Precutaneous High Risk Patent Foramen Ovale to Treat Migraine Headaches

Precutaneous High Risk Patent Foramen Ovale to Treat Migraine Headaches:A Prospective,Multicenter,Randomized,Controlled Trial

The foramen ovale, a kind of physiologic channel in the interatrial septum in the heart at embryonic stage, is closed normally at 5-7 months after birth. When it is not closed, it is referred to as the patent foramen ovale (PFO), which is found in approximately 1/4 of general population. It was shown in the studies in recent years that the risks of cryptogenic stroke, migraine, peripheral arterial embolism and decompression sickness in the patients with PFO were several times higher than those in healthy people. Therefore, PFO, previously considered a condition without the necessity of treatment, causes the attention of many experts and scholars around the world. Migraine with or without aura is defined as one of the most disabling chronic diseases, since according to WHO, the disability adjusted life year caused by migraine was second only to that by non-fatal stroke in 2005. In recent years, an increasing number of researches suggested that migraine is closely related to the right-to-left shunt (RLS) in the heart. And PFO is clinically considered as the most common cause of RLS.

The closure treatment for PFO-induced migraine has been gradually applied in several hospitals in China. The relationship of PFO with migraine, however, was not evaluated systematically based on specific standards, unfortunately leading to non-inclusion of many high-risk patients with PFO in the evaluation. The following aspects are to be fully recognized: the selecting and screening procedures for the high-risk population with PFO-induced migraine; the indications and standards of closure treatment for PFO in the patients with PFO-induced migraine; and the possibility that the made-in-China occluders substitute for those imported in the prevention from migraine. Furthermore, there is still a lack of prospective, multi-center, randomized and controlled studies in this subject, and standard or normal screening and treatment procedures have not yet been established in China. From this point, the investigators developed the Chinese people-specific procedures and standards of diagnosis of PFO-induced migraine in this study, based on current standards and methods of diagnosis, treatment and prevention of PFO-induced migraine in foreign countries. And the investigators prospectively adopted continuous inclusion of the high-risk patients with PFO-induced migraine, who were randomly divided into the closure treatment (transcatheter closure of PFO) group and the medication (drugs administered alone) group at the ratio of 1:1., in order to evaluate if the interventional treatment is better than the medication alone in these patients, to assess the efficacy and safety of the made-in-China occluders in the interventional treatment and prevention of PFO-induced migraine, and to identify the incidence of PFO in the patients with migraine in China and develop the Chinese people-specific screening protocols of PFO-induced migraine.

Study Overview

• Status: Unknown
• Conditions: Patent Foramen Ovale
• Intervention / Treatment: Procedure: the transcatheter closure of PFO

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhang Yu Shun, PHD; Phone Number: 0086-029-85324625; Email: zys2889@sina.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • First Affiliated Hospital of Xian JiaotongUniversity
      • Contact: Zhang Yu Shun, PHD; Phone Number: 0086-029-85324625; Email: zys2889@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• migraine headaches with or without aura,migraine onset before age 50
• >3 migraine attacks or 5 migraine days per month
• failed ≥2 commonly accepted migraine medications:β-receptor blockers, calcium-ion antagonists, antidepressants and non-steroid anti-inflammatory drugs (NSAID).
• PFO documented by TTE or TEE
• PFO meet one of the following conditions:RLS in rest documented by cTTE or cTCD,combine with ASA,the primary patition mobility≥6.5mm,the diameter of PFO≥4mm, combine with Eustachian Valve or Chiari net.
• age 18-60
• else:independent in daily activities,to comply with complete follow-up experiment design

Exclusion Criteria:

• contraindication to antiplatelet or anticoagulant
• inferior vena cava or pelvic vein thrombogenesis leading to complete obstruction,systemic or local infection,septicemia,heart lumen thrombosis
• pregnancy
• combine with pulmonary hypertension or PFO made for a particular channel
• severe allergy to nickel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the closure group; In the closure group, the transcatheter closure of PFO was performed using the made-in-China occluders approved by SFDA, in combination of clopidogrel(50mg/d, 3mon) and aspirin (0.1g/d, 6mon), i.e. oral administration of aspirin (0.1g/d) and clopidogrel (50mg/d) at 48h before the closure; the low molecular weight heparin (LMWH) was routinely given at 48h after the closure; and some pain-relief drugs could be temporarily administered in the patients with acute onset of migraine.	Procedure: the transcatheter closure of PFO; the transcatheter closure of PFO was performed using the made-in-China occluders approved by SFDA,clopidogrel(50mg/d, 3mon) , aspirin (0.1g/d, 6mon), i.e. oral administration of aspirin (0.1g/d) and clopidogrel (50mg/d) at 48h before the closure; the low molecular weight heparin (LMWH) was routinely given at 48h after the closure; and some pain-relief drugs could be temporarily administered in the patients with acute onset of migraine.
No Intervention: the medication group; In the medication group, in combination of clopidogrel (50mg/d, 3mon) and aspirin (0.1g/d, 6mon), current medication resumed, including conventional prescription for migraine as β-receptor blockers, calcium-ion antagonists, antiepileptics, antidepressants and non-steroid anti-inflammatory drugs (NSAID).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
migraine days after randomization	up to 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Southwest Hospital, China; Air Force Military Medical University, China; Second Affiliated Hospital of Xi'an Jiaotong University
• Investigators: Study Chair: Zhang Yu Shun, PHD, First Affiliated Hospital of Xian JiaotongUniversity

Publications and helpful links

General Publications

• Zhao E, Du Y, Xie H, Zhang Y. Modified Method of Contrast Transthoracic Echocardiography for the Diagnosis of Patent Foramen Ovale. Biomed Res Int. 2019 May 9;2019:9828539. doi: 10.1155/2019/9828539. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 4, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: treatment; migraine; patent foramen ovale
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Congenital Abnormalities; Headache Disorders, Primary; Headache Disorders; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Migraine Disorders; Headache; Foramen Ovale, Patent
• Other Study ID Numbers: XJTU1AF-CRF-2015-008