Migraine With AuraPFOCUSNCT07349004
Neurogenetic And Hemodynamic Of Migraine Aura And Pfo
An observational study of Migraine With Aura, run by Azienda Usl di Bologna at 1 site in Italy.
Trial summary
The PFOCUS Study aims to clarify the relationship between patent foramen ovale (PFO) and migraine with aura (MA). Patients diagnosed with MA according to ICHD-3 criteria will be classified as cases (PFO+) or controls (PFO-) based on the presence or absence of a right-to-left shunt detected by transcranial Doppler or a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Migraine With Aura
- What is being tested?
- Intervention
- How many people
- 240 participants
- Where
- 1 siteItaly
- Study dates
- 24 Nov 2025to Nov 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: primary care clinic
Who may be able to join
- Diagnosis of migraine with aura (according to Chapter 1.2 of the International Classification of Headache Disorders, 3rd edition [ICHD-3])
- Age ≥ 18 years
- Both sexes
- Obtained written informed consent to participate in the study
Who cannot join
- History of congenital heart disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Istituto delle Scienze Neurologiche di Bologna - AUSL of Bologna
Bologna, BO, 40139
Matteo Paolucci, +390513172087, matteo.paolucci@ausl.bologna.it
Andrea Zini, +390516478810, a.zini@ausl.bologna.it
About this study
Official title: Association Between PFO and Migraine With Aura: A Case-Control Observational Study With Genetic and Neurosonological Analysis
The PFOCUS Study aims to clarify the relationship between patent foramen ovale (PFO) and migraine with aura (MA). Patients diagnosed with MA according to ICHD-3 criteria will be classified as cases (PFO+) or controls (PFO-) based on the presence or absence of a right-to-left shunt detected by transcranial Doppler or a previously documented PFO. The study will enroll 240 adult participants over 36 months.
The primary objective is to determine whether genetic variants differ significantly between patients with MA with and without PFO. Secondary objectives include assessing cerebral blood flow regulation and platelet function in patients with MA with and without PFO.
Read more
Participants will undergo a single study visit including the collection of demographic and clinical data and a comprehensive neurosonological assessment. This will include microembolic signal counts, cerebrovascular reactivity testing, and a contrast-enhanced transcranial Doppler study for shunt detection. Blood samples will be collected for whole-exome sequencing (with a focus on NOTCH3 and an expanded gene panel) and for platelet aggregometry.
The study is expected to provide new insights into the biological mechanisms linking PFO and MA-potentially involving endothelial dysfunction, altered vascular smooth muscle responses, or platelet activation-thereby informing prevention strategies and guiding future research.
Read the detailed description
The PFOCUS study is a prospective, case-control observational investigation designed to explore the biological, vascular, and genetic factors associated with the coexistence of migraine with aura (MA) and patent foramen ovale (PFO). Epidemiological evidence indicates that individuals with MA have an increased risk of ischemic stroke even in the absence of traditional vascular risk factors. In parallel, a higher prevalence of PFO has been consistently reported in patients with MA, suggesting a potential role of PFO as a modifier of cerebrovascular risk. The mechanisms underlying this association are not fully understood and may involve factors beyond paradoxical embolism, including vascular dysfunction, altered cerebral hemodynamics, platelet activation, and genetic susceptibility.
The primary objective of the study is to compare the distribution of NOTCH3 gene variants and single nucleotide polymorphisms (SNPs) between patients with MA and PFO (PFO+) and patients with MA without PFO (PFO-). NOTCH3 encodes a receptor involved in vascular smooth muscle cell differentiation and small-vessel integrity, and pathogenic variants are known to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Variants in this gene have also been associated with migraine phenotypes and alterations in cerebral small-vessel function. Given the role of NOTCH signaling pathways in cardiac septation and closure of the fetal foramen ovale, genetic variation in this pathway may contribute to both MA susceptibility and persistence of PFO.
