Ignite Creation Date:
2025-12-24 @ 1:37 PM
Ignite Modification Date:
2026-01-11 @ 6:55 AM
Study NCT ID:
NCT04703595
Status:
COMPLETED
Last Update Posted:
2023-12-20
First Post:
2021-01-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003371', 'term': 'Cough'}, {'id': 'D002524', 'term': 'Cerebellar Ataxia'}, {'id': 'D005764', 'term': 'Gastroesophageal Reflux'}, {'id': 'D000096822', 'term': 'Chronic Cough'}], 'ancestors': [{'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D002526', 'term': 'Cerebellar Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D001259', 'term': 'Ataxia'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D015154', 'term': 'Esophageal Motility Disorders'}, {'id': 'D003680', 'term': 'Deglutition Disorders'}, {'id': 'D004935', 'term': 'Esophageal Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': '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.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 50}, 'targetDuration': '12 Months', 'patientRegistry': True}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-07', 'completionDateStruct': {'date': '2023-09-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-12-19', 'studyFirstSubmitDate': '2021-01-05', 'studyFirstSubmitQcDate': '2021-01-08', 'lastUpdatePostDateStruct': {'date': '2023-12-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-01-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms', 'timeFrame': '6 months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Phenotypic, functional and inflammatory characteristics of these patients', 'timeFrame': '12 months', 'description': 'The tests of the usual clinical practice will be carried out for the study of chronic cough'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Cerebellar Ataxia', 'chronic cough', 'CANVAS'], 'conditions': ['Cough', 'Cerebellar Ataxia', 'Gastroesophageal Reflux']}, 'referencesModule': {'references': [{'pmid': '29696497', 'type': 'BACKGROUND', '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.'}, {'pmid': '25564090', 'type': 'BACKGROUND', '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.'}, {'pmid': '33103729', 'type': 'BACKGROUND', '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.'}, {'pmid': '30926972', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nAll 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.\n\nPeripheral venous blood sample will be obtained for subsequent genetic analysis.\n\nVibration sensitivity will be studied in all patients regardless of the presence of mutation.\n\nThose 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '30 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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.\n\nChronic 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.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Non-smokers\n* Aged between 30 and 99 years\n* with chronic and / or refractory cough as the only manifestation or associated with gastroesophageal reflux, who have signed the informed consent will be included.\n\nExclusion Criteria:\n\n* 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.)\n* Upper airway pathologies (rhinitis, sinusitis)\n* Foreign bodies\n* Smokers or ex-smokers\n* Symptoms of associated respiratory allergies\n* Severe associated comorbidity.\n* Autoimmune disease or systemic inflammatory disease.\n* Active immunodeficiency.\n* Neoplastic disease.'}, 'identificationModule': {'nctId': 'NCT04703595', 'acronym': 'CANVAS', 'briefTitle': 'Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)', 'organization': {'class': 'OTHER', 'fullName': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau"}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'IIBSP-TOS-2020-143'}}, 'armsInterventionsModule': {'armGroups': [{'label': '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', 'interventionNames': ['Genetic: To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.']}], 'interventions': [{'name': 'To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.', 'type': 'GENETIC', 'description': 'To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.\n\nFor 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.', 'armGroupLabels': ['50 non-smoking patients with chronic cough']}]}, 'contactsLocationsModule': {'locations': [{'zip': '08041', 'city': 'Barcelona', 'country': 'Spain', 'facility': 'Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}], 'overallOfficials': [{'name': 'Astrid Crespo, MD,PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', '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.\n* 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.\n* 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)\n* Period of interpretation of the results and writing of memory: for the publication of the results (December 2023 to June 2024)."}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau", 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}