Olfactory Biopsies

NCT ID: NCT07021040

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-06
• Study Completion Date: 2028-12-31

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.

Detailed Description

The purpose of this study is to analyze cell populations active in human olfactory tissue in health and disease. This is a prospective study. Healthy participants or participants with known disease processes that may impact olfaction, such as Alzheimer's, inflammatory conditions, aging, or post-viral smell loss, will be included. Olfaction will be measured using standard psychophysical testing. Biopsies of the olfactory lining in the nasal cavity may be obtained in the otolaryngology clinic or the operating room, if the patient is having an unrelated endoscopic nasal surgery, and may be obtained using a punch technique or a cytology brush. Before biopsies, some patients may be asked to sniff an odor substance (such as lavender, mint, citrus, or cloves) briefly, to stimulate olfactory cells. Biopsies will be processed for assays in the PI's lab, including histology, primary culture assays, flow cytometry assays, or transcriptomic profiling.

Conditions

Alzheimer Disease; Smell Loss; Smell Dysfunction

Study Design

• Allocation Method: NA
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Alzheimer's study

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.

Group Type: OTHER

olfactory testing

Intervention Type: 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.

Odor stimulation

Intervention Type: 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.

Olfactory biopsy

Intervention Type: 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

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.

Group Type: OTHER

olfactory testing

Intervention Type: 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.

Odor stimulation

Intervention Type: 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.

Olfactory biopsy

Intervention Type: 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.

Interventions

olfactory testing

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.

Intervention Type: DIAGNOSTIC_TEST

Odor stimulation

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.

Intervention Type: OTHER

Olfactory biopsy

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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)

• Age 18 years or older
• Patients being seen for rhinology or olfactory disorders
• Patients having unrelated endoscopic nasal surgery

Exclusion Criteria

• 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

• 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
• Unable to provide legally effective consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Deafness and Other Communication Disorders (NIDCD)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bradley Goldstein, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Health Center

Durham, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Maria J Manson, MBA

Role: CONTACT

maria.manson@duke.edu

(919) 684-0525

Bradley J Goldstein, MD, PhD

Role: CONTACT

bradley.goldstein@duke.edu

(919) 684 3834

Facility Contacts

Bradley J Goldstein, MD

Role: primary

bradley.goldstein@duke.edu

919-684-3834

Maria J Manson, MBA

Role: backup

maria.manson@duke.edu

(919)684-0625

Other Identifiers

1R01DC021422-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00116591

Identifier Type: -

Identifier Source: org_study_id