Secondary objectives include: (1) assessing variants and SNPs in additional genes involved in NOTCH signaling, cardiac development, vascular regulation, and PFO heritability; (2) evaluating the relationship between genetic variants and the degree of right-to-left shunt; (3) comparing microembolic signals (MES) between PFO+ and PFO- participants using automated transcranial Doppler detection; (4) assessing cerebrovascular reactivity (CVR) and dynamic cerebral autoregulation (dCA) using standardized neurosonological protocols; and (5) comparing platelet function profiles between groups.
Each participant will undergo a single study visit. Data collection will include a structured clinical and demographic assessment, detailed characterization of migraine phenotype (including aura characteristics, attack frequency, and coexistence of migraine without aura), and review of available brain magnetic resonance imaging (MRI) findings when available. The neurosonological assessment will include continuous transcranial Doppler monitoring for MES detection, evaluation of CVR using breath-hold and hyperventilation maneuvers, and assessment of cerebral autoregulation using transfer function analysis, as well as contrast-enhanced detection of right-to-left shunt using agitated saline. Peripheral blood samples will be collected for genetic analysis and platelet function testing. Whole-exome sequencing will be performed, with subsequent analyses focused on a predefined panel of genes, including but not limited to NOTCH3, NOTCH1, JAG1, and HTRA1. Platelet aggregation studies will be conducted using standardized laboratory methods.
The planned sample size is 240 participants, equally distributed between the PFO+ and PFO- groups. This sample size is based on the expected prevalence of NOTCH3 SNPs and the anticipated between-group differences. Statistical analyses will include comparisons of allele and genotype frequencies, assessment of Hardy-Weinberg equilibrium, linkage disequilibrium analyses, and multivariable comparisons of neurosonological and platelet function parameters.
By integrating genetic, neurosonological, and hematological data, the PFOCUS study aims to characterize potential biological differences between patients with MA with and without PFO and to contribute to a better understanding of migraine-related vascular vulnerability.
- Conditions
- Migraine With Aura
- Being tested
- Intervention
- Keywords
- patent foramen ovale, migraine with aura, CADASIL
- Medical subject headings
- Migraine with Aura, Foramen Ovale, Patent, CADASIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InterventionOther
Neurosonological protocol with continuous Doppler monitoring for microemboli detection, cerebrovascular reactivity and dynamic cerebral autoregulation testing, and a contrast-enhanced shunt study using agitated saline; blood samples for whole-exome sequencing and platelet aggregation studies.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Patients with migraine with aura who have a patent foramen ovale (MAPFO+) Receives: Other: Intervention | |
| Arm 2 | Patients with migraine with aura without patent foramen ovale (MAPFO-) Receives: Other: Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of number of NOTCH3 genetic variants
To evaluate whether significant differences exist in the frequency of NOTCH3 genetic variants between patients with migraine with aura who have a patent foramen ovale (PFO+) and those without (PFO-). Min=0, max undefined.
Measured: T0 (day 1)
Secondary outcomes (5)
Comparison of number of genetic variants in other selected genes
To evaluate whether significant differences exist in the frequency of genetic variants in other selected genes between patients with migraine with aura who have a patent foramen ovale (PFO+) and those without (PFO-). Min=0, max undefined.
Measured: T0 (day 1)
Correlation of genetic variants with shunt size
To assess whether the frequency of detected variants and SNPs correlates with the size of the right-to-left shunt in the PFO+ group (present vs absent).
Measured: T0 (day 1)
Comparison in number of spontaneous microeboli
To evaluate differences in the number of cerebral microemboli between PFO+ and PFO- patients. Min=0, max undefined.
Measured: T0 (day 1)
Comparison in cerebrovascular reactivity between PFO+ and PFO- patients
Evaluation of phase shift, gain and coherence for very low, low and high frequency obtained from Transfer function analysis (significant group difference: yes vs no)
Measured: T0 (day 1)
Differences in platelet function profiles between PFO+ and PFO- patients
Evaluation of ASPI-test and ADP-test values obtained from Multiplate® analyzer (significant group difference: yes vs no)
Measured: T0 (day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2026
- Study start24 Nov 2025
- Primary completion24 Nov 2025
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Migraine With AuraStudies of the same condition, open and under way.
