Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)

NCT07149428 | Not Yet Recruiting

• 2 other identifiers: 10002331002331-DC
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Influenza; Rhinosinusitis; COVID-19; Hyposomia; Smell Disorder; Anosmia; Respiratory Tract Infection; Parosmia; Depression; Normosomia

Keywords

SMELL; Chemotherapy; chemicals; Mood; Diet; Neuroimaging; electrobulbogram; fMRI; Cognition; Toxins

Outcome Measures

Primary Outcomes (1)

• Functional Connectivity Differences in Olfactory Dysfunction

  differences in functional brain connectivity between parosmia, anosmia and hyposmia groups, assessed longitudinally.

  baseline, 3, 6, 9 and 12 months

Secondary Outcomes (2)

• Structural Brain Changes in Olfactory Dysfunction

  baseline, 3, 6, 9 and 12 months

• Cognitive, Mood and Dietary Impact of Olfactory Dysfunction

  baseline, 3, 6, 9 and 12 months

Study Arms (4)

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

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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
• 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.

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Respiratory Tract Infections; Olfaction Disorders; Influenza, Human; Rhinosinusitis; COVID-19; Depression; Anosmia

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Rhinitis; Sinusitis; Paranasal Sinus Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Lung Diseases; Behavioral Symptoms; Behavior

Study Officials

• Joshua M Levy, M.D.

  National Institute on Deafness and Other Communication Disorders (NIDCD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna E Clements Centeno

CONTACT

(301) 451-1215; anna.clements@nih.gov

Joshua M Levy, M.D.

CONTACT

(240) 935-8305; joshua.levy@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: September 2, 2025
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): October 14, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-03-25

Locations

US (1)