Respiratory Tract InfectionNCT07149428
Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)
An observational study of Respiratory Tract Infection and Smell Disorder, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 1 site in United States.
Trial summary
Background: Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Tract Infection, Smell Disorder, Influenza
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 14 Oct 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study will enroll adults aged 18 and older who are fluent in English and able to provide informed consent and comply with study procedures. Participants will include both healthy volunteers with normal smell and individuals with olfactory dysfunction of varying causes, such as post viral (including COVID-19), sinonasal disease, chemical exposure, or chemotherapy-related smell loss. To maintain consistency, preference will be given to participants who have experienced smell loss within the past year, through those with longer durations of dysfunction may be included.
Who may be able to join
- To be eligible to participate in this study, an individual must meet all the following criteria:
- Adult subjects, any sex, aged 18 or older.
- Ability to understand and willingness to sign a written informed consent document.
- Willingness and ability to comply with and participate in all study procedures and availability for the duration of the study.
- Due to the extensive questionnaires (administered in English language only) that participants must complete independently, fluency in the English language is needed. Hence, participants must be able to read and understand English.
- To maintain consistency in the study, we will prioritize enrolling individuals who have experienced olfactory loss for no more than one year. However, the duration of olfactory dysfunction can vary significantly, often due to delayed awareness or recognition of the condition. For instance, anosmia and hyposmia are frequently reported as long-term consequences of infections, meaning some participants may have experienced prolonged dysfunction. Given this variability, we will treat the duration of olfactory loss as a potential confounding factor in our data analysis, ensuring that its influence is appropriately accounted for when interpreting the results. Other than healthy controls, participants reporting smell loss must also meet one or more of the following criteria to be eligible for the study:
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- General Smell Loss:
- Individuals who have experienced any degree of smell loss or olfactory dysfunction, regardless of the cause. This includes both partial, complete to distorted loss of the sense of smell (hyposmia, anosmia or parosmia).
- Post-COVID-19 or Virus-Related Smell Loss:
- Individuals experiencing olfactory dysfunction due to COVID-19, influenza or other respiratory viruses, leading to both acute and long-term (chronic) smell loss
- Sinonasal Smell Loss:
- Participants diagnosed with smell loss related to sinonasal conditions, such as:
- Chronic Rhinosinusitis: Long-term inflammation of the sinuses that impairs olfactory function.
- Nasal Polyps: Growths in the nasal passage that obstruct airflow and affect the sense of smell.
- Exposure to Toxic Chemicals:
- Patients who have encountered olfactory dysfunction due to exposure to harmful chemicals or environmental toxins that can impair the olfactory receptors or neural pathways responsible for the sense of smell.
- 5. Chemotherapy-Induced Smell Loss:
- Individuals who have experienced smell loss as a side effect of undergoing chemotherapy. This includes patients who are in active treatment as well as those who have completed chemotherapy but continue to suffer from olfactory impairment.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Compromised cognitive ability: Including dementia, intellectual disability, or severe learning disorders, traumatic brain injury,
- Major psychotic and neurological condition: Examples include schizophrenia, bipolar disorder, Parkinson's disease, and multiple sclerosis, epilepsy.
- Normosmia (healthy) controls must not have:
- -Any history of smell or taste loss.
- -Prior nasal surgery.
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- Acute or chronic olfactory disorders.
- Diagnosis of depression or anxiety.
- None of the participants should be current smokers or consume drugs such as cocaine, heroin, opioids, or marijuana.
- Pregnancy
- Participants who report moderate depressive symptoms (BDI >= 20) but do not have a formal diagnosis of depression will not be automatically excluded from the study. Instead, their responses will be flagged for clinical review and referral. If, upon follow-up, a clinical diagnosis of depression is confirmed, they may be excluded in accordance with the study's exclusion criteria. Participants who indicate any level of suicidality on question 9 will be evaluated on a case-by-case basis. If there is any indication of risk, they will be referred for immediate clinical evaluation. Depending on the outcome and the risk level determined, a decision will be made regarding their continued participation, with participant safety as the highest priority.
- fMRI-Specific Exclusion Criteria
- -Metallic implants, such as pacemakers, cochlear implants, or orthopedic devices, can pose safety risks during an MRI scan due to the strong magnetic fields used in the procedure. These implants can also cause artifacts in the MRI images, distorting the data and making it difficult to obtain accurate results.
- Non-removable piercings can also cause safety risks and image artifacts during MRI scans. These piercings may heat up or move in response to the magnetic fields, potentially causing injury or discomfort to the participant.
- Permanent makeup and tattoos, particularly those containing metallic pigments, can pose risks during MRI due to the potential for heating or movement of the pigments. These effects can cause discomfort or burns and will also create artifacts in the MRI images.
- Pregnancy is an exclusion criterion for MRI studies due to the potential risks to the fetus from the strong magnetic fields and radiofrequency energy used in the procedure. Additionally, pregnant participants will find it uncomfortable to lie still in the MRI machine for extended periods, which could affect the quality of the images.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222, ccopr@nih.gov
Anna Clements Centeno, (301) 451-1215, anna.clements@nih.gov
About this study
Background:
Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should.