- 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-control
- Time perspective
- Prospective
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Usl di Bologna
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Matteo Paolucci, Principal investigator, IRCCS Istituto delle Scienze Neurologiche di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07349004
- Sponsor's protocol ID
- PFOCUS
- Acronym
- PFOCUS
- Status last verified
- Feb 2026
- First submitted
- 9 Jan 2026
- Last updated
- 11 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
West BH, Noureddin N, Mamzhi Y, Low CG, Coluzzi AC, Shih EJ, Gevorgyan Fleming R, Saver JL, Liebeskind DS, Charles A, Tobis JM. Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke. Stroke. 2018 May;49(5):1123-1128. doi: 10.1161/STROKEAHA.117.020160. Epub 2018 Apr 10.
PubMed 29636424Trabattoni D, Brambilla M, Canzano P, Becchetti A, Teruzzi G, Porro B, Fiorelli S, Muratori M, Tedesco CC, Veglia F, Montorsi P, Bartorelli AL, Tremoli E, Camera M. Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study. JACC Basic Transl Sci. 2022 Apr 13;7(6):525-540. doi: 10.1016/j.jacbts.2022.02.002. eCollection 2022 Jun.
PubMed 35818509Takagi H, Umemoto T; ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A meta-analysis of case-control studies of the association of migraine and patent foramen ovale. J Cardiol. 2016 Jun;67(6):493-503. doi: 10.1016/j.jjcc.2015.09.016. Epub 2015 Oct 31.
PubMed 26527111Schwaag S, Evers S, Schirmacher A, Stogbauer F, Ringelstein EB, Kuhlenbaumer G. Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and association study. Cephalalgia. 2006 Feb;26(2):158-61. doi: 10.1111/j.1468-2982.2005.01007.x.
PubMed 16426270Schmidt H, Zeginigg M, Wiltgen M, Freudenberger P, Petrovic K, Cavalieri M, Gider P, Enzinger C, Fornage M, Debette S, Rotter JI, Ikram MA, Launer LJ, Schmidt R; CHARGE consortium Neurology working group. Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease. Brain. 2011 Nov;134(Pt 11):3384-97. doi: 10.1093/brain/awr252. Epub 2011 Oct 17.
PubMed 22006983Rutten JW, Dauwerse HG, Gravesteijn G, van Belzen MJ, van der Grond J, Polke JM, Bernal-Quiros M, Lesnik Oberstein SA. Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol. 2016 Sep 28;3(11):844-853. doi: 10.1002/acn3.344. eCollection 2016 Nov.
PubMed 27844030Paolucci M, Vincenzi C, Romoli M, Amico G, Ceccherini I, Lattanzi S, Bersano A, Longoni M, Sacco S, Vernieri F, Pascarella R, Valzania F, Zedde M. The Genetic Landscape of Patent Foramen Ovale: A Systematic Review. Genes (Basel). 2021 Dec 6;12(12):1953. doi: 10.3390/genes12121953.
PubMed 34946902Paolucci M, Altamura C, Vernieri F. The Role of Endothelial Dysfunction in the Pathophysiology and Cerebrovascular Effects of Migraine: A Narrative Review. J Clin Neurol. 2021 Apr;17(2):164-175. doi: 10.3988/jcn.2021.17.2.164.
PubMed 33835736van Os HJA, Mulder IA, Broersen A, Algra A, van der Schaaf IC, Kappelle LJ, Velthuis BK, Terwindt GM, Schonewille WJ, Visser MC, Ferrari MD, van Walderveen MAA, Wermer MJH; DUST Investigators. Migraine and Cerebrovascular Atherosclerosis in Patients With Ischemic Stroke. Stroke. 2017 Jul;48(7):1973-1975. doi: 10.1161/STROKEAHA.116.016133. Epub 2017 May 19.
PubMed 28526767Menon S, Cox HC, Kuwahata M, Quinlan S, MacMillan JC, Haupt LM, Lea RA, Griffiths LR. Association of a Notch 3 gene polymorphism with migraine susceptibility. Cephalalgia. 2011 Feb;31(3):264-70. doi: 10.1177/0333102410381143. Epub 2010 Sep 2.
