Fecal Microbiota Transplantation for Patients With Chronic Widespread Pain

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

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.

Study Overview

• Status: Suspended
• Conditions: Chronic Widespread Pain
• Intervention / Treatment: Procedure: Fecal Microbiota Transplantation; Procedure: Sigmoidoscopy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Chinese University of Hong Kong

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chronic Widespread Pain patients; 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; 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.; Procedure: Sigmoidoscopy; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood sample (Full blood count)	Not more than 20ml of blood will be collected	Study week 0, 2, 4, 6, 12
Number of participants with With Laboratory Values (Biochemistry profile)	Not more than 20ml of blood will be collected	Study week 0, 2, 4, 6, 12
Blood sample (C-reactive protein)	Not more than 20ml of blood will be collected	Study week 0, 2, 4, 6, 12
Stool sample	Stool sample collected through stool sample collection kit with Norgen preservation solutions	Study week 0, 6, 12

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Regina Wing Shan Sit, MD, The Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Gut Microbiota
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: 2022.295

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