In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry

1. Assessment of a high speed video camera with a green light source for the measurement of ciliary beat frequency (CBF) in the nasal airways of patients.
2. Assessments of the effect of drugs and other therapies on CBF using the study system.
3. Comparison of results with standard methods such as ciliary brush biopsies

Study Overview

• Status: Unknown
• Conditions: Primary Ciliary Dyskinesia
• Intervention / Treatment: Device: CBF measurements

Detailed Description

Background Mucociliary clearance of the airways depends on ciliary movement by ciliated cells that cover the entire airway and the sinuses. In many airway diseases the mucociliary clearance is affected by injury caused by smoke, viruses, other infectious organisms or genetic diseases that are called Primary Ciliary Dyskinesia (PCD).

The diagnosis of PCD is based on a combination of clinical findings such as bronchiectasis, chronic sinusitis, chronic otitis media and immotile sperms.

In addition, in tests performed in the pulmonary laboratory nasal nitric oxide levels may be low.

Samples obtained by nasal brush biopsy can be analyzed and the ciliary movement recorded by video microscopy. Ciliary beat frequency (CBF) can be calculated in freshly isolated samples but also after growing the tissue in cell culture.

Furthermore, ciliated cells can be analyzed by electron microscopy to detect defects in the microscopic structure of the cilia.

The major problem encountered by all these assays is that they are performed under in vitro conditions and not in the natural environment of the cells where the acidity (pH), temperature, electrolytes etc. may be very different.

Moreover, genetic testing is limited to mutations known to cause PCD, ruling out mutations not yet discovered.

Therefore a method is needed to unequivocally measure ciliary movement in the natural environment.

Goal

1. Assessment of a high speed video camera with a green light source for the measurement of ciliary beat frequency (CBF) in the nasal airways of patients.
2. Assessments of the effect of drugs and other therapies on CBF using the study system.

Methods The protocol has been approved by the local Institutional Review Board (IRB) of the Hadassah Medical Center, Jerusalem, Israel

Equipment:

1. High Speed High Video Microscope built to specifications needed for this study based on a commercially available high speed video system.
2. The green light source (LED) used consists of a spot of 3mm diameter and has an energy of 10 milli Watt ( equal to 1Kilowatt/square meter)
3. Video camera (manufactured by SONY Inc, Japan)

Patients:

Patients referred for ciliary brush biopsy will be asked to sign the informed consent and to be enrolled into the study.

Patients will be examined by having a high speed digital video camera placed close to the nasal cavity in order to photograph the area of interest. The camera lens will be off focus and the reflected light from the nasal mucosa will be recorded. This reflected light recording will be analyzed to obtain the CBF, heart rate and respiratory rate.

After the recording the patient will proceed to the nasal brush ciliary biopsy. The cells will be analyzed by a CBF will be calculated from several areas of the smear.

Safety measures:

All participating patients will wear a protective cover over their eyes during photography.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: David Shoseyov, MD; Phone Number: 972-507874091; Email: shoseyov@hadassah.org.il

Study Locations

• Israel
  • Jerusalem, Israel, 91240
    • Hadassah Medical Organization
    • Contact: David Shoseyov, MD; Phone Number: 972-2-5844430/1; Email: shoseyov@hadassah.org.il
    • Sub-Investigator: Reuven Tzabari, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with suspected PCD

Description

Inclusion Criteria:

• Patients referred for Ciliary Brush Biopsy

Exclusion Criteria:

• Active nasal bleeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Suspected PCD but negative; CBF measurements: Patients with suspected PCD will have their nasal cavity photographed using a Sony-video camera that will record the reflected light of a green LED bulb.Ciliary beat frequency (CBF) will be calculated by interferometry using a program developed by the PI.; Patients will undergo a nasal brush biopsies. The fresh biopsies will be analyzed by high-speed video microscopy to calculate CBF.; The two methods will be compared.	Device: CBF measurements; CBF measurements; Other Names: Ciliary brush biopsy
Suspected PCD but positive; CBF measurements: Patients with suspected PCD will have their nasal cavity photographed using a Sony-video camera that will record the reflected light of a green LED bulb.Ciliary beat frequency (CBF) will be calculated by interferometry using a program developed by the PI.; Patients will undergo a nasal brush biopsies. The fresh biopsies will be analyzed by high-speed video microscopy to calculate CBF.; The two methods will be compared.	Device: CBF measurements; CBF measurements; Other Names: Ciliary brush biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ciliary beat frequency (CBF) measured by high speed video microscopy	Ex vivo measurements of CBF analysing high speed video records of nasal brush biopsies	5 minutes
Ciliary beat frequency (CBF) measured by interferometry	In vivo measurements of CBF analysing the reflected light from the nasal cavity	5 minutes

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: David Shoseyov, MD, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: February 29, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Estimate): March 4, 2016
• Last Update Submitted That Met QC Criteria: February 29, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: ciliary beat frequency,
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Movement Disorders; Abnormalities, Multiple; Ciliopathies; Dyskinesias; Ciliary Motility Disorders
• Other Study ID Numbers: 0366-15-HMO-CTIL

Plan for Individual participant data (IPD)

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