PubMed 20813781Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002 Mar 26;58(6):885-94. doi: 10.1212/wnl.58.6.885.
PubMed 11914403Li X, Xie L, Dai J, Zhou X, Chen T, Mao W. A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders. Front Genet. 2024 May 14;15:1405307. doi: 10.3389/fgene.2024.1405307. eCollection 2024.
PubMed 38808331Lantz M, Sieurin J, Sjolander A, Waldenlind E, Sjostrand C, Wirdefeldt K. Migraine and risk of stroke: a national population-based twin study. Brain. 2017 Oct 1;140(10):2653-2662. doi: 10.1093/brain/awx223.
PubMed 28969391Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012 Jan;11(1):92-100. doi: 10.1016/S1474-4422(11)70266-6.
PubMed 22172624Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
PubMed 29368949
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between PFO and Migraine With Aura: A Case-Control Observational Study With Genetic and Neurosonological Analysis
- ClinicalTrials.gov ID
- NCT07349004
- Acronym / sponsor ID
- PFOCUS / PFOCUS
- Conditions
- Migraine With Aura
- Keywords
- patent foramen ovale, migraine with aura, CADASIL
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Azienda Usl di BolognaOther government
- Study start
- 24 Nov 2025 (actual)
- Primary completion
- 24 Nov 2025 (actual)
- Study completion
- Nov 2028 (estimated)
- First posted
- 16 Jan 2026 (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.
The PFOCUS Study aims to clarify the relationship between patent foramen ovale (PFO) and migraine with aura (MA). Patients diagnosed with MA according to ICHD-3 criteria will be classified as cases (PFO+) or controls (PFO-) based on the presence or absence of a right-to-left shunt detected by transcranial Doppler or a previously documented PFO. The study will enroll 240 adult participants over 36 months.
The primary objective is to determine whether genetic variants differ significantly between patients with MA with and without PFO. Secondary objectives include assessing cerebral blood flow regulation and platelet function in patients with MA with and without PFO.
Participants will undergo a single study visit including the collection of demographic and clinical data and a comprehensive neurosonological assessment. This will include microembolic signal counts, cerebrovascular reactivity testing, and a contrast-enhanced transcranial Doppler study for shunt detection. Blood samples will be collected for whole-exome sequencing (with a focus on NOTCH3 and an expanded gene panel) and for platelet aggregometry.
The study is expected to provide new insights into the biological mechanisms linking PFO and MA-potentially involving endothelial dysfunction, altered vascular smooth muscle responses, or platelet activation-thereby informing prevention strategies and guiding future research.
Detailed description
The PFOCUS study is a prospective, case-control observational investigation designed to explore the biological, vascular, and genetic factors associated with the coexistence of migraine with aura (MA) and patent foramen ovale (PFO). Epidemiological evidence indicates that individuals with MA have an increased risk of ischemic stroke even in the absence of traditional vascular risk factors. In parallel, a higher prevalence of PFO has been consistently reported in patients with MA, suggesting a potential role of PFO as a modifier of cerebrovascular risk. The mechanisms underlying this association are not fully understood and may involve factors beyond paradoxical embolism, including vascular dysfunction, altered cerebral hemodynamics, platelet activation, and genetic susceptibility.
The primary objective of the study is to compare the distribution of NOTCH3 gene variants and single nucleotide polymorphisms (SNPs) between patients with MA and PFO (PFO+) and patients with MA without PFO (PFO-). NOTCH3 encodes a receptor involved in vascular smooth muscle cell differentiation and small-vessel integrity, and pathogenic variants are known to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Variants in this gene have also been associated with migraine phenotypes and alterations in cerebral small-vessel function. Given the role of NOTCH signaling pathways in cardiac septation and closure of the fetal foramen ovale, genetic variation in this pathway may contribute to both MA susceptibility and persistence of PFO.
