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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04703595
Other study ID # IIBSP-TOS-2020-143
Secondary ID
Status Completed
Phase
First received
Last updated
Start date January 1, 2022
Est. completion date September 30, 2023

Study information

Verified date July 2022
Source Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

Chronic cough is a frequent cause of Pneumology consultations. CANVAS syndrome (Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome) is a progressive and disabling neurological disease that very frequently occurs with chronic cough. This cough invariably appears as a prodromal symptom that precedes neurological symptoms. The biallelic expansion of AAGGG in RFC1, a causal mutation in CANVAS syndrome, appears with high frequency in the general population. Objectives: Main: To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms. Secondary: Describe the phenotypic, functional and inflammatory characteristics of these patients. and Know the relationship between gastroesophageal reflux and chronic cough in patients with CANVAS. Method: A descriptive cross-sectional pilot study including 50 non-smoking patients between the ages of 30 and 99 years with chronic and / or refractory cough as the only manifestation or associated with gastroesophageal reflux. All patients will undergo the pertinent studies for the diagnosis of chronic cough, those who meet criteria for suspicion of gastroesophageal reflux will be requested an esophageal phmetry and esophageal manometry. Peripheral venous blood sample will be obtained for subsequent genetic analysis. Vibration sensitivity will be studied in all patients regardless of the presence of mutation. Those with alterations in vibratory sensitivity or mutations in RFC1 will be referred to the Neurology Service for a complementary neurological evaluation. For the molecular study of the DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification using Repeated Primed Polymerase chain reaction in 3 independent reactions.


Description:

A descriptive cross-sectional pilot study that included 50 non-smoking patients between the ages of 30 and 99 years with chronic and / or refractory cough as the only manifestation or associated with gastroesophageal reflux. All patients will undergo the pertinent studies for the diagnosis of chronic cough, those who meet criteria for suspected gastroesophageal reflux will be asked for an esophageal phmetry and esophageal manometry, according to the usual clinical practice. Peripheral venous blood sample will be obtained for subsequent genetic analysis. Vibration sensitivity will be studied in all patients regardless of the presence of mutation. Those with alterations in vibratory sensitivity or mutations in RFC1 will be referred to the Neurology Service for a complementary neurological evaluation. For the molecular study of the DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification using Repeated Primed Polymerase chain reaction in 3 independent reactions.


Recruitment information / eligibility

Status Completed
Enrollment 50
Est. completion date September 30, 2023
Est. primary completion date June 30, 2023
Accepts healthy volunteers No
Gender All
Age group 30 Years to 99 Years
Eligibility Inclusion Criteria: - Non-smokers - Aged between 30 and 99 years - with chronic and / or refractory cough as the only manifestation or associated with gastroesophageal reflux, who have signed the informed consent will be included. Exclusion Criteria: - Other causes of cough other than gastroesophageal reflux: pneumological diseases (asthma, Chronic obstructive pulmonary disease, bronchiectasis, tracheomalacia, cystic fibrosis, residual pleural diseases, interstitial diseases, infectious diseases.) - Upper airway pathologies (rhinitis, sinusitis) - Foreign bodies - Smokers or ex-smokers - Symptoms of associated respiratory allergies - Severe associated comorbidity. - Autoimmune disease or systemic inflammatory disease. - Active immunodeficiency. - Neoplastic disease.

Study Design


Intervention

Genetic:
To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms. For the molecular study of the DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification using Repeated Primed Polymerase chain reaction in 3 independent reactions.

Locations

Country Name City State
Spain Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90. Barcelona

Sponsors (1)

Lead Sponsor Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, Ilyas M, Tribollet E, Tomaselli PJ, Devigili G, Callegari I, Versino M, Salpietro V, Efthymiou S, Kaski D, Wood NW, Andrade NS, Buglo E, Rebelo A, Rossor AM, Bronstein A, Fratta P, Marques WJ, Zuchner S, Reilly MM, Houlden H. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet. 2019 Apr;51(4):649-658. doi: 10.1038/s41588-019-0372-4. Epub 2019 Mar 29. Erratum In: Nat Genet. 2019 May;51(5):920. — View Citation

Infante J, Garcia A, Serrano-Cardenas KM, Gonzalez-Aguado R, Gazulla J, de Lucas EM, Berciano J. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres. J Neurol. 2018 Jun;265(6):1454-1462. doi: 10.1007/s00415-018-8872-1. Epub 2018 Apr 25. — View Citation

Scriba CK, Beecroft SJ, Clayton JS, Cortese A, Sullivan R, Yau WY, Dominik N, Rodrigues M, Walker E, Dyer Z, Wu TY, Davis MR, Chandler DC, Weisburd B, Houlden H, Reilly MM, Laing NG, Lamont PJ, Roxburgh RH, Ravenscroft G. A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. Brain. 2020 Oct 1;143(10):2904-2910. doi: 10.1093/brain/awaa263. Erratum In: Brain. 2021 Jun 22;144(5):e51. — View Citation

Szmulewicz DJ, McLean CA, MacDougall HG, Roberts L, Storey E, Halmagyi GM. CANVAS an update: clinical presentation, investigation and management. J Vestib Res. 2014;24(5-6):465-74. doi: 10.3233/VES-140536. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms Study of the DNA sample of the patients with two techniques: standard Polymerase chain reaction amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification using Repeated Primed Polymerase chain reaction in 3 independent reactions. 6 months
Secondary Phenotypic, functional and inflammatory characteristics of these patients The tests of the usual clinical practice will be carried out for the study of chronic cough 12 months
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