Olfactory Biopsies

NCT07021040 | Recruiting

• 2 other identifiers: Pro001165911R01DC021422-01A1
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

This research study aims to investigate the function of the olfactory lining in the nasal cavity and its potential alterations in both healthy and diseased conditions. The olfactory lining is involved in the sense of smell. The purpose of this study is to collect tissue from the nasal cavity.

Conditions

Alzheimer Disease; Smell Loss; Smell Dysfunction

Keywords

act-seq; nasal biopsy; RNA-seq

Outcome Measures

Primary Outcomes (1)

• Transcription state changes in olfactory cells

  Using single cell RNA-sequencing, olfactory epithelial cell populations will be analyzed for changes in coherent gene expression programs from subjects in different environmental conditions.

  study is planned for completion over 5 years

Study Arms (2)

Alzheimer's study

OTHER

Olfactory function will be assessed using the Smell Identification Test (SIT, Sensonics, Inc) or Sniffin' Sticks Test. Using topical intranasal decongestion/anesthetic (oxymetazoline/lidocaine), a cytology brush biopsy will be obtained from the olfactory cleft region of the nose in clinic exam room using a nasal endoscope.

Diagnostic Test: olfactory testing; Other: Odor stimulation; Procedure: Olfactory biopsy

Act-seq study or Non-AD controls

OTHER

Olfactory function will be measured using established psychophysical testing via the Smell Identification Test or Sniffin' Sticks. Researchers will obtain biopsies from (1) normosmic subjects with or without odor stimulation, and (2) hyposmic subjects with history of upper respiratory infection (URI) as likely cause of the smell loss (such as COVID19) with or without odor stimulation.

Diagnostic Test: olfactory testing; Other: Odor stimulation; Procedure: Olfactory biopsy

Interventions

olfactory testing DIAGNOSTIC_TEST

Patients will undergo smell testing, using the Smell Identification Test (Sensonics), a validated widely-used 40-item "scratch-and-sniff" style psychophysical test to determine olfactory function.

Act-seq study or Non-AD controls; Alzheimer's study

Odor stimulation OTHER

subset of patients will be asked to sniff a specific odor for about an hour, using commercially available "odor pens" (Sniffin' Sticks or Sensonics). These odor pens are widely used for olfactory training therapy, a treatment designed to help people with some forms of smell loss; they are also used in psychophysical olfactory testing.

Act-seq study or Non-AD controls; Alzheimer's study

Olfactory biopsy PROCEDURE

Biopsy involves a simple cytology brush technique of the lining of the nose in a region called the olfactory cleft, using a nasal endoscope, and can be done in clinic or in the operating room at the time of a nasal surgery. Topical oxymetazoline and tetracaine spray is applied to the nasal cavity, a rigid nasal endoscopy (0-degree 4 mm endoscope, Karl Storz) is performed to visualize the olfactory cleft, and a small nasal cytology brush biopsy (Hobbs Medical)is performed by swabbing and rotating brush gently in the olfactory cleft. Cytology sample is placed into a buffer (Hibernate-E, Thermo Fisher)on ice for transport to the research lab.

Act-seq study or Non-AD controls; Alzheimer's study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 18 and 80
• Pre-clinical AD (this cohort consists of subjects who have normal cognitive testing and function, but have positive AD biomarkers);
• Symptomatic AD (a confirmed diagnosis of Alzheimer's or dementia who are capable of understanding and signing the consent document)

You may not qualify if:

• Advanced Alzheimer's/dementia
• Self-reported or known allergy to Afrin or Tetracain HCL (or related class of drugs)
• Active Rhinosinusitis symptoms
• Other known sinonasal disease history that would preclude biopsy (i.e prior sinus or skull base surgery directly impacting this anatomic region, sinonasal neoplasm in this anatomic region, olfactory cleft polyps)
• Parkinson's disease
• Unable or willing to complete the nasal endoscopy procedure.
• Unable to read or speak English
• Unable to provide legally effective consent
• Group 2: Act-seq study or Non-AD controls
• Age 18 years or older
• Patients being seen for rhinology or olfactory disorders
• Patients having unrelated endoscopic nasal surgery
• Self-reported or known allergy to Afrin or Tetracain HCL (or related class of drugs)
• Unable or willing to complete the nasal endoscopy procedure
• Unable to read or speak English

Sponsors & Collaborators

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

Study Sites (1)

Duke University Health Center

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Anosmia; Olfaction Disorders

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Bradley Goldstein, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria J Manson, MBA

CONTACT

(919) 684-0525; maria.manson@duke.edu

Bradley J Goldstein, MD, PhD

CONTACT

(919) 684 3834; bradley.goldstein@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 13, 2025
• Study Start: January 6, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)