Secondary objectives include: (1) assessing variants and SNPs in additional genes involved in NOTCH signaling, cardiac development, vascular regulation, and PFO heritability; (2) evaluating the relationship between genetic variants and the degree of right-to-left shunt; (3) comparing microembolic signals (MES) between PFO+ and PFO- participants using automated transcranial Doppler detection; (4) assessing cerebrovascular reactivity (CVR) and dynamic cerebral autoregulation (dCA) using standardized neurosonological protocols; and (5) comparing platelet function profiles between groups.
Each participant will undergo a single study visit. Data collection will include a structured clinical and demographic assessment, detailed characterization of migraine phenotype (including aura characteristics, attack frequency, and coexistence of migraine without aura), and review of available brain magnetic resonance imaging (MRI) findings when available. The neurosonological assessment will include continuous transcranial Doppler monitoring for MES detection, evaluation of CVR using breath-hold and hyperventilation maneuvers, and assessment of cerebral autoregulation using transfer function analysis, as well as contrast-enhanced detection of right-to-left shunt using agitated saline. Peripheral blood samples will be collected for genetic analysis and platelet function testing. Whole-exome sequencing will be performed, with subsequent analyses focused on a predefined panel of genes, including but not limited to NOTCH3, NOTCH1, JAG1, and HTRA1. Platelet aggregation studies will be conducted using standardized laboratory methods.
The planned sample size is 240 participants, equally distributed between the PFO+ and PFO- groups. This sample size is based on the expected prevalence of NOTCH3 SNPs and the anticipated between-group differences. Statistical analyses will include comparisons of allele and genotype frequencies, assessment of Hardy-Weinberg equilibrium, linkage disequilibrium analyses, and multivariable comparisons of neurosonological and platelet function parameters.
By integrating genetic, neurosonological, and hematological data, the PFOCUS study aims to characterize potential biological differences between patients with MA with and without PFO and to contribute to a better understanding of migraine-related vascular vulnerability.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | – | Other: InterventionPatients with migraine with aura who have a patent foramen ovale (MAPFO+) |
| Arm 2 | – | Other: InterventionPatients with migraine with aura without patent foramen ovale (MAPFO-) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- primary care clinic
Key inclusion criteria (4 listed)
- Diagnosis of migraine with aura (according to Chapter 1.2 of the International Classification of Headache Disorders, 3rd edition [ICHD-3])
- Age ≥ 18 years
- Both sexes
- Obtained written informed consent to participate in the study
Key exclusion criteria (1 listed)
- History of congenital heart disease
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 |
|---|---|---|
| InterventionNeurosonological protocol with continuous Doppler monitoring for microemboli detection, cerebrovascular reactivity and dynamic cerebral autoregulation testing, and a contrast-enhanced shunt study using agitated saline; blood samples for whole-exome sequencing and platelet aggregation studies. | Other | Arm 1, Arm 2 |
Primary outcome
Comparison of number of NOTCH3 genetic variants
Time frame: T0 (day 1)
To evaluate whether significant differences exist in the frequency of NOTCH3 genetic variants between patients with migraine with aura who have a patent foramen ovale (PFO+) and those without (PFO-). Min=0, max undefined.
5 secondary outcomes
Comparison of number of genetic variants in other selected genes
Time frame: T0 (day 1)
Correlation of genetic variants with shunt size
Time frame: T0 (day 1)
Comparison in number of spontaneous microeboli
Time frame: T0 (day 1)
Comparison in cerebrovascular reactivity between PFO+ and PFO- patients
Time frame: T0 (day 1)
Differences in platelet function profiles between PFO+ and PFO- patients
Time frame: T0 (day 1)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2026.
- Background: PubMed 29636424West BH, Noureddin N, Mamzhi Y, Low CG, Coluzzi AC, Shih EJ, Gevorgyan Fleming R, Saver JL, Liebeskind DS, Charles A, Tobis JM. Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke. Stroke. 2018 May;49(5):1123-1128. doi: 10.1161/STROKEAHA.117.020160. Epub 2018 Apr 10.
- Background: PubMed 35818509Trabattoni D, Brambilla M, Canzano P, Becchetti A, Teruzzi G, Porro B, Fiorelli S, Muratori M, Tedesco CC, Veglia F, Montorsi P, Bartorelli AL, Tremoli E, Camera M. Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study. JACC Basic Transl Sci. 2022 Apr 13;7(6):525-540. doi: 10.1016/j.jacbts.2022.02.002. eCollection 2022 Jun.
