## Protocol Section
### Identification Module
**NCT ID:** NCT06424041

**Acronym:** FM-FMT-RCT

**Brief Title:** Fecal Microbiome Transplantation From Healthy Donors to Individuals With Fibromyalgia

**Official Title:** Fecal Microbiome Transplantation From Healthy Donors to Individuals With Fibromyalgia: A Prospective Randomized, Controlled Double-Blind Study

#### Organization Study ID Info
**ID:** 0521-23
#### Organization
**Class:** OTHER
**Full Name:** Rambam Health Care Campus
#### Secondary ID Infos
**Domain:** Weston Family Foundation
**ID:** Weston Family Foundation
**Type:** OTHER_GRANT
**Domain:** Israel Science Foundation
**ID:** Israel Science Foundation
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2027-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-11

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Rambam Health Care Campus

#### Responsible Party

**Investigator Affiliation:** Rambam Health Care Campus

**Investigator Full Name:** Amir Minerbi MD

**Investigator Title:** Deputy Director

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study aims to investigate if a fecal microbiome transplantation (FMT) from healthy donors can reduce symptoms of fibromyalgia, a condition causing chronic pain that is difficult to treat and diagnose. Changes in the gut bacteria of women with fibromyalgia were previously reported, which might be linked to their symptoms. In mice studies, transferring gut bacteria from individuals with fibromyalgia was shown to increase sensitivity to pain, while treatment with antibiotics and transferring bacteria from healthy individuals reversed this effect. In a small open label trial in women, improvements in pain, fatigue, and sleep problems were observed after FMT. The investigators aim to perform a larger trial following a similar path. The study aims to conduct a double-blinded, randomized, placebo-controlled trial involving 80 women diagnosed with severe fibromyalgia. Half of the participants (40) will receive the active treatment, while the other half (40) will receive a sham treatment. The allocation to either group will be randomized. Throughout the study period, both the caregivers and the participants will remain unaware of their assigned groups until the study conclusion. Participants' symptoms will be documented and their blood and stool will be tested for changes in certain metabolites. If this treatment works, it could be a significant breakthrough in managing fibromyalgia and might provide new insights into its causes.

**Detailed Description:** A double-blind, randomized placebo-controlled study to test the therapeutic potential of encapsulated oral fecal microbiota transplantation (FMT) from healthy donors to humans with fibromyalgia.

Fibromyalgia, a chronic and debilitating syndrome characterized by widespread pain, fatigue, sleep disturbances, and cognitive dysfunction poses a significant clinical, social, and economic burden globally, with limited targeted treatment options available. Recent studies have shed light on the potential role of the gut microbiome in fibromyalgia pathogenesis, highlighting alterations in gut microbiome composition correlated with clinical indices of the syndrome. Building upon this knowledge, the study seeks to explore the therapeutic potential of FMT, a well-established treatment increasingly investigated across various medical conditions. Preclinical investigations in mice have shown that FMT from fibromyalgia patients induces symptoms of the syndrome, while FMT from healthy controls reverses them. Encouragingly, preliminary results from an open-label pilot clinical trial involving fibromyalgia patients receiving encapsulated oral FMT from healthy donors demonstrated significant improvements in pain intensity, symptomatic burden, and quality of life measures, with favorable safety profiles. Based on these promising findings, a prospective randomized, controlled double-blind study is proposed to further evaluate the efficacy and safety of encapsulated oral FMT from healthy individuals in fibromyalgia patients. Clinical outcomes, as well as stool and serum samples, will be extensively characterized to elucidate the mechanisms underlying the effects of FMT, including its modulation of gut microbiome composition and function. The hypotheses involve expecting clinically significant improvements in pain and other symptoms of fibromyalgia following FMT, alongside corresponding alterations in gut microbiome composition and metabolomics profiles. This study aims to contribute valuable insights into the potential role of FMT as a novel therapeutic approach for fibromyalgia, addressing an unmet need in the management of this challenging condition.

