7.2 Plenary Report Edmonton FMT RCT Kao · 2016. 9. 10. · Edmonton$FMT$Program$ • Oct2012$ •...
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FMT Report from Edmonton Dina Kao Edmonton FMT Program University of Alberta
Transcript of 7.2 Plenary Report Edmonton FMT RCT Kao · 2016. 9. 10. · Edmonton$FMT$Program$ • Oct2012$ •...
FMT Report from Edmonton
Dina Kao Edmonton FMT Program
University of Alberta
Edmonton FMT Program
• Oct 2012 • 106 paCents with RCDI (open label) – Success rate • 85% with one infusion • 96% with two infusions
• 3 universal stool donors
ObjecCves
• To review ongoing FMT trials in Edmonton • To review preliminary results from these trials
FMT trials
• RCT for recurrent Clostridium difficile infecCon – Colonoscopy vs capsule delivery
• Open label trials: – UlceraCve coliCs – Crohn’s coliCs – HepaCc encephalopathy – Obesity and metabolic syndrome
RCDI
• MulCcenter RCT (Edmonton & Calgary) – FMT by colonoscopy vs oral capsules (1:1)
• At least 3 episodes of CDI • StraCfied by age (<65 vs. > 65)and immune status (normal vs. immunocompromised)
• N=200 • Funded by Alberta Health Services
RCDI
• Outcomes of interest – Cure rate – Changes in microbial composiCon by metagenomics
– Predictors of success/failure • Keystone species
– Bile acid metabolism – Cost analysis – PaCent preference
RCDI in Crohn’s coliCs
1st FMT 3rd FMT (6.5 months later)
RCDI and UC
1st FMT 2nd FMT (3.5 months later)
Open label FMT for Crohn’s
Inclusion • Age >18 and < 65 • Dx colonic or ileocolonic
Crohn’s • Mild to moderate HBI 5-‐16 • Failed 5 ASA or
immunosupressant > 3 mo • AcCve colonic inflammaCon
(2/3) – CRP >8 mg/L – FC >250 ug/g – SES-‐CD 4-‐19
Exclusion
• Ileocecal resecCon • Pregnancy/breasceeding • Exposure to a biologic • AcCve perianal disease • AcCve infecCon • Allergy to cirpo and flagyl • Dysplasia
FC= fecal calprotecCn; SES-‐CD= simple endoscopic score for Crohn's disease
Open label FMT for UC
Inclusion • Age >18 and < 65 • Mild to moderate UC-‐
parCal Mayo 2-‐6 • Failed 5ASA or
immunosuppressant > 3 months
• AcCve colonic inflammaCon (2/3) – CRP >8 mg/L – FC >250 ug/g – Mayo endo score 1-‐2
Exclusion
• ProcCCs • Colectomy or diverCng
ileostomy
• Pregnancy/breasceeding • Exposure to a biologic • AcCve infecCon • Allergy to cirpo and flagyl • Dysplasia
Trial design
Week 0
Week 2
Week 4
Week 6
Week 8
Cipro/flagyl x 5 d
Washout 24 hours F/U Week 10
F/U Week 12
F/U Week 1
Outcomes of interest
• Clinical and endoscopic improvement • Fecal and mucosa associated microbial analyses
• Cytokine profile in serum and mucosa
• Bile acid and short chain fahy acid metabolism
• MutaCon
FMT in IBD
Before FMT 4 weeks post FMT
Kao D, Hohe N, & Madsen, K. JCG 2014.
Kao D, Hohe N, & Madsen, K. JCG 2014.
Ileocolonic Crohn’s CRP FC endo score HBI score
Screening 22.6 5235 5
Week 0 FMT #1 (colonoscopy) 23
Day 1 14.9 no stool
Week 1 11.1 1792 1
Week 2 FMT #2 (enema) 18.1 3815 0
Week 4 FMT #3 (colonoscopy) 12.2 1608 13 2
Week 6 FMT #4 (enema) 11.8 3090 0
Week 8 FMT #5 (colonoscopy) 18.4 8110 9 0
Week 10 8.7 2289 0
Week 12
Rectum
8/8/14 10/3/14
Transverse colon
8/8/14 10/3/14
Cecum
8/8/14 10/3/14
TI
8/8/14 10/3/14
UC #1 CRP FC endo score Mayo score
screening 10.1 948 3
Week 0 FMT #1 (colonoscopy) 1
Day 1 d 1.4
Week 1 1 800 0
Week 2 FMT #2 (enema) 1.1 1
Week 4 FMT #3 (colonoscopy) 3.3 917 1-‐2 1
Week 6 FMT #4 (enema) 1.7 3489 2
Week 8 FMT #5 (colonoscopy) 2.1 3075 1-‐2 1
Week 10 5.3 2898
Week 12 FMT #1‘ (colonoscopy) 4.8 1-‐2 1
Week 13 3.7 1100 0
UC #2 CRP FC endo score Mayo score
Screening 26.7 >9000 5
Week 0 FMT #1 (colonoscopy) 2
Day 1 12.7
Week 1 0.9 680 0
Week 2 FMT #2 (enema) 0.7 324 1
Week 3 43.4 3
Week 4 323.2
Week 4 + 1 day (hospitalizaCon) 368.1
Week 4 + 3 days (discharge) 31.2
Conclusion
• FMT appears to be a promising alternaCve for some IBD paCents – Clinical response/remission can be seen in 1 week – Response cannot be predicted – Possibility of IBD flare?
• More research is needed – Which paCent? – When? – Donor screening/selecCon? – Mechanisms of acCon?
Personalized medicine