- Background: PubMed 26527111Takagi H, Umemoto T; ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A meta-analysis of case-control studies of the association of migraine and patent foramen ovale. J Cardiol. 2016 Jun;67(6):493-503. doi: 10.1016/j.jjcc.2015.09.016. Epub 2015 Oct 31.
- Background: PubMed 16426270Schwaag S, Evers S, Schirmacher A, Stogbauer F, Ringelstein EB, Kuhlenbaumer G. Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and association study. Cephalalgia. 2006 Feb;26(2):158-61. doi: 10.1111/j.1468-2982.2005.01007.x.
- Background: PubMed 22006983Schmidt H, Zeginigg M, Wiltgen M, Freudenberger P, Petrovic K, Cavalieri M, Gider P, Enzinger C, Fornage M, Debette S, Rotter JI, Ikram MA, Launer LJ, Schmidt R; CHARGE consortium Neurology working group. Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease. Brain. 2011 Nov;134(Pt 11):3384-97. doi: 10.1093/brain/awr252. Epub 2011 Oct 17.
- Background: PubMed 27844030Rutten JW, Dauwerse HG, Gravesteijn G, van Belzen MJ, van der Grond J, Polke JM, Bernal-Quiros M, Lesnik Oberstein SA. Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol. 2016 Sep 28;3(11):844-853. doi: 10.1002/acn3.344. eCollection 2016 Nov.
- Background: PubMed 34946902Paolucci M, Vincenzi C, Romoli M, Amico G, Ceccherini I, Lattanzi S, Bersano A, Longoni M, Sacco S, Vernieri F, Pascarella R, Valzania F, Zedde M. The Genetic Landscape of Patent Foramen Ovale: A Systematic Review. Genes (Basel). 2021 Dec 6;12(12):1953. doi: 10.3390/genes12121953.
- Background: PubMed 33835736Paolucci M, Altamura C, Vernieri F. The Role of Endothelial Dysfunction in the Pathophysiology and Cerebrovascular Effects of Migraine: A Narrative Review. J Clin Neurol. 2021 Apr;17(2):164-175. doi: 10.3988/jcn.2021.17.2.164.
- Background: PubMed 28526767van Os HJA, Mulder IA, Broersen A, Algra A, van der Schaaf IC, Kappelle LJ, Velthuis BK, Terwindt GM, Schonewille WJ, Visser MC, Ferrari MD, van Walderveen MAA, Wermer MJH; DUST Investigators. Migraine and Cerebrovascular Atherosclerosis in Patients With Ischemic Stroke. Stroke. 2017 Jul;48(7):1973-1975. doi: 10.1161/STROKEAHA.116.016133. Epub 2017 May 19.
- Background: PubMed 20813781Menon S, Cox HC, Kuwahata M, Quinlan S, MacMillan JC, Haupt LM, Lea RA, Griffiths LR. Association of a Notch 3 gene polymorphism with migraine susceptibility. Cephalalgia. 2011 Feb;31(3):264-70. doi: 10.1177/0333102410381143. Epub 2010 Sep 2.
- Background: PubMed 11914403Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002 Mar 26;58(6):885-94. doi: 10.1212/wnl.58.6.885.
- Background: PubMed 38808331Li X, Xie L, Dai J, Zhou X, Chen T, Mao W. A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders. Front Genet. 2024 May 14;15:1405307. doi: 10.3389/fgene.2024.1405307. eCollection 2024.
- Individual participant dataSharing planned: No
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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.
Matteo Paolucci principal investigator
IRCCS Istituto delle Scienze Neurologiche di Bologna
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 Migraine With Aura, run by Azienda Usl di Bologna at 1 site in Italy.
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 4 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 11 Feb 2026. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matteo Paolucci (+390513172087, matteo.paolucci@ausl.bologna.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of number of NOTCH3 genetic variants (time frame: T0 (day 1)). 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 NCT07349004, which also lists 22 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 11 Feb 2026.