bodies
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- Pregnancy
- Severe claustrophobia
- Unable to complete the full MRI session.
- Not able to comprehend written and/or spoken Danish language.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, 2100
About this study
Official title: Neural Dissimilarity: A Promising New fMRI-based Measure of Smell? Changes in the Olfactory System Following Treatment for Severe CRSwNP With Monoclonal Antibodies
This project will focus on rehabilitation of olfactory dysfunction in patients with chronic rhinosinusitis with polyps given biological treatment based on functional magnetic resonance imaging.
Read the detailed description
The sense of smell is essential in social interactions, food intake and hazard detection. Olfactory dysfunction (OD) affects approximately 20% of the adults and likely increased following the COVID-19 pandemic. The pandemic highlighted the substantial burden of OD on daily life and well-being.
A common cause of acquired OD is Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) affecting 2-4% of adult Scandinavian population. The vast majority of CRSwNP in this population is driven by type-2 inflammation. Decreased sense of smell is an almost obligatory complaint in severe CRSwNP with an OD prevalences of ~95% and ranked as one of the most important.
OD is the symptom in CRSwNP with greatest effect on health-related quality of life and at the same time remains difficult to treat.
New treatments for patients with severe CRSwNP have recently become available in form of monoclonal antibodies selectively blocking pro-inflammatory cytokines in the type-2-inflammation cascade. These biologics show substantial improvements in self-reported olfactory tests.
Knowledge of neuroanatomical functional and structural correlates to olfactory function has long existed. However, only few have used functional magnetic resonance imaging (fMRI) to investigate OD in CRS patients. Patients with CRS-related OD offer a unique neurobiological model for studying olfactory plasticity as olfaction potentially improves.
This study aims to determine whether improvement in olfaction represented by TDI scores after medical treatment with biologics (anti IL-5 or anti IL-4/13) for severe CRSwNP is accompanied by functional changes in olfactory brain ROIs as represented by differences in representational dissimilarity matrixes (RDMs).
Patients with olfactory dysfunction (OD) due to CRSwNP are recruited before or shortly after their first injection of monoclonal antibodies/biologic therapy. Nasal endoscopy and a validated olfactory test (TDI) are performed. Participants also undergo fMRI, during which they are presented with three different odors that they are asked to categorize. A group of age- and sex-matched healthy controls with normal olfactory function and no disease of the nasal or paranasal sinus system undergoes the same assessments.
All examinations are repeated in both groups after 24 weeks +/- 2 weeks..
By constructing RDMs based on fMRI-data we will invesitage how central olfactory processing changes following 24 weeks of biologic treatment and whether these neural changes are associated with improvements in olfactory performance.
- Conditions
- Olfactory Dysfunction, Chronic Rhinosinusitis With Nasal Polyps (CRSwNP), Functional Magnetic Resonance Imaging (fMRI)
- Keywords
- fMRI, Dupixent, Representational Dissimilarity Analysis, RSA, Representational Dissimilarity Matrix, RDM, Olfactory Dysfunction, OD, CRSwNP, Chronic Rhinosinusitis with Nasal Polyps, Functional MRI, Functional Magnetic Resonance Imaging, Biologics, Biological treatment, Dupilumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CRSwNP with OD | Patients with olfactory dysfunction due to chronic rhinosinusitis with nasal polyps who are navïe to biological treatment | |
| Control | Age-adsjusted, normoosmic and sinus healthy matched controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Representational Similarity Matrix (RDM)
Change in representational dissimilarity matrices (RDMs) derived from functional magnetic resonance imaging (fMRI) data during an odor categorization task. RDMs will be constructed from multivoxel activation patterns elicited by three odor stimuli within predefined olfactory regions of interest
Measured: From enrollment to 24 weeks +/- 2 weeks
Secondary outcomes (2)
Threshold-Discrimination-Identification (TDI) score
Changes in olfactory function measured by Sniffin' Sticks Threshold-Discrimination-Identification (TDI) score
Measured: Baseline and Week 24 (±2 weeks)
Correlation between changes in RDM metrics and changes in TDI score.
Evaluation of the relationship between treatment-related changes in neural olfactory representations and clinical improvements in olfactory performance.
Measured: Baseline and Week 24 (±2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study startJun 2027 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Olfactory DysfunctionStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Klinik für Psychiatrie und Psychotherapie der Universität Regensburg, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
- Responsible party
- Principal investigator, Mads Bolding Rasmussen, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07819162
- Sponsor's protocol ID
- H-26048084
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be made publicly available. De-identified data may be shared with collaborating investigators as part of an established research collaboration and in accordance with ethical approvals, General Data Protection Regulation (GDPR) and the Danish Data Protection Act.