The Effect of Probiotics on the Frequency and Intensity of Migraine Attacks and Intestinal Permeability

Study Overview
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Brief Summary
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RATIONALE: The prevalence of migraine is higher in patients with various intestinal diseases. An explanation could be that migraine is caused by a 'leaky gut': an increased intestinal permeability that allows food particles to pass the gastrointestinal wall. Probiotics may be able to improve intestinal barrier function. OBJECTIVE: To test whether probiotics, as adjuvant therapy, can reduce incidence and severity of migraine attacks by reducing intestinal permeability. STUDY DESIGN: 12-week placebo-controlled randomized double-blind intervention with selected probiotics. STUDY POPULATION: Adults who experience at least 4 migraine attacks per month. INTERVENTION: Subjects will receive either one daily dose of 2 g of Ecologic® Barrier or 2 grams of the placebo, containing only the carrier material (both provided by Winclove Probiotics). MAIN STUDY PARAMETERS/ENDPOINTS: Incidence and severity of migraine attacks, measured by diaries and validated headache questionnaires will be measured at baseline and after 4, 8, and 12 weeks of probiotic/placebo administration. Secondary, intestinal permeability will be measured by the lactulose/mannitol absorption test in urine (screening, baseline and 12 weeks) and by fecal zonulin (baseline, 4, 8, and 12 weeks). Inflammation will be assessed from blood C-reactive protein and cytokine concentrations (baseline, 4, 8, and 12 weeks). Fecal samples will also be used for microbial analysis.

Official Title
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The Effects of Probiotics on the Frequency and Intensity of Migraine Attacks and Intestinal Permeability. A Placebo-controlled Trial

Conditions
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Migraine

Intervention / Treatment
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* Dietary Supplement: EcologicBarrier
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects confirm to have migraine characterized by : Recurrent attacks of moderate to severe headaches, often one-sided and pounding, often with nausea and/or vomiting, aggravated by physical activity Sensitivity for light or sounds is possible but not exclusive. Attacks last for 4 to 72 hours. Self-reported frequency of migraine attacks (or days) at least 4 per month Fairly predictable/stable pattern of migraine attacks (frequency, duration, intensity) Age ≥ 18 years Good overall health (self-reported in medical questionnaire) Exclusion Criteria: Migraine patients who suffer from chronic daily migraine/headaches Migraine patients who suffer from medication-dependent headaches Subjects who suffer from cluster headache or tension-type headaches Subjects who used antibiotics up to two months before the start of the study Subjects who are unwilling to stop taking probiotics other than study products Patients with a chronic use of non steroid anti inflammatory drugs (because of increased gut permeability) Patients with inflammatory bowel diseases (because of increased gut permeability) Pregnancy or lactation (because of their possible effect on migraine incidence)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br>EcologicBarrier, 5x10E9 cfu/day | Dietary Supplement: EcologicBarrier<br>* multispecies probiotic product, 2x10-9 cfu/gram<br>|
| Placebo Comparator: Placebo<br>carrier material of Ecologic Barrier, not containing bacterial strains | Other: Placebo<br>* similar appearance as the probiotic product, but without bacteria<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of migraine attacks |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal permeability | Lactulose/mannitol in urine, zonulin in serum | 12 weeks | 
| Inflammation markers. | pro-inflammatory cytokines in serum | 12 weeks |