Probiotics as Adjunctive Migraine Prophylaxis

The Effectiveness and Tolerability of Multi-Strain Probiotics as Adjunctive Preventive Treatment of Episodic Migraine: A Single Centre, Randomised, Double- Blind, Sham-Controlled Phase 2 Trial (PROBIOTICS -EM).

This study will assess the safety and efficacy of multi-strain probiotics as an adjunctive treatment for episodic migraine

Study Overview

• Status: Recruiting
• Conditions: Migraine; Episodic Migraine
• Intervention / Treatment: Other: Placebo; Dietary supplement: (Microbial cell preparation) probiotics

Detailed Description

This is a phase 2 and single center, randomized, placebo-controlled double-blind clinical Trial. Episodic migraine patients according to International Headache Society criteria will be allocated randomly into two treatment arms. One group will receive active probiotics and another group will receive placebo for treatment phase. Both groups of patients will consume the treatment twice daily for 12 weeks and assessment will be made at baseline, baseline, week 4, 8 and 12

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Azliza Ibrahim, MMED; Phone Number: 60134888405 +60172640768; Email: azliza.i@upm.edu.my
• Study Contact Backup: Name: Hrishikesa Kumar, MBBS; Phone Number: +0174888979; Email: hrishikesa87@ymail.com

Study Locations

• Malaysia
  • Selangor Darul Ehsan
    • Serdang, Selangor Darul Ehsan, Malaysia, 43400
      • Recruiting
      • University Putra Malaysia
      • Contact: Wan Aliaa Wan Sulaiman, FRCP; Phone Number: 603 8609 2980; Email: wanaliaa@upm.edu.my
      • Contact: Azliza Ibrahim, MMed; Phone Number: 0172640768; Email: azliza.i@upm.edu.my
      • Sub-Investigator: Azliza Ibrahim, MMED
      • Sub-Investigator: Anna Misyail Rashid, MMED

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects fulfilling criteria for episodic migraine as per the Third Edition of The International Headache Society (ICHD-3) (Table 1)
2. Patients diagnosed with episodic migraine (4 or more episodes per month) for a minimum of 3 months.
3. On a steady treatment regimen: preventive and acute migraine medications and therapies unchanged over the last 3 months
4. Adult patients Age > 18 years old
5. A signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study including any known and potential risks and available alternative treatments.

Exclusion Criteria:

1. Lactose intolerance
2. Previous history of small and large bowel surgery
3. Use of probiotics or antibiotics in 2 weeks before baseline visit.
4. Patients with medical conditions such as severe hypertension, infections,
5. Malignancy, cardiovascular and cerebrovascular diseases, epilepsy, degenerative central nervous system diseases, renal failure, hepatic failure, bleeding diathesis and serious mental illnesses
6. Headache with red flags symptoms that may suggest organic secondary headaches.
7. Onset of headache more than 50 years
8. Prior GI infection in the previous 3-months
9. Morbid obesity (BMI >40)
10. Pregnant or lactating women

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
Active Comparator: Double-blind, placebo-controlled interventional study; Active treatment group will receive a 3-gram sachet of probiotics containing multi-strain of lactobacillus and Bifidobacterium 30 Colony Forming Unit x 109 to be taken twice daily for 12 weeks.	Dietary supplement: (Microbial cell preparation) probiotics; Lactobacillus acidophilus (107mg), Lactobacillus casei subsp (107mg), Lactobacillus lactis (107mg), Bifidobacterium bifidum (107mg), Bifidobacterium infantis (107mg) and Bifidobacterium longum (107mg); Other Names: Hexbio; Granulated Multi-strain Probiotics
Placebo Comparator: Placebo; Patients will be given placebo sachet (exactly the same packaging as active comparator) to be taken 1 sachet twice daily for 12 weeks.	Other: Placebo; Placebo sachet with no microbial cell preparation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean monthly migraine days (MMD).	The MMD will be calculated using the MMD recorded by patients in a headache diary from each of the months of the double-blind treatment phase.	Baseline, week 4, 8 and 12 post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean monthly migraine attacks	The mean monthly migraine attacks will be calculated using the monthly migraine attack recorded by patients in headache diaries from each of the months of the double-blind treatment phase	Baseline, week 4, 8 and 12 post treatment
Reduction mean monthly migraine days(MMD)	Proportion of subjects with at least a 50% reduction from baseline in MMD	12 weeks post treatment
Change from baseline in mean monthly pain intensity of migraine attacks	The mean monthly pain intensity will be based on the record of the maximal pain intensity by means of a verbal scale (i.e., 0 =no headache; 1 = mild headache; 2 = moderate headache; 3 = severe headache) prior to taking symptomatic medication	Baseline, week 4, 8 and 12 post treatment
Adverse events in response to probiotics	Frequency and adverse events in response to (probiotics)	Week 4, 8 and 12 treatment
Change from baseline in mean Migraine Induced Disability Assessment Score (MIDAS)	Change from baseline in mean Migraine Induced Disability Assessment Score (MIDAS) in migraine patients in response to probiotics	Week 0 and 12 post treatment
Change from baseline in mean Depression, Anxiety and Stress Scale (DASS21)	Change from baseline in mean Depression, Anxiety and Stress Scale (DASS21) score in migraine patients in response to probiotics	Week 0 and 12 post treatment
Change from baseline in mean Migraine-Specific Quality-of-Life Questionnaire (MSQ V2) score	Change from baseline in mean Migraine-Specific Quality-of-Life Questionnaire (MSQ V2) score in migraine patients in response to probiotics	Week 0 and 12 post treatment
Serum Highly sensitive C-Reactive Protein (hs-CRP)	Highly sensitive C-Reactive Protein (hs-CRP) level changes in migraine patients in response to probiotics	Week 0 and 12 post treatment
Serum Interleukin 6 (IL- 6)	Interleukin 6 (IL- 6) level changes in migraine patients in response to probiotics	Week 0 and 12 post treatment
Serum Tumour Necrosis Factor Alpha (TNF-alpha)	Tumour Necrosis Factor Alpha (TNF-alpha) level changes in migraine patients in response to probiotics	Week 0 and 12 post treatment
Satisfaction measures of efficacy, tolerability, safety, and expectations of probiotics among the participants	A 5-point, Likert scale will be used to evaluate satisfaction with probiotics in migraine prevention	Week 0 and 12 post treatment

Collaborators and Investigators

• Sponsor: Universiti Putra Malaysia
• Investigators: Study Chair: Hamidon Basri, AM, University Putra Malaysia; Principal Investigator: Wan Aliaa Wan Sulaiman, FRCP, University Putra Malaysia; Study Director: Azliza Ibrahim, MMed, Universiti Putra Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Episodic migraine, probiotics, effectiveness, preventive treatment, randomized controlled trial.
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: JKEUPM-2021-276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No