The Comeback Study
Fjalë kyçe
Abstrakt
Përshkrim
CFS/ME participants:
General practitioners recruit participants from the local area, by posters at the doctors' offices. In addition the study has a facebook site, named "the COMEBACK study", where interested CFS/ME subjects can submit their interest to be assessed for participation. After a telephone screening of potential participants by the Canada Criteria and CFS/ME severity rating, eligible subjects will be referred to department of physical medicine and rehabilitation UNN Harstad (FYSMED) and re-assessed. During this screening process the investigators will keep a track record of screening failures noting reason for failure. Participants will have a physical exam and necessary workup including blood, fecal and urine tests to exclude differential diagnosis according to the Norwegian National Guidelines for Assessment of CFS/ME. Participants receive information about the study and give their written consent. Subjects earlier diagnosed with CFS/ME at FYSMED will undertake the same re-assessment.
During the work up, participants will do the Fatigue Severity Scale, Hospital Anxiety and Depression scale, SF 36, Modified DePaul Questionnaire, the Rome IV criteria for irritable bowel syndrome, and the "Repeatable Battery for the Assessment of Neuropsychological Status" test (RBANS).
Donors are recruited informally from the local high schools. Donors are included and screened according to the European Consensus Guidelines from 2017. The full screening will be undertaken before the first feces donation and every 4th week. The inclusion and screening will be performed at the department of physical medicine and rehabilitation UNN Harstad. The investigators will keep a track record of screening failures noting reason for failure.
Participants receive FMT at the gastroenterology outpatient clinic at University Hospital of North Norway Harstad, Norway. No antibiotics are given prior to the intervention. The participants must do a bowel lavage using Sodiumpicosulphate/Magnesiumcitrate (Picoprep, Ferring) before intervention. The treatment will be administered by enema. Active treatment will be pre-processed frozen donor feces. Placebo will be the participant's own feces processed and frozen during the study inclusion. After the intervention, the participants have no restrictions on activity level and are asked to keep an unchanged diet without introduction of any new food supplements or probiotics in the follow up period. To keep track of change in diet investigators ask participants to do a food frequency questionnaire before the FMT and at 3 and 12 months after the intervention. Use of antibiotics, food supplement and use of medications will also be recorded.
The treatment will take place in blocks of four consecutive participants per day. A data engineer at the Department of Clinical Research at the University Hospital of North Norway, Tromsø (UNN,Tromsø) creates the allocation sequence using the REDCap software. The treatment is randomized on donor and placebo in fixed blocks of 4 with 2 active (1 donor A and 1 donor B) and 2 placebo. Block allocation will be stratified on gender.
A stratification on donor and gender will be performed by assigning full blocks of male and female participants. In the two active slots in each block of four, one active slot will be used for donor A and one for donor B. The stratification of gender reflects the higher incidence of CFS/ME in women.
Allocation is done in solitude in a closed room with no transparency, only containing a freezer with the active transplants (tagged by donor batch ID) and the placebo transplants (tagged by screening number). Before allocation of treatment, an investigator places the FMT-placebos on a table in the room. A minimum of four participants is allocated to treatment each time. The allocator can then enter the room as the researcher placing all the placebos leaves the room. The allocator will access the randomization sequence when entering participants screening number on the REDCap software using a computer in the same room. The allocator will be the only person involved in the study that can access the randomization program at the REDCap software. If a screening number is randomized to active treatment, the allocator removes the tag from the placebo and places it on a donor FMT treatment instead. All unused placebo transplants will be disposed immediately. When finished, the allocator places the allocated treatment in a box in a designated freezer. The allocator will build a key file matching the active treatment to the donor batch id by updating a key file on paper and store it in a safe not accessible to any others. In addition the allocator will write the corresponding patient screeningnumber on tags from the used donor batch and keep them as backup in the same safe. This will allow for tracking of each individual donor batch to a corresponding participant at the end of trial when all follow up is complete.
