The Comeback Study

NCT03691987 | Completed Phase 2 DMC

• 1 other identifier: 2018/180
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center stratified (on gender and donor), block randomized, placebo-controlled, parallel group trial with 12-months follow-up of 80 chronic fatigue syndrome/encephalomyelitis (CFS/ME) participants. Participants will be randomized to treatment by preprocessed thawed donor fecal microbiota transplant or preprocessed thawed autologous fecal microbiota transplant. Primary endpoint is the efficacy of FMT at three months by the Fatigue Severity Scale. The investigators will use patient reported outcomes for primary and secondary outcome measures. Previous studies suggest that a dysbiosis of the gut microbiota may be a key feature in CFS/ME. We hypothesize that A: CFS/ME is caused by a dysbiosis in the gut flora causing barrier leakage of bacterial products, a low grade systemic immune activation and disturbances in the host energy metabolism. B: Recovery of a normal gut flora by fecal microbiota transplantation (FMT) alleviates symptoms and may even induce remission of CFS/ME. This project aims to determine if there is a true cause and effect relationship between a dysbiotic gut flora and CFS/ME by testing if treatment of the observed dysbiosis by FMT also can resolve CFS/ME symptoms. In this process, collection of blood, fecal, and urine samples before and after FMT will open the possibility to explore the relationship between the gut flora, immune response, host energy metabolism and CFS/ME using technologies of microbiomics, metabolomics and immunological characterizations for a better understanding of the pathobiology of CFS/ME.

Conditions

Chronic Fatigue Syndrome; Myalgic Encephalomyelitis

Keywords

fecal transplantation; bacterio therapy; fatigue; fecal microbiota transplantation

Outcome Measures

Primary Outcomes (1)

• Proportion with treatment success in FSS score in donor versus placebo FMT group. Treatment success is defined as an improvement of more than 1.2 points on the Fatigue Severity Scale (FSS)

  Fatigue Severity Scale (FSS) is a self-reported, 9-item fatigue scale. Participants rate all 9 items on a 7-point Likert scale (1-2-3-4-5-6-7) depending on how appropriate they felt the statement applied to them over the preceding week. The total score is calculated by adding up the answer from each item and divide by 9. Lower scores indicate better outcomes. Maximum score is 7. In an intention to treat analysis we will categorize participants as responders/non-responders, defining responders as decrease of more than 1,2 to the total baseline score in the FSS at 3 months post FMT by Chi Square. Baseline score will be the average of the two scores from the screening period. Missing values will be regarded as non responders

  Three months after treatment

Secondary Outcomes (9)

• Change in donor versus placebo FMT group in fatigue by the Fatigue Severity Scale score

  Change in Fatigue severity scale by repeated measures from baseline and until 1, 3, 6, 9 and 12 months after treatment

• Change in donor versus placebo FMT group in quality of life by the SF36 score

  Change in SF36 score by repeated measures from baseline and until 3 and 12 months after treamtent

• Change in donor versus placebo FMT group in neurocognitive function by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score from baseline and until 3 months after treatment.

  Change from baseline and until three months after treatment

• Change in donor versus placebo FMT group in anxiety and depression by the Hospital Anxiety Depression Scale (HADS) score

  Change in HADS score by repeated measures from baseline and until 3 and 12 months after treatment

• Change in donor versus placebo FMT group in gastrointestinal related complaints by the sum score of selected items in the DePaul Questionnaire (DPQ) (29, 30, 46 and 47)

  Change in DPQ score by repeated measures from baseline and until 6 and 12 months after treatment

Other Outcomes (10)

• Engraftment of donor microbiota

  3 months after FMT

• Engraftment of donor microbiota

  12 months after FMT

• Difference in metagenomic profile between responders and non responder to FMT

  Baseline samples before FMT

Study Arms (2)

Preprocessed thawed donor FMT

EXPERIMENTAL

The active transplants are processed in a 2-3 weeks period before treatment of the first participant. Fifty to eighty grams of freshly delivered feces from donors is mixed with 100 mL isotonic saline and 25 mL 85% glycerol, homogenized and poured through a 0.5 mm mesh steel strainer, and transferred to 60 ml luerlock syringes and stored at -40°C. Frozen transplants are slowly thawed 2 hours prior to administration by transferring the FMT-syringes to a waterbath (+30°C). The transplant is then mixed with 125 mL 12°C isotonic saline in an enema bag prior to installation.

Biological: Preprocessed thawed donor FMT

Preprocessed thawed autologous FMT

PLACEBO COMPARATOR

The placebo transplant from each participant is prepared during the inclusion process four to six weeks before intervention and stored at -40°C. Fifty to eighty grams of freshly delivered feces from participants is mixed with 100 mL isotonic saline and 25 mL 85% glycerol is homogenized and poured through a 0.5 mm mesh steel strainer, and transferred to 60ml Luerlock syringes. Frozen transplants are slowly thawed 2 hours prior to administration by transferring the Luerlock syringes to a waterbath (+30°C). The transplant is then mixed with 125 mL 12°C isotonic saline in the enema bag prior to installation.

Biological: Preprocessed thawed autologous FMT

Interventions

Preprocessed thawed donor FMT BIOLOGICAL

Delivered as an enema using the same equipment and technique as X-ray of the colon

Preprocessed thawed donor FMT

Preprocessed thawed autologous FMT BIOLOGICAL

Delivered as an enema using the same equipment and technique as X-ray of the colon

Preprocessed thawed autologous FMT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• International Consensus Criteria for CFS/ME
• years
• Mild-severe CFS/ME
• Fatigue Severity Scale score of 5,0-7,0
• Symptom duration for 2-15 years

You may not qualify if:

• Kidney failure
• Congestive heart failure
• Immuno-deficiency or use of immune-suppresive drugs
• Other disease that may explain ME/CFS symptoms discovered during diagnostic work up
• Use of antibiotics the last three months,
• Use of low dose naltrexone or Isoprinosin
• Pregnancy or breastfeeding
• Serious endogenous depression
• Chronic infectious disease (HIV, hepatitis B or C etc.)
• Introduction of new food supplements, change in diet or introduction of new medications the last three months
• Assessed not be able to follow the instructions for data and sample collection
• Very severe ME/CFS (WHO class IV)
• Symptom duration of less than 24 months or more than 15 years
• History of abdominal surgery, with the exception of appendectomy, cholecystectomy, caesarean section and hysterectomy
• Previous treatment with FMT

Sponsors & Collaborators

• University Hospital of North Norway: lead
• The Research Council of Norway: collaborator
• Quadram Institute Bioscience: collaborator
• Umeå University: collaborator
• Cornell University: collaborator

Study Sites (1)

University Hospital of North Norway, Harstad

Harstad, Troms, 9406, Norway

Location

Related Publications (1)

• Skjevling L, Goll R, Hanssen HM, Johnsen PH. Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): protocol for a 12-month randomised double-blind placebo-controlled trial. BMJ Open. 2024 Jun 10;14(6):e073275. doi: 10.1136/bmjopen-2023-073275.

  PMID: 38858151 DERIVED

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Fatigue

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Rasmus Goll, MD. PhD.

  University Hospital of North Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: October 2, 2018
• Study Start: February 15, 2019
• Primary Completion: March 1, 2023
• Study Completion: December 31, 2023
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Available when findings from primary and secondary endpoints are published. Study protocol will be available upon request when we initiate the inclusion.
• Access Criteria: Data access requests will be reviewed by study investigators. Requestors will be required to sign a Data Access Agreement

Locations

NO (1)