The Effects of Dietary Changes on Gut-bacteria and Fibromyalgia Symptoms

Microbiome Correlates of Dietary Interventions in Patients With Fibromyalgia and Their Association With Symptom Modification

The purpose of this study is to evaluate the efficacy of two diets - gluten-free and low-FODMAP diet- in relieving symptoms of fibromyalgia, and study whether these changes could be associated with changes in the gut microbiome (gut bacteria).

Study Overview

• Status: Active, not recruiting
• Conditions: Fibromyalgia; Diet, Gluten-Free
• Intervention / Treatment: Behavioral: Low-FODMAP diet; Behavioral: Gluten-free Diet; Behavioral: Control group

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Alan Edwards Pain Management Unit - Montreal General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Women over the age of 18, diagnosed with FM.
2. Chronic widespread pain index >= 9 and pain intensity >= 6.
3. Able to read and write in either French or English.

Exclusion Criteria:

1. Any major illness (e.g. malignancy, active inflammatory disease, metabolic disease, etc.)
2. Inflammatory bowel disease.
3. Severe depression (HADS score for depression > 10).
4. Current use of LFD or GFD.
5. Pregnancy
6. Vegan diet

The inclusion/exclusion criteria were set to reduce the risk of confounding factors that could affect gut microbiota composition. To date, information on microbiome alterations in individuals with fibromyalgia is only available for female patients, and thus recruitment will be limited to women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-FODMAP Diet; Participants will be instructed to maintain their usual diet, while eliminating FODMAPs (A subgroup of carbohydrates are considered fermentable, given the lack of suitable hydrolase enzymes in the colon, required for their digestion and absorption, thus making them available for fermentation).	Behavioral: Low-FODMAP diet; Participants will be instructed to maintain their usual diet, while eliminating all dietary gluten.
Experimental: Gluten-Free Diet; Participants will be instructed to maintain their usual diet, while eliminating all dietary gluten.	Behavioral: Gluten-free Diet; Participants will be instructed to maintain their usual diet, while eliminating all dietary gluten.
Other: Control; Patients of this group will be asked to adhere to their regular, daily diet.	Behavioral: Control group; Patients of this group will have dietary consultation but will not change their regular diet for the period of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiome composition in response to dietary intervention	Genome structure, structural variants - Differential abundance analysis will be performed using 16S rRNA.	Four weeks after the initiation of the new diet compared to baseline.
Changes in stool microbiota-related metabolites affecting host physiology, in response to dietary intervention.	Metabolomics analysis will be performed (Metabolon, USA) - targeted metabolomic for bile acids and SCFA analysis.	Four weeks after the initiation of the new diet compared to baseline.
Changes in blood microbiota-related metabolites, affecting host physiology, in response to dietary intervention	Metabolomics analysis will be performed (Metabolon, USA) - targeted metabolomic for bile acids and SCFA analysis.	Four weeks after the initiation of the new diet compared to baseline.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Fibromyalgia Survey Diagnostic Criteria and Severity Scale (FSDC) scores.	assessing symptom severity, pain distribution, fatigue, sleep quality and cognitive and somatic complaints in fibromyalgia patients. A questionnaire assessing symptom severity, pain distribution, fatigue, sleep quality and cognitive and somatic complaints in fibromyalgia patients.	Four weeks after the initiation of the new diet compared to baseline.
The Fibromyalgia Impact Questionnaire (FIQ) score	A 10 items questionnaire evaluating physical functioning, work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety and depression.	Four weeks after the initiation of the new diet compared to baseline.
Hospital Anxiety and Depression Scale (HADS) score	A 14-items questionnaire assessing the level of depression and anxiety.	Four weeks after the initiation of the new diet compared to baseline.
The Pittsburg Sleep Quality Index scores	An 11 item sleep quality evaluation questionnaire.	Four weeks after the initiation of the new diet compared to baseline.
ROME IV criteria for irritable bowel syndrome	Four yes-or-no items	Four weeks after the initiation of the new diet compared to baseline.

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Louise and Alan Edwards Foundation
• Investigators: Principal Investigator: Yoram Shir, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Bauer KC, Huus KE, Finlay BB. Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis. Cell Microbiol. 2016 May;18(5):632-44. doi: 10.1111/cmi.12585. Epub 2016 Mar 31. Review.
• Minerbi A, Gonzalez E, Brereton NJB, Anjarkouchian A, Dewar K, Fitzcharles MA, Chevalier S, Shir Y. Altered microbiome composition in individuals with fibromyalgia. Pain. 2019 Nov;160(11):2589-2602. doi: 10.1097/j.pain.0000000000001640.
• Thaiss CA, Itav S, Rothschild D, Meijer MT, Levy M, Moresi C, Dohnalova L, Braverman S, Rozin S, Malitsky S, Dori-Bachash M, Kuperman Y, Biton I, Gertler A, Harmelin A, Shapiro H, Halpern Z, Aharoni A, Segal E, Elinav E. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016 Dec 22;540(7634):544-551. doi: 10.1038/nature20796. Epub 2016 Nov 24.
• Tong M, Li X, Wegener Parfrey L, Roth B, Ippoliti A, Wei B, Borneman J, McGovern DP, Frank DN, Li E, Horvath S, Knight R, Braun J. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One. 2013 Nov 19;8(11):e80702. doi: 10.1371/journal.pone.0080702. eCollection 2013.
• Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015 Aug;21(8):895-905. doi: 10.1038/nm.3914. Epub 2015 Jul 27.
• Lowry E, Marley J, McVeigh JG, McSorley E, Allsopp P, Kerr D. Dietary Interventions in the Management of Fibromyalgia: A Systematic Review and Best-Evidence Synthesis. Nutrients. 2020 Aug 31;12(9). pii: E2664. doi: 10.3390/nu12092664.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: Diet-FM/2020-6134

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
• product manufactured in and exported from the U.S.: No