### Conditions Module

**Conditions:**

- Fibromyalgia

**Keywords:**

- Fibromyalgia

- Fecal Microbiome Transplantation (FMT)

- Microbiome

- Chronic Pain

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** A Double-Blinded, Randomized Placebo-Controlled Trial

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants in this arm will receive a total of 5 real FMT treatments administered weekly, followed by an additional 5 maintenance FMT treatments on a monthly basis. The first induction treatment will consist of 30 grams, with subsequent treatments comprising 15 grams each.

**Intervention Names:**

- Other: Fecal Microbiome Transplantation

**Label:** Active Treatment - FMT

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Participants in this arm will receive a total of 5 sham FMT treatments administered weekly, followed by an additional 5 maintenance sham FMT treatments on a monthly basis. The first induction treatment will consist of 30 grams, with subsequent treatments comprising 15 grams each.

**Intervention Names:**

- Other: Sham Fecal Microbiome Transplantation

**Label:** Sham Treatment - FMT

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Active Treatment - FMT

**Description:** Healthy donor fecal microbiome transplantation, following depletion of the endogenous microbial communities using antibiotics and bowel cleansing

**Name:** Fecal Microbiome Transplantation

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Sham Treatment - FMT

**Description:** Capsules containing preservative solution only, following depletion of the endogenous microbial communities using antibiotics and bowel cleansing

**Name:** Sham Fecal Microbiome Transplantation

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Pain intensity will be assessed using the Visual Analogue Scale (VAS), with a score of zero indicating no pain and a score of 10 representing the worst possible pain.

**Measure:** Pain intensity at week five post-transplantation

**Time Frame:** Week five post transplantation induction

#### Secondary Outcomes

**Description:** As measured using the Fibromyalgia Impact Questionnaire (range 0-100, higher scores indicate worse symptoms)

**Measure:** overall symptomatic burden

**Time Frame:** Week five post transplantation induction and then on months 1, 3, 6 after last FMT

**Description:** As assessed by the Hospital Anxiety and Depression Scale questionnaire (range 0-21 for each of the domains, higher scores indicate worse symptoms)

**Measure:** Anxiety and depression

**Time Frame:** Week five post transplantation induction and then on months 1, 3, 6 after last FMT

**Description:** As assessed by the Pittsburgh Sleep Quality Inventory (range 0-21, higher scores indicate worse sleep quality).

**Measure:** Sleep quality

**Time Frame:** Week five post transplantation induction and then on months 1, 3, 6 after last FMT

**Description:** Pressure, heat and cold pain thresholds (Kg/cm\^2, degrees C respectively, lower thresholds indicate increased pain sensitivity)

**Measure:** Quantitative Sensory Testing

**Time Frame:** Week five post transplantation induction and then on months 1, 3, 6 after last FMT

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Adult women aged 18-75 years.
2. Diagnosis of fibromyalgia confirmed according to the 2016 diagnostic criteria by a pain physician who is a part of the study team.
3. An average reported pain of 6 or above during the preceding week.
4. Has remained symptomatic despite receiving standard care for fibromyalgia.

Exclusion Criteria:

1. Any active inflammatory condition (rheumatic, gastrointestinal or other).
2. Malignant neoplasm in the preceding 5 years.
3. Immunosuppression due to medical condition or treatment.
4. Uncontrolled psychiatric pathology.
5. Any other clinically important condition at the discretion of the investigator.
6. Known allergy to the antibiotics or laxatives used in the preparation protocol, or severe food allergy.
7. Active infection or expected antibiotic treatment in the upcoming 3 months after inclusion.
8. Pregnancy or intention to conceive.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Haifa

**Country:** Israel

**Facility:** Rambam Health Care Campus

**State:** North

**Zip:** 3109601

#### Overall Officials

**Official 1:**

**Affiliation:** Rambam Health Care Campus

**Name:** Amir Minerbi, MD-PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000012216

- Term: Rheumatic Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M29442

- Name: Chronic Pain

- Relevance: LOW

- As Found: Unknown

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M8486

- Name: Fibromyalgia

- Relevance: HIGH

- As Found: Fibromyalgia

- ID: M12161

- Name: Myofascial Pain Syndromes

- Relevance: HIGH

- As Found: Fibromyalgia

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005356

- Term: Fibromyalgia

- ID: D000009209

- Term: Myofascial Pain Syndromes

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

### Intervention Browse Module - Browse Leaves

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
