CoughCANVASNCT04703595
Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)
An observational study of Cough and Cerebellar Ataxia, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 30 to 99 years
- Conditions the study is for
- Cough, Cerebellar Ataxia, Gastroesophageal Reflux
- What is being tested?
- To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2022to 30 Sep 2023
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- Autoimmune disease or systemic inflammatory disease.
- Active immunodeficiency.
- Neoplastic disease.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital de la Santa Creu i Sant Pau. Carrer Mas Casanovas 90.
Barcelona, 08041
About this study
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
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.
Read the 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.
- Conditions
- Cough, Cerebellar Ataxia, Gastroesophageal Reflux
- Being tested
- To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
- Keywords
- Cerebellar Ataxia, chronic cough, CANVAS
- Medical subject headings
- Cough, Cerebellar Ataxia, Gastroesophageal Reflux, Chronic Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Genetic: To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2021
- Study start1 Jan 2022
- Primary completion30 Jun 2023
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CoughStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Astrid Crespo, MD,PhD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04703595
- Sponsor's protocol ID
- IIBSP-TOS-2020-143
- Acronym
- CANVAS
- Status last verified
- Jul 2022
- First submitted
- 5 Jan 2021
- Last updated
- 20 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: * 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).
Publications
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.
PubMed 29696497Szmulewicz 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.
PubMed 25564090Scriba 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.
PubMed 33103729Cortese 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.
PubMed 30926972
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04703595
- Acronym / sponsor ID
- CANVAS / IIBSP-TOS-2020-143
- Conditions
- Cough, Cerebellar Ataxia, Gastroesophageal Reflux
- Keywords
- Cerebellar Ataxia, chronic cough, CANVAS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 11 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 12 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 50 non-smoking patients with chronic cough | – | Genetic: To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.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 |
Who may qualify
- Ages
- 30 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Genetic | 50 non-smoking patients with chronic cough |
Primary outcome
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.
1 secondary outcome
Phenotypic, functional and inflammatory characteristics of these patients
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2023.
- Background: PubMed 29696497Infante 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.
- Background: PubMed 25564090Szmulewicz 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.
- Background: PubMed 33103729Scriba 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.
- Background: PubMed 30926972Cortese 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.
- Individual participant dataSharing planned: No. * 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Astrid Crespo, MD,PhD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cough and Cerebellar Ataxia, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04703595, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2023.