SOLFAMU Study of Nasal Brushing Collected OLFActory MUcosa Samples in the Diagnosis of Human Encephalopathies

Study of Nasal Brushing Collected OLFActory MUcosa Samples in the Diagnosis of Human Encephalopathies

Encephalopathies are a group of central nervous system (CNS) affection with heterogeneous etiology. Several causes have been recognized including neurodegenerative, vascular, infectious, autoimmune, toxic or allergic affections or secondary to systemic disorders. While 30-50% of acute encephalitis remains without etiological definition, definitive criteria for neurodegenerative diseases are usually unavailable in vivo and possible or probable definitions are used. The Olfactory mucosa (OM) is the part of the nasal mucosa that carries the specialized sensory organ for the modality of smell; the olfactory epithelium is composed of five principal cell types including olfactory receptor neurons. A sample of OM may be collected through a rhinoscopy-guided brushing: it is well-accepted by patients, not-contraindicated in patients with raised intracranial pressure and associated with almost no side-effects. Nasal brushing has recently been proposed for the in vivo diagnosis of Creutzfeldt-Jakob disease (CJD).

Aims of the project are:

1. Training of ear throat and nose (ETN), Infectious disease (ID) and neurology (NEU) specialists in the technique of nasal brushing;
2. Conducting a prospective study comparing the use of nasal brushing with gold-standard criteria in the diagnosis of Encephalopathies;
3. Increasing the diagnostic and prognostic power in the diagnosis of encephalopathies.

A prospective, case control, multicentric study enrolling 400 patients and 100 controls (patients with nasal stenosis undergoing rhinoscopy for clinical reasons). Patients will be diagnosed and followed according to international guidelines and local clinical practice. Cerebrospinal fluid and magnetic resonance imaging will be used, where indicated, for the diagnosis according to the clinical or radiological suspect.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Dementia; Encephalopathy; HIV-encephalopathy
• Intervention / Treatment: Device: Nasal Brushing

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: ANDREA CALCAGNO, MD, DTM&H; Phone Number: +390114393884; Email: andrea.calcagno@unito.it

Study Locations

• Italy
  • Torino, Italy
    • Recruiting
    • University of Torino
    • Contact: Andrea Calcagno, MD; Phone Number: +390114393884; Email: andrea.calcagno@unito.it
    • Sub-Investigator: Stefano Bonora, MD
    • Principal Investigator: Giovanni Di Perri, MD, PhD
    • Sub-Investigator: Andrea Calcagno, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for cases:

• age>18 years;
• signing a written informed consent (by the patients or his/her legal representant);
• clinical suspect of encephalopathy (acute or subacute) including acute encephalitis, neurodegenerative disorders and HIV-associated neurocognitive disorders.

Inclusion criteria for controls:

• age>18 years;
• signing a written informed consent (by the patients or his/her legal representant); • clinical indication for rhinoscopy for stenotic disease of nasal sept or turbinates.

Exclusion criteria:

• Nasal anatomical abnormalities precluding the execution of nasal brushing;
• Serious general conditions and/or comorbidities in patients for whom nasal brushing may be a risk factor precipitating their pre-existing condition;
• Anti-coagulant treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Brushing; Patients will undergo nasal brushing as further described additionally to other gold standard practices according to the suspected aetiology (brain MRI, lumbar puncture, plasma tests, etc.)

Device: Nasal Brushing; Nasal brushing will be performed in non-sedated patients as follows. After administration of a local vasoconstrictor (1% epinephrine) with the use of a nasal tampon, inserted into the nasal cavity of the patient to locate the olfactory mucosa lining the nasal vault. A sterile, disposable brush ("Copanflock", "Copan", Brescia, Italy) will be inserted gently rolled on the mucosal surface, withdrawn,and immersed in 0.9% saline solution, UTM (Universal Transporter Medium) or 4% formaldehyde. Two swabs will be collected for each nostril.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic concordance with gold standard diagnostic procedures	Positive and negative predictive values and correct classification rates of OM tests versus gold standard diagnostic procedures	Single-visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of the nasal brushing	Prevalence of side effects reported during the brushing and up to 6 months afterwards	Up to 6 months after the procedure
Cytological and immunohistochemistry examination of nasal brushing smear (neuronal abnormalities and expression of specific markers according to the different aetiologies)	Prevalence of samples showing: abnormalities in cytological examination, antiOMP (Olfactory Marker Protein) positive cells, white blood cells and subtypes.	single-visit
OM markers of neuronal damage and amyloid deposition	Quantification of tau, p-tau, 1-42 beta amyloid, S100beta, alpha synuclein, TDP-43 (TAR DNA-binding protein 43) on cell blocks and supernatant	single-visit

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Investigators: Principal Investigator: GIOVANNI DI PERRI, MD, PhD, University of Torino

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: October 28, 2016
• First Posted (Estimate): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; HIV Infections; Alzheimer Disease; Brain Diseases; AIDS Dementia Complex
• Other Study ID Numbers: SOLFAMU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No