Fecal Microbiota Transplantation for Patients With Chronic Widespread Pain

Study Overview
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Brief Summary
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This study aims to explore the effect of Fecal Microbiota Transplantation (FMT) on the clinical symptomatology in Chronic Widespread Pain (CWP), to assess the acceptability, tolerability, and safety of FMT in patients with CWP, as well as explore the effect of FMT on the gut microbiome diversity in CWP. The investigators hypothesize that fecal microbiota transplantation will reduce pain intensity in patients with CWP, is acceptable, safe, and tolerable in patients with CWP, and will achieve change of gut microbiome diversity after FMT treatment.

Detailed Description
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In this proposed proof-of-concept pilot study, the investigators capitalize an establish chronic pain cohort to explore the effect of FMT in improving the pain symptomology in patients with CWP. This will be a 12-week single-arm prospective interventional study, all study subjects will receive 3 FMT infusions (N =20).

Official Title
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Fecal Microbiota Transplantation for Patients With Chronic Widespread Pain: A Pilot Prospective Single-arm Interventional Study

Conditions
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Chronic Widespread Pain

Intervention / Treatment
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* Procedure: Fecal Microbiota Transplantation
* Procedure: Sigmoidoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Participants aged ≥ 18 with diagnosis CWP; A modified version of the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) will be used to screen for the presence of CWP. Exclusion Criteria: Patients with fibromyalgia, a subgroup with complex neurobiological, behavioural and psychological factors on its pathogenesis, will be excluded.[8] This will be based on The American College of Rheumatology 2010 when subjects with CWP but with a widespread pain index (WPI) of ≥ 7 and a symptom severity scale (SSS) score of ≥ 5 or a WPI between 3 and 6 and an SSS score of ≥ 9. Patients have a history of inflammatory bowel disease or gastrointestinal malignancy Patients have previous abdominal surgery (other than cholecystectomy or appendectomy) Patients have depression defined by having a Patient Health Questionnaire-9 (PHQ-9) score > 15 Patients have anxiety defined by having a Generalized Anxiety Disorder 7 (GAD7) score > 10 Patients have active infection at the time of inclusion Patients have used antibiotic therapy or anti-inflammatory drugs within the past 7 days Patients have any other organic causes that can explain the symptoms of CWP Current pregnancy Confirmed current active malignancy or cancers Pregnancy test negative for all female patients of child-bearing potential (except postmenopausal patients and sterilized patients).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic Widespread Pain patients<br>3 FMT infusions, 2 weeks apart Procedures for Infusion: 100-200 ml of FMT solution or sterile saline will be infused over 2-3 minutes into the distal duodenum or jejunum via oesophago-gastro-duodenoscopy (OGD). After infusion, subjects will be monitored for 1 hour before discharged. | Procedure: Fecal Microbiota Transplantation<br>* FMT performed at week 0, week-2 and week-4: FMT solution will be prepared using stool from a single donor or mixing of stool from multiple donors. Feces will be diluted with sterile saline (0.9%). This solution will be blended and strained with filter. The resulting supernatant will then be used directly as fresh FMT solution or stored as frozen FMT solution for future FMT. Procedures for Infusion: 100-200 ml of FMT solution or sterile saline will be infused over 2-3 minutes into the distal duodenum or jejunum via oesophago-gastro-duodenoscopy (OGD). After infusion, subjects will be monitored for 1 hour before discharged. 2 study biopsies in total (from duodenum) will be obtained during FMT infusion via OGD.<br>Procedure: Sigmoidoscopy<br>* Optional sigmoidoscopy will be done at week 0 and week 4, during which 2 study biopsies in total (obtained via sigmoidoscopy) will be obtained from the rectum.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in self-reported pain severity | Pain severity will be measured by Brief Pain Inventory (BPI), which consists of 4-item severity and 7-item interference subscale scores (Score range 0-10) | Study week 0 , 6 , 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of supplementation of FMT | Adverse events will be monitored throughout the study | through study completion, an average of 1 year | 
| Changes in objectively measured pain pressure threshold | Fischer pressure algometer will be used for measuring pain pressure threshold (PPT). | Study week 0 , 6 , 12 | 
| Changes in comorbid psychopathology (anxiety symptoms) | The Generalized Anxiety Disorder (GAD-7, score range 0-21) will be used to measure anxiety status | Study week 0 , 6 , 12 | 
| Changes in comorbid psychopathology (depressive symptoms) | The Patient Health Questionnaire (PHQ-9, score range 0-27) will be used to measure anxiety status | Study week 0 , 6 , 12 | 
| Changes in health-related quality of life | The overall the health-related quality of life (HRQoL) will be measured by the EuroQoul-5 dimensions questionnaire (EQ-5D-5L) | Study week 0 , 6 , 12 | 
| Changes in Alpha diversity index of gut microbiota | Alpha diversity of the gut microbiome using the Shannon's and inverse Simpson indices will be computed from the operational taxonomic units (OTUs) | Study week 0 , 6 , 12 | 
| Sociodemographic data | Demographics and medical history such as sex, age, smoking and alcohol status, disease onset, co-morbid illness, drug history, clinical test results will be obtained by reviewing of patient medical notes and interview with patients by doctors and research staff | At baseline, Study week 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut Microbiota, Fecal Microbiota Transplantation