Read more
Objective:
To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time.
Eligibility:
People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed.
Design:
Participants will have 5 study visits over 1 year. They will have various tests and procedures:
Smell tests. They will have several tests that involve smelling different items and answering questions.
Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits.
Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner.
Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap.
Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose.
Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages.
Samples of blood, urine, and nasal fluid will be taken.
Read the detailed description
Study Description:
This pilot study investigates the mechanisms of parosmia, a qualitative olfactory dysfunction increasingly seen after COVID-19, by examining functional and structural brain changes and peripheral inflammation. Using neuroimaging and biochemical analysis, it aims to distinguish parosmia from other olfactory disorders and provide a foundation for future diagnostic and therapeutic approaches.
Objectives:
Primary objective:
- Evaluate the feasibility, validity, and methodological framework for deep phenotyping of acquired chemosensory disorders.
- Examine task-based functional connectivity patterns from the olfactory bulb to higher-order central processing regions across groups with varying olfactory symptoms.
- Associate central findings with peripheral inflammatory patterns at the olfactory mucosa.
Secondary Objective:
-Investigate the differences and longitudinal changes in white matter microstructural integrity associated with the progression and recovery of olfactory dysfunctions across the recruited patient population.
Tertiary objective:
-Investigate the psychophysiological impacts of altered smell perception, with an emphasis on its negative effects on dietary habits, oral health, and cognitive functions.
Endpoints:
Co-Primary Endpoints:
To identify functional connectivity differences across subgroups, with focus on parosmia. The study hypothesizes that parosmia patients exhibit neuroinflammation at the olfactory bulb or in the amygdala and hippocampus, leading to distorted valence perception. Altered connectivity between primary and secondary olfactory cortices is expected, differing significantly from hyposmia and, to a lesser extent, anosmia. These connectivity changes are expected to correlate with variations in smell function to uncover disrupted neural pathways underlying parosmia.
To identify local inflammatory signatures at the olfactory mucosa that are associated with chemosensory dysfunction and altered functional connectivity.
Secondary Endpoints:
To evaluate whether changes in functional connectivity are associated with structural alterations, specifically reduced axonal myelination between primary and secondary olfactory cortices (amygdala and hippocampus), in parosmia patients (along with their symptoms graph) compared to healthy controls and, to a lesser extent, anosmia patients. Longitudinal analysis will determine if these structural changes lead to higher-order neural degeneration or other significant brain alterations.
Tertiary endpoints:
To investigate whether regions with structural and functional differences correlate with the duration and severity of smell loss, and to assess the impact of prolonged smell dysfunction on psychological health, eating behaviors, oral health, and quality of life.
- Conditions
- Respiratory Tract Infection, Smell Disorder, Influenza, Rhinosinusitis, COVID-19, Depression
- Keywords
- SMELL, Chemotherapy, chemicals, Mood, Diet, Neuroimaging, electrobulbogram, fMRI, Cognition, Toxins
- Medical subject headings
- Respiratory Tract Infections, Olfaction Disorders, Influenza, Human, Rhinosinusitis, COVID-19, Depression, Anosmia
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 |
|---|---|---|
| Anosmia | participants with complete loss of smell | |
| Hyposmia | participants with reduced smell sensitivity | |
| Normosmia (Healthy control cohort) | participants with normal smell function | |
| Parosmia | participants with a distorted smell perception |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity Differences in Olfactory Dysfunction
differences in functional brain connectivity between parosmia, anosmia and hyposmia groups, assessed longitudinally.
Measured: baseline, 3, 6, 9 and 12 months
Secondary outcomes (2)
Structural Brain Changes in Olfactory Dysfunction
Structural brain architecture differences in olfactory-related regions, measured with neuroimaging.
Measured: baseline, 3, 6, 9 and 12 months
Cognitive, Mood and Dietary Impact of Olfactory Dysfunction
Associations between olfactory function and changes in cognition, depressive symptoms and dietary habits, evaluated through surveys and behavioral measures.
Measured: baseline, 3, 6, 9 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2025
- Study start1 Oct 2026
- Primary completion30 Sep 2030 (estimated)
- Study completion14 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Tract InfectionStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joshua M Levy, M.D., Principal investigator, National Institute on Deafness and Other Communication Disorders (NIDCD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07149428
- Sponsor's protocol ID
- 10002331
- Other IDs
- 002331-DC
- Status last verified
- 7 Oct 2026
- First submitted
- 29 Aug 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)
- ClinicalTrials.gov ID
- NCT07149428
- Acronym / sponsor ID
- 10002331
- Conditions
- Respiratory Tract Infection, Smell Disorder, Influenza, Rhinosinusitis, COVID-19, Depression
- Keywords
- SMELL, Chemotherapy, chemicals, Mood, Diet, Neuroimaging, electrobulbogram, fMRI
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)US National Institutes of Health
- Study start
- 1 Oct 2026 (actual)
- Primary completion
- 30 Sep 2030 (estimated)
- Study completion
- 14 Oct 2030 (estimated)
- First posted
- 2 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should.
