Brief Title
Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)
Official Title
Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome): Screening for Mutations in Subunit 1 of the Replication Factor Complex: Initial Pilot Study
Brief 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.
Detailed 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.
Study Type
Observational [Patient Registry]
Primary Outcome
To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms
Secondary Outcome
Know the phenotypic, functional and inflammatory characteristics of these patients
Condition
Cough
Intervention
To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
Study Arms / Comparison Groups
50 non-smoking patients with chronic cough
Description: 50 non-smoking patients aged between 30 and 99 years with chronic and / or refractory cough as the only manifestation or associated with gastroesophageal reflux
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
50
Start Date
June 1, 2021
Completion Date
June 30, 2023
Primary Completion Date
June 30, 2022
Eligibility Criteria
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.
Gender
All
Ages
30 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Astrid Crespo, MD,PhD, +34-93 556 56 01, [email protected]
Administrative Informations
NCT ID
NCT04703595
Organization ID
IIBSP-TOS-2020-143
Responsible Party
Sponsor
Study Sponsor
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Study Sponsor
Astrid Crespo, MD,PhD, Principal Investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Verification Date
January 2021