Olfactory Biopsies for Loss of Smell

Overseen By Bradley J Goldstein, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Afrin, Tetracain

Disqualifiers: Advanced Alzheimer's, Parkinson's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the olfactory lining in the nose functions and changes under various conditions. Researchers collect nasal tissue samples (olfactory biopsy) to gain insights into smell, especially in individuals with Alzheimer's and those with smell disorders. Individuals with Alzheimer's or a history of smell loss after an infection, such as COVID-19, may be suitable for this study. Participants should not have allergies to specific medications used during the procedure or active sinus problems. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on smell disorders and Alzheimer's.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that olfactory biopsies are safe?

Research has shown that taking a small tissue sample from the nose, known as an olfactory biopsy, is generally safe. Studies have found that this procedure does not affect a person's sense of smell. Specifically, one study found that individuals who underwent the biopsy had similar nasal function and smell as those who did not.

Some minor side effects have been reported, but they usually resolve quickly. For example, individuals might experience a brief backache or mild headache after the procedure. Overall, these studies suggest that the procedure is well-tolerated and does not negatively impact quality of life. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel method for diagnosing and understanding the loss of smell, especially in conditions like Alzheimer's and post-viral smell loss (such as COVID-19). Unlike traditional tests that only assess smell function, this method involves taking a small biopsy from the olfactory region of the nose using a nasal endoscope. This approach could provide deeper insights into the cellular changes associated with smell loss, potentially leading to better-targeted treatments in the future. By comparing groups with different causes of smell loss, the study aims to uncover unique patterns that could differentiate between types of smell dysfunction. This could pave the way for more personalized diagnostic and treatment strategies.

What evidence suggests that olfactory biopsies are effective for assessing loss of smell?

Research shows that taking small tissue samples from the nose can help researchers understand smell disorders. In past studies, samples from the part of the nose that detects smells have provided important information. The success rate for collecting this tissue ranges from 40% to 89%, demonstrating the feasibility of gathering and studying it. In this trial, participants will undergo olfactory biopsies to explore the causes and potential treatments for smell loss. People who lost their sense of smell due to upper respiratory infections like COVID-19 generally experience higher recovery rates compared to other causes. This suggests that this method could offer valuable insights into how smell loss occurs and how it might be treated. ^{6 7 8 9 10}

Who Is on the Research Team?

Bradley Goldstein, MD, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's Disease, Parosmia (distorted smell perception), or Anomia (difficulty naming odors). It involves those who have lost their sense of smell. Participants must be healthy enough to undergo a biopsy.

Inclusion Criteria

Patients being seen for rhinology or olfactory disorders

I am between 18 and 80 years old.

Pre-clinical AD (subjects with normal cognitive testing and function, but positive AD biomarkers)

Exclusion Criteria

Self-reported or known allergy to Afrin or Tetracain HCL (or related class of drugs)

I am unable to give legal consent by myself.

Alzheimer's study:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Olfactory Function Assessment

Olfactory function is assessed using psychophysical testing such as the Smell Identification Test or Sniffin' Sticks Test

1-2 weeks

1 visit (in-person)

Biopsy Collection

Biopsies of the olfactory lining are obtained using a cytology brush or punch technique, potentially with odor stimulation

1 week

1 visit (in-person)

Analysis

Biopsies are processed for assays including histology, primary culture assays, flow cytometry assays, or transcriptomic profiling

Ongoing

Follow-up

Participants are monitored for any adverse effects post-biopsy and for data collection purposes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olfactory Biopsy

Trial Overview

The study is testing how the olfactory lining in the nasal cavity functions by using odor stimulation and olfactory testing. Researchers will collect tissue samples from participants' nasal cavities to examine potential changes due to health conditions.

How Is the Trial Designed?

Group I: Alzheimer's study Experimental Treatment 3 Interventions

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 II: Act-seq study or Non-AD controls Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9707095/

Investigations and Outcomes for Olfactory Disorders - PMC

This review highlights the key investigations and reasoning for their use to clinically assess and research patients with olfactory disorders.

2.

nature.com

nature.com/articles/s41598-023-41395-9

Remote psychophysical testing of smell in patients with ...

Using the OMT, impaired smell ability was detected in the vast majority of participants who contracted COVID-19. Persistent hyposmia or anosmia ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0196070921000909

Outcomes of olfaction in patients with empty nose ...

In conclusion, surgical treatment is effective in improving olfaction in patients with ENS, in which olfactory dysfunction is a significant characteristic.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9483995/

Biopsy of the olfactory epithelium from the superior nasal ...

The success rates of obtaining OE in biopsies performed from the nasal septum vary between 40% to 89%.9, 10, 11, 12, 13, 14, 15 However, these ...

5.

jamanetwork.com

jamanetwork.com/journals/jamaotolaryngology/fullarticle/482893

Characteristics of Olfactory Disorders in Relation to Major ...

Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/27107010/

Safety of human olfactory mucosal biopsy for the purpose ...

All Olfactory function outcomes were unaffected following olfactory biopsy. We demonstrated that the patients quality of life and nasal patency as well as ...

7.

researchgate.net

researchgate.net/figure/The-observed-adverse-events-following-the-olfactory-mucosa-biopsy-and-cell_tbl1_363440685

The observed adverse events following the olfactory ...

The most common adverse events were transient backache and meningism (90%) and cord malacia (80%). The cell therapy method in which the treatment was associated ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0385814622002401

Drug-induced olfactory and gustatory dysfunction

Recently, in 2021, the FDA identified duloxetine (Cymblata) as having potential serious risks of anosmia and hyposmia, and further evaluation of regulatory ...

9.

scispace.com

scispace.com/pdf/safety-of-human-olfactory-mucosal-biopsy-for-the-purpose-of-21akkoyal5.pdf

Safety of human olfactory mucosal biopsy for the purpose

Current evidence suggests that human olfactory mucosal biopsies do not have a detrimental effect on the patient's sense of smell (5,6), however ...

10.

discovery.ucl.ac.uk

discovery.ucl.ac.uk/1530783/

A prospective, controlled study on 131 patients assessing ...

The complication rate, the nasal function and the sense of smell outcomes of the biopsy group were statistically the same when compared to the control group. In ...