NCT03521193: LEARNER

pLatelEts And MigRaine iN patEnt foRamen Ovale

Completed NA Results posted Last updated 19 April 2024

What this trial tests

NA trial testing patent foramen ovale closure in Platelet Aggregation, Spontaneous in 90 participants. Completed in 31 October 2020.

Timeline

15 February 2018

Primary endpoint
31 October 2020

31 October 2020

Quick facts

Lead sponsor	Centro Cardiologico Monzino
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	90
Start date	15 February 2018
Primary completion	31 October 2020
Estimated completion	31 October 2020
Sites	1 location across Italy

Drugs / interventions tested

• patent foramen ovale closure

Conditions studied

• Platelet Aggregation, Spontaneous — all drugs for Platelet Aggregation, Spontaneous →
• Migraine With Aura — all drugs for Migraine With Aura →
• Patent Foramen Ovale — all drugs for Patent Foramen Ovale →

Sponsor

Centro Cardiologico Monzino — full company profile →

Who can join

Adults 18 to 70, any sex, with Platelet Aggregation, Spontaneous or Migraine With Aura. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Migraine Characteristics Primary · The outcome data were evaluated at 6-months and 12-months after PFO closure and compared to baseline

The evaluation in absolute numbers of patients fully responders, non-responders or with a moderate benefit on migraine symptoms after PFO Closure was performed

Migraine : Complete Migraine Resolution

Group	Value	95% CI
Migraine Assessment After PFO Closure	43

Migraine : Non-responders

Group	Value	95% CI
Migraine Assessment After PFO Closure	2

Migraine Symptoms improvement

Group	Value	95% CI
Migraine Assessment After PFO Closure	17

Migraine Assessment by Anzola's Score Primary · Baseline, 6 months and 12-months after PFO closure

The change in migraine severity, incidence and duration with or without aura as measured by the Anzola's score (The score is the expression of the sum of each corresponding value referring to migraine duration, frequency and the presence or absence of aura). The minimum value was 2 and the maximum 9; the higher the value, worse is the migraine classification. Anzola's score: Duration 0=No pain 1=\<6 hours 2=6-12 hours 3=\>12 hours Frequency 0=No pain 1=1-4/month 2=5-9/month 3=\>10/month Aura 0=No aura 1=Aura in ≥1 attack

Anzola's score @Baseline

Group	Value	95% CI
PFO Patients Enrolled	7.2	± 1.68

Anzola's score@6-mos post PFO Closure

Group	Value	95% CI
PFO Patients Enrolled	1.09	± 1.47

Anzola's score @12-mos post PFO closure

Group	Value	95% CI
PFO Patients Enrolled	1.1	± 1.57

Platelet Activation (I) Secondary · baseline and 6 months after PFO closure

Platelet Thrombin generation potential in migraineurs and healthy subjects

Lag Time

Group	Value	95% CI
PFO Patients	26.9	± 8.9
Healthy Subjects	30.6	± 7.2
PFO Patients at T1 (6 Mos)	32.2	± 12.4

Time to peak

Group	Value	95% CI
PFO Patients	32.1	± 9.5
Healthy Subjects	37.6	± 10.2
PFO Patients at T1 (6 Mos)	37.8	± 13

Platelet Activation (II) Secondary · Baseline and 6 months after PFO closure

Platelet Thrombin generation Potential in Migraneurs and Healthy subjects

Group	Value	95% CI
PFO Patients	29.1	± 29
Healthy Subjects	12.3	± 10.9
PFO Patients at T1 (6 Mos)	17.9	± 19.9

Platelet Activation (III) Secondary · baseline and six months after PFO closure

Platelets' endogenous thrombin generation potential in Migraneurs and Healthy subjects

Group	Value	95% CI
PFO Patients at Baseline T0	1038	± 352
Healthy Subjects	781	± 319
PFO Patients at T1 (6 Mos)	797	± 373

Platelet Activation (IV) Secondary · Baseline and six-months after PFO closure

Platelets' functional activity measured as the amount of thrombin generation

Group	Value	95% CI
PFO Patients at Baseline T0	115.2	± 81.2
Healthy Subjects	63.4	± 41.8
PFO Patients at T1 (6 Mos)	77.2	± 59.2

Platelet Aggregation (I) Secondary · baseline and 6 months after PFO Closure

Platelet aggregation was measured on PAP-8 aggregometer (BioData). Briefly, PRP aliquots (250µL) were pipetted into a siliconized glass cuvette, stirred at 1200 rpm at 37°C and stimulated with arachidonic acid (1mM), collagen (2µg/ml), ADP (5µM), TRAP-6 (5µM). Light transmission was recorded for 5 min after stimuli addition and platelet aggregation was reported as maximal percentage of light transmission. Aspirin-treated patients were considered drug responders when platelet aggregation was less than 20% after arachidonic acid (1mM) stimulation.

ADP (5µM)

Group	Value	95% CI
PFO Patients at T0	153	92.5 – 210
PFO Patients at T1	157	92 – 216
Healthy Subjects	187	116 – 253

TRAP-6 (5µM)

Group	Value	95% CI
PFO Patients at T0	8.5	5 – 14
PFO Patients at T1	8	4 – 13
Healthy Subjects	11	9 – 27

Collagen (2µg/ml)

Group	Value	95% CI
PFO Patients at T0	62	23.7 – 121.2
PFO Patients at T1	76.5	30.2 – 139.5
Healthy Subjects	104	73 – 184

Clinical Outcomes Secondary · In hospital, six and 12 months follow-up

Absence of TIA and stroke recurrences after PFO closure and during the follow-up

In -hospital vascular complications

Group	Value	95% CI
PFO Patients Enrolled	1

device malpositioning/embolization

Group	Value	95% CI
PFO Patients Enrolled	0

Transient atrial fibrillation

Group	Value	95% CI
PFO Patients Enrolled	5

TIA/stroke post PFO Closure

Group	Value	95% CI
PFO Patients Enrolled	0

Recurrent TIAs /stroke @6 months FU

Group	Value	95% CI
PFO Patients Enrolled	0

Recurrent TIAs /stroke @12 months FU

Group	Value	95% CI
PFO Patients Enrolled	0

Sponsor's own description

Migraine is a common, chronic neurovascular disorder characterized by attacks of severe headache, autonomic nervous system dysfunction and, in some patients, aura, and disabling neurological symptoms. Worldwide, migraine prevalence is as high as 18% in the general population. Increased frequency of patent foramen ovale (PFO) in migraineurs was first reported in 1998 in a case-control study. Since then, others have described a 60% prevalence of PFO in patients suffering from migraine with aura. The presence of a right-to-left shunt (RLS) is thought to be a potent trigger of migraine attacks, although the mechanism is unknown. Moreover, PFO closure has correlated with improved migraine symptoms in several retrospective uncontrolled studies. The aim of this single-center, prospective study is to assess the impact of PFO closure on migraine attacks over time together with evaluation of potential predictive risk factors.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study.
   Trabattoni D, Brambilla M, Canzano P, Becchetti A, et al · · 2022 · cited 38× · PMID 35818509 · DOI 10.1016/j.jacbts.2022.02.002