Probiotics as Adjunctive Migraine Prophylaxis

October 31, 2022 updated by: Wan Aliaa Wan Sulaiman, Universiti Putra Malaysia

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
64

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Malaysia
    • Selangor Darul Ehsan
      • Serdang, Selangor Darul Ehsan, Malaysia, 43400
        • Recruiting
        • University Putra Malaysia
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Azliza Ibrahim, MMED
        • Sub-Investigator:
          • Anna Misyail Rashid, MMED

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline in mean monthly migraine days (MMD).
Time Frame: Baseline, week 4, 8 and 12 post treatment
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in mean monthly migraine attacks
Time Frame: Baseline, week 4, 8 and 12 post treatment
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)
Time Frame: 12 weeks post treatment
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
Time Frame: Baseline, week 4, 8 and 12 post treatment
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
Time Frame: Week 4, 8 and 12 treatment
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)
Time Frame: Week 0 and 12 post treatment
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)
Time Frame: Week 0 and 12 post treatment
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
Time Frame: Week 0 and 12 post treatment
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)
Time Frame: Week 0 and 12 post treatment
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)
Time Frame: Week 0 and 12 post treatment
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)
Time Frame: Week 0 and 12 post treatment
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
Time Frame: Week 0 and 12 post treatment
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universiti Putra Malaysia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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