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Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome) (CANVAS)

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ClinicalTrials.gov Identifier: NCT04703595
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : July 18, 2022
Sponsor:
Information provided by (Responsible Party):
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

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.

Condition or disease Intervention/treatment
Cough Cerebellar Ataxia Gastroesophageal Reflux Genetic: To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 50 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 12 Months
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
Actual Study Start Date : January 1, 2022
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : December 30, 2023


Group/Cohort Intervention/treatment
50 non-smoking patients with chronic cough
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
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.





Primary Outcome Measures :
  1. Presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. Phenotypic, functional and inflammatory characteristics of these patients [ Time Frame: 12 months ]
    The tests of the usual clinical practice will be carried out for the study of chronic cough


Biospecimen Retention:   Samples With DNA
For the molecular study of the DNA sample of the patients, two techniques will be used: amplification by standard Polymerase chain reaction with primers flanking the intron 2 fragment of the RFC1 gene and amplification by Repeated Primed Polymerase chain reaction in 3 independent reactions.


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

A total of 50 patients, 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.

Chronic cough will be defined as cough lasting more than 8 weeks that is not related to an acute (3 weeks) or subacute (3-8 weeks) process.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04703595


Contacts
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Contact: Astrid Crespo, MD,PhD +34-93 556 56 01 acrespo@santpau.cat
Contact: Claudia Delgado, MD +34-932919000 cdelgadoe@santpau.cat

Locations
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Spain
Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90. Recruiting
Barcelona, Spain, 08041
Contact: Astrid Crespo, MD    +34-935565972    acrespo@santpau.cat   
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Investigators
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Principal Investigator: Astrid Crespo, MD,PhD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Publications:

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Responsible Party: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier: NCT04703595    
Other Study ID Numbers: IIBSP-TOS-2020-143
First Posted: January 11, 2021    Key Record Dates
Last Update Posted: July 18, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:
  • Study design (from November 2020 to June 2021): In this phase, the protocol will be elaborated, the study materials will be edited, the database design will be carried out, meetings will be held with the researchers to resolve doubts The logistical aspects will be prepared for the start of the study and the project will be presented to the Hospital's ethics committee.
  • Recruitment period: one year (study start in June 2021): In this phase, patients will be identified, data will be collected and entered. This phase would end in June 2022.
  • Period of analysis of the genetic samples, purification and analysis of the data: this phase is calculated to be carried out in 6 months (June 2022 to December 2022)
  • Period of interpretation of the results and writing of memory: for the publication of the results (December 2023 to June 2024).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:
Cerebellar Ataxia
chronic cough
CANVAS
Additional relevant MeSH terms:
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Gastroesophageal Reflux
Cough
Bilateral Vestibulopathy
Ataxia
Cerebellar Ataxia
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Vestibular Diseases
Labyrinth Diseases
Ear Diseases
Otorhinolaryngologic Diseases