Complex Regional Pain Syndrome (CRPS) and the Gut-bacteria

Comparison of Gut Microbial Composition and Function in CRPS Patients vs. Healthy Individuals

The purpose of this study is to investigate, for the first time, whether gut bacteria composition and function of patients with CRPS differ from those of healthy adults. Samples of stool, urine and blood will be collected from patients with CRPS and from healthy adults. The type and function of bacteria of CRPS patients will be analyzed and compared to those of healthy adults to test if potential differences could explain the mechanism/s involved with the development of CRPS.

Study Overview

• Status: Active, not recruiting
• Conditions: CRPS
• Intervention / Treatment: Diagnostic test: Stool and blood samples; Other: Physical examination; Other: Questionnaires

• Study Type: Observational
• Enrollment (Anticipated): 250

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: All

• Sampling Method: Non-Probability Sample

Study Population

Adult women and men with CRPS and healthy volunteers.

Description

Inclusion criteria:

1. Women and men over the age of 18, diagnosed with CRPS of the upper or lower limb according to the Clinical Budapest Criteria, with a duration of 6 months and over (for the 1st study group).
2. Healthy women and men over the age of 18, who share a household with a CRPS patients participating in the study (for the 1st control group).
3. Healthy women and men over the age of 18 (for the 2nd control group).
4. Be able to read and write in either French, English or Hebrew.

Exclusion criteria:

1. Any major illness (eg. malignancy, active inflammatory disease, metabolic disease, etc.)
2. Pregnancy
3. Chronic pain conditions (other than CRPS in the patients group)
4. Acute illness of any type in the preceding 1 month
5. Use of systemic antibiotics in the preceding 1 month
6. Change in any other regularly taken medications in the past 1 month
7. Substantial dietary / gastrointestinal alterations in the past 1 month.

The inclusion/exclusion criteria were set to reduce the risk of confounding factors that could affect gut microbiota composition.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CRPS (Complex Regional Pain Syndrome); Participants with CRPS (Complex Regional Pain Syndrome))	Diagnostic test: Stool and blood samples; fecal microbiome and metabolomics, as well as metabolites in plasma; Other: Physical examination; physical examination performed by a physician to confirm CRPS diagnosis and assess patient's eligibility to participate in the study. The exam will include skin temperature measured using a laser/infrared skin thermometry.; Other: Questionnaires; Questionnaires measuring pain level, sleep, mood and diet parameters.
Healthy; Healthy individuals	Diagnostic test: Stool and blood samples; fecal microbiome and metabolomics, as well as metabolites in plasma; Other: Questionnaires; Questionnaires measuring pain level, sleep, mood and diet parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome composition	Assessment of genomic composition of the gut bacteria by differential abundance analysis will be performed using 16S rRNA (Genome-Quebec)	1 day
Presence of stool microbiota-related metabolites affecting host physiology	Concentration of bile acids and short-chain-fatty-acids through Metabolomics analysis (Metabolon, USA).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-form health-questionnaire (SF12) score	A 12-item measure of health-related quality of life, validated in a variety of population groups	1 day
Brief Pain Inventory (BPI) score	A 12-item questionnaire evaluating function level and disability among pain patients	1 day
Patient Health Questionnaire (PHQ-9) score	A 9 item inventory rated on a 4 point Likert-type scale used for screening for depression and anxiety	1 day
Pittsburg Sleep Quality Index (PSQI) scores	A standardized self-administered questionnaire for the assessment of subjective sleep quality	1 day

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Rambam Health Care Campus; 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

• 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.
• Birklein F, Ajit SK, Goebel A, Perez RSGM, Sommer C. Complex regional pain syndrome - phenotypic characteristics and potential biomarkers. Nat Rev Neurol. 2018 May;14(5):272-284. doi: 10.1038/nrneurol.2018.20. Epub 2018 Mar 16.
• Birklein F, O'Neill D, Schlereth T. Complex regional pain syndrome: An optimistic perspective. Neurology. 2015 Jan 6;84(1):89-96. doi: 10.1212/WNL.0000000000001095. Epub 2014 Dec 3. Review.
• Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007 May-Jun;8(4):326-31. doi: 10.1111/j.1526-4637.2006.00169.x.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Actual): October 14, 2022
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 25, 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

• Other Study ID Numbers: CRPS-MB 2021-6735

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