Datat
| Verifikuar së fundmi: | 01/31/2019 |
| Paraqitur së pari: | 09/09/2018 |
| Regjistrimi i vlerësuar u dorëzua: | 09/26/2018 |
| Postuar së pari: | 10/01/2018 |
| Përditësimi i fundit i paraqitur: | 02/14/2019 |
| Përditësimi i fundit i postuar: | 02/18/2019 |
| Data e fillimit të studimit aktual: | 02/14/2019 |
| Data e vlerësuar e përfundimit primar: | 01/31/2020 |
| Data e vlerësimit të përfundimit të studimit: | 12/30/2023 |
Gjendja ose sëmundja
Ndërhyrja / trajtimi
Biological: Preprocessed thawed donor FMT
Biological: Preprocessed thawed autologous FMT
Faza
Grupet e krahëve
| Krah | Ndërhyrja / trajtimi |
|---|---|
| Experimental: Preprocessed thawed donor FMT 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 Delivered as an enema using the same equipment and technique as X-ray of the colon |
| Placebo Comparator: Preprocessed thawed autologous FMT 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 Delivered as an enema using the same equipment and technique as X-ray of the colon |
Kriteret e pranimit
| Moshat e pranueshme për studim | 18 Years Për të 18 Years |
| Gjinitë e pranueshme për studim | All |
| Pranon Vullnetarë të Shëndetshëm | po |
| Kriteret | FMT PARTICIPANTS Inclusion Criteria: - Canada Criteria (2011) - 18-65 years - Mild-severe CFS/ME - Fatigue Severity Scale score of 5,0-7,0 - Symptom duration for 2-15 years Exclusion Criteria: - 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, 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 FMT DONORS Inclusion criteria: - Healthy - Age 16-30 years - Type 3 or 4 stool by the Bristol Stool Scale Exclusion criteria: - Use of peroral antibiotics past 3 months - Use of topical antibiotics past 2 months - Tattoo or piercing past 6 months - Former imprisonment - History of: -chronic diarrhea - constipation - inflammatory bowel disease - colorectal polyps - colorectal cancer - immuno-suppression - Obesity - Metabolic syndrome - Atopic skin disease - CFS/ME - Psychiatric disorders - Other serious autoimmune disease - Close relatives with serious autoimmune disease - High risk sexual behavior - Bowel movements that does not correspond to a Bristol Stool Scale type 3 or 4 - Journeys abroad the last six months to countries high in antibiotic resistance - Use of food supplements, pre-, -pro, -or symbiotics past one month - Dysbiosis grade 3 or more by the GA dysbiosis test |
Rezultati
Masat Kryesore të Rezultateve
1. Change in individual global Fatigue Severity Scale score. [Proportion of participants with change from baseline in global Fatigue Severity Scale score at 3 months after FMT]
Masat dytësore të rezultateve
1. Change in individual global Fatigue Severity Scale score. [Proportion of participants with change from baseline in global Fatigue Severity Scale score at 12 months after FMT]
2. Change in individual global Fatigue Severity Scale score by repeated measures [Change in Fatigue severity scale by repeated measures from baseline, 1, 3, 6, 9 and 12 months]
3. Change in global score by the SF36. [Change from baseline global SF36 Score at 3 months after FMT]
4. Change in subscale score by the SF36. [Change from baseline in subscale SF36 Score at 3 months after FMT]
5. Change in global score by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Change from baseline in global RBANS score at 3 months after FMT]
6. Change in subscale score by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Change from baseline in subscale RBANS score at 3 months after FMT]
7. Change in global score by the Hospital Anxiety Depression Scale (HADS) [Change from baseline in global HADS score at 3 months after FMT]
8. Change in subscale score by the Hospital Anxiety Depression Scale (HADS) [Change from baseline in subscale HADS score at 12 months after FMT]
9. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [Baseline to end of follow up at 12 months after FMT]
Masat e tjera të rezultateve
1. Engraftment of donor microbiota [3 months after FMT]
2. Engraftment of donor microbiota [12 months after FMT]
3. Difference in metagenomic profile between responders and non responder to FMT [Baseline samples before FMT]
4. Change in the nature of host immune and antibody response [Change from baseline to 3 months and difference between responders and non-responders to treatment at 3 months]
5. Change in the nature of host immune and antibody response [Change from baseline to 12 months and difference between responders and non-responders to treatment at 12 months]
6. Difference in the nature of host immune and antibody response between responders and non responders to FMT [Baseline samples before FMT]
7. Change in the metabolome in feces, blood and urine [Change from baseline to 3 months and difference between responders and non-responders to treatment at 3 months]
8. Change in biomarkers for breach in gut epithelium (sLPS-binding protein and sCD14) before and after transplantation [Change from baseline to 3 months and difference between responders and non-responders to treatment at 3 months]
9. Change in biomarkers for breach in gut epithelium (sLPS-binding protein and sCD14) before and after transplantation [Change from baseline to 12 months and difference between responders and non-responders to treatment at 12 months]
10. Difference in biomarkers for breach in gut epithelium (sLPS-binding protein and sCD14) in responders and non responders to FMT [Baseline samples before FMT]