Objective:
To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time.
Eligibility:
People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed.
Design:
Participants will have 5 study visits over 1 year. They will have various tests and procedures:
Smell tests. They will have several tests that involve smelling different items and answering questions.
Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits.
Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner.
Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap.
Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose.
Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages.
Samples of blood, urine, and nasal fluid will be taken.
Detailed description
Study Description:
This pilot study investigates the mechanisms of parosmia, a qualitative olfactory dysfunction increasingly seen after COVID-19, by examining functional and structural brain changes and peripheral inflammation. Using neuroimaging and biochemical analysis, it aims to distinguish parosmia from other olfactory disorders and provide a foundation for future diagnostic and therapeutic approaches.
Objectives:
Primary objective:
- Evaluate the feasibility, validity, and methodological framework for deep phenotyping of acquired chemosensory disorders.
- Examine task-based functional connectivity patterns from the olfactory bulb to higher-order central processing regions across groups with varying olfactory symptoms.
- Associate central findings with peripheral inflammatory patterns at the olfactory mucosa.
Secondary Objective:
-Investigate the differences and longitudinal changes in white matter microstructural integrity associated with the progression and recovery of olfactory dysfunctions across the recruited patient population.
Tertiary objective:
-Investigate the psychophysiological impacts of altered smell perception, with an emphasis on its negative effects on dietary habits, oral health, and cognitive functions.
Endpoints:
Co-Primary Endpoints:
To identify functional connectivity differences across subgroups, with focus on parosmia. The study hypothesizes that parosmia patients exhibit neuroinflammation at the olfactory bulb or in the amygdala and hippocampus, leading to distorted valence perception. Altered connectivity between primary and secondary olfactory cortices is expected, differing significantly from hyposmia and, to a lesser extent, anosmia. These connectivity changes are expected to correlate with variations in smell function to uncover disrupted neural pathways underlying parosmia.
To identify local inflammatory signatures at the olfactory mucosa that are associated with chemosensory dysfunction and altered functional connectivity.
Secondary Endpoints:
To evaluate whether changes in functional connectivity are associated with structural alterations, specifically reduced axonal myelination between primary and secondary olfactory cortices (amygdala and hippocampus), in parosmia patients (along with their symptoms graph) compared to healthy controls and, to a lesser extent, anosmia patients. Longitudinal analysis will determine if these structural changes lead to higher-order neural degeneration or other significant brain alterations.
Tertiary endpoints:
To investigate whether regions with structural and functional differences correlate with the duration and severity of smell loss, and to assess the impact of prolonged smell dysfunction on psychological health, eating behaviors, oral health, and quality of life.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Anosmia | – | –participants with complete loss of smell |
| Hyposmia | – | –participants with reduced smell sensitivity |
| Normosmia (Healthy control cohort) | – | –participants with normal smell function |
| Parosmia | – | –participants with a distorted smell perception |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study will enroll adults aged 18 and older who are fluent in English and able to provide informed consent and comply with study procedures. Participants will include both healthy volunteers with normal smell and individuals with olfactory dysfunction of varying causes, such as post viral (including COVID-19), sinonasal disease, chemical exposure, or chemotherapy-related smell loss. To maintain consistency, preference will be given to participants who have experienced smell loss within the past year, through those with longer durations of dysfunction may be included.
Key inclusion criteria (19 listed)
- To be eligible to participate in this study, an individual must meet all the following criteria:
- Adult subjects, any sex, aged 18 or older.
- Ability to understand and willingness to sign a written informed consent document.
- Willingness and ability to comply with and participate in all study procedures and availability for the duration of the study.
- Due to the extensive questionnaires (administered in English language only) that participants must complete independently, fluency in the English language is needed. Hence, participants must be able to read and understand English.
Key exclusion criteria (16 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Compromised cognitive ability: Including dementia, intellectual disability, or severe learning disorders, traumatic brain injury,
- Major psychotic and neurological condition: Examples include schizophrenia, bipolar disorder, Parkinson's disease, and multiple sclerosis, epilepsy.
- Normosmia (healthy) controls must not have:
- -Any history of smell or taste loss.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Functional Connectivity Differences in Olfactory Dysfunction
Time frame: baseline, 3, 6, 9 and 12 months
differences in functional brain connectivity between parosmia, anosmia and hyposmia groups, assessed longitudinally.
2 secondary outcomes
Structural Brain Changes in Olfactory Dysfunction
Time frame: baseline, 3, 6, 9 and 12 months
Cognitive, Mood and Dietary Impact of Olfactory Dysfunction
Time frame: baseline, 3, 6, 9 and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joshua M Levy, M.D. principal investigator
National Institute on Deafness and Other Communication Disorders (NIDCD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Respiratory Tract Infection and Smell Disorder, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna E Clements Centeno ((301) 451-1215, anna.clements@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Connectivity Differences in Olfactory Dysfunction (time frame: baseline, 3, 6, 9 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.