The Effect of Probiotics on the Frequency and Intensity of Migraine Attacks and Intestinal Permeability (Promi2)

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

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.

Study Overview

• Status: Unknown
• Conditions: Migraine
• Intervention / Treatment: Dietary supplement: EcologicBarrier; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Wageningen University
• Investigators: Principal Investigator: Nicole De Roos, PhD, Wageningen UR

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 14, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: NL46401.081.13