2023-505469-95-00招募中3 期
Fecal microbiota transplantation for primary sclerosing cholangitis - randomized study versus sham transplantation (FMT-SCLER).
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 11
- 主要终点
- Proportion of success at week 48. Success is defined as patients with serum ALP <1.3 ULN at week 48 and a reduction of, at least 15%, compared to baseline ALP level AND total bilirubin ≤ 1 ULN at week 48
研究概览
简要总结
To assess in patients with PSC the efficacy of FMT versus sham transplantation on ALP and bilirubin at week 48 (surrogate markers of transplantation-free survival in PSC patients) in addition to standard UDCA therapy.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Males or females
- •Subject affiliated to the French Social Security System
- •Age ≥18 and ≤75 years
- •Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC
- •IBD diagnosed according to international guidelines (presence of endoscopic and histologic signs)
- •IBD inactive for at least 6 months (defined by no evidence of flare and no change in treatment)
- •ALP ≥ 1.3 ULN (at least 2 times within a 3 months pre-inclusion period) or elevated total bilirubin ≤50mol/l (with concomitant elevated direct bilirubin).
- •Treatment with UDCA (13-23 mg/kg/d) for at least 6 months and at the same dosage for at least 3 months
- •Using contraceptive in women of childbearing potential. Women of childbearing potential, i.e. fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply a highly effective method of birth control with a low failure rate (i.e. less than 1% per year) when used constantly and correctly.
- •Written informed consent signed
排除标准
- •Small duct PSC
- •History of acute cholangitis in the last 3 months prior to inclusion or current acute cholangitis
- •HIV infection
- •Prior liver transplantation
- •Endoscopic treatment for bile duct stenosis ≤ 3 months prior to inclusion or planned within 3 months post randomization date
- •History of or established or suspected hepatobiliary carcinoma.
- •Any severe comorbidity that may reduce life expectancy
- •History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to inclusion)
- •Dosage changes of treatment for liver disease in the last 3 months or new treatment for liver disease started in the last 3 months
- •History of colorectal carcinoma or high-grade dypsplasia in previous screening colonoscopy
- •History of total colectomy
- •Autoimmune hepatitis defined by the presence of moderate to severe interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: AST or ALT > 5 ULN, Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
- •Current active IBD defined by a partial Mayo score > 2 in patients with ulcerative colitis (UC), unclassed colitis or a Crohn’s Disease Activity Index (CDAI) > 150 in patients with Crohn’s disease
- •Changes in IBD treatment or initiation of a new treatment for IBD in the last 3 months
- •Current treatment with biologics (anti-TNF agent, vedolizumab, ustekinumab) or JAK inhibitors (tofacitinnib) or prednisone > 10 mg/day or budesonide > 3 mg /day) (or treatment initiated less than one month)
- •Any contra-indication to swallow capsules
- •Renal insufficiency (clearance<60 ml/min)
- •Unable to consent, subject to legal or administrative decision (protection measure or deprivation of liberty) or involuntary psychiatric care.
- •Inclusion in another clinical trial on medicinal products, clinical investigation protocol concerning a medical device or interventional protocol not concerning a health product, or in the exclusion period any other interventional study
- •Pregnancy or desire for pregnancy or breastfeeding
- •Secondary sclerosing cholangitis (notably IgG4-associated cholangitis)
- •Cirrhosis defined by Liver elastometry >14.4 kPa or by current or past decompensation of cirrhosis
- •AST or ALT > 7 ULN in the last 3 months
- •Platelets count in the last 3 months < 100 000/mm3
- •Albumin in the last 3 months <35g/L
- •Prothrombin index in the last 3 months < 70%
- •Hepatic comorbidity: HBV infection (defined by positive Ag HBS), HCV infection (defined by positive HCV RNA), alcohol abuse (defined by alcohol intake > 30g/day), metabolic dysfunction associated steatohepatitis, primary biliary cholangitis, Hemochromatosis, Wilson disease, α1-antitrypsin deficiency, celiac disease
结局指标
主要结局
Proportion of success at week 48. Success is defined as patients with serum ALP <1.3 ULN at week 48 and a reduction of, at least 15%, compared to baseline ALP level AND total bilirubin ≤ 1 ULN at week 48
Proportion of success at week 48. Success is defined as patients with serum ALP <1.3 ULN at week 48 and a reduction of, at least 15%, compared to baseline ALP level AND total bilirubin ≤ 1 ULN at week 48
次要结局
- Proportion of patients with serum ALP <1.3 ULN and a reduction of at least 15% compared to baseline ALP level at week 12 24 36 and 48
- Proportion of patients that normalized total bilirubin at week 12 ,24 36 and 48 (total bilirubin <1 ULN)
- Proportion of patients that normalized ALP at week 12 24 36 and 48 (ALP <1 ULN)
- Proportion of patients that normalized all liver tests (ALP <1ULN and GGT <1 ULN and AST <1 ULN and ALT <1 ULN and total bilirubin <1 ULN) at week 12 24 36 and 48
- Change in Elastometry between week 0 and week 48
- PSC Prognostic scores including the MELD score, the Revised PSC Mayo Risk Score, the Amsterdam-Oxford prognostic model (week 0, week 24, week 48)
- Safety endpoints: - Percentage of patients with clinical (including infectious events and increased IBD activity) or biological adverse events (leucocytes, CRP) during the study period (overall and between randomization and week 48, between randomization and week 104) - Survival rate without liver events (decompensation of cirrhosis, acute cholangitis, jaundice, need for ERCP) at week 48
- Pruritus (VAS and 5D pruritus scale) at week 0, 12, 24, 36 and 48
- Symptoms and quality of life (PRO-CSP questionnaire, QMCF questionnaire – Questionnaire de la maladie chronique du foie) and fatigue (PBC 40 questionnaire) : at week 0, week 24 and week 48
- Bile acids measured by chromatography at week 0, week 48
- Cholangiographic abnormalities, assessed by magnetic resonance cholangiography at week 0, week 48
- Changes in IBD activity: clinical score between week 0 and week 48 (HBI and Crohn’s disease Activity Index [CDAI] for Crohn’s disease and Mayo score for Ulcerative colitis), fecal calprotectin and endoscopic score assessed by colonoscopy (Crohn’s disease Endoscopic Index of Severity [CDEIS] for Crohn’s disease and ulcerative colitis Endoscopic Index of Severity [UCEIS] for ulcerative colitis).
- Analysis of gut microbiota at week 0, 12, 24, 36 and 48.
研究者
stanislas quenard
Scientific
Assistance Publique Hopitaux De Paris
研究点 (11)
Loading locations...
相似试验
已完成
2 期
Fecal Microbiota Transplantation for PancreatitisIntestinal Bacteria Flora DisturbanceIntestinal DysfunctionFecal Microbiota TransplantationAcute PancreatitisNCT02318134The First Affiliated Hospital of Nanchang University60
招募中
2 期
A-FMT for active UCMild to moderate ulcerative colitisUlcerative colitisJPRN-jRCTs031220542agahara Akihito37
已完成
不适用
Fecal microbiota transplantation for recurrent Clostridioides difficile infectioRecurrent Clostridioides difficile infectionJPRN-UMIN000042418Shiga University of Medical Science
进行中（未招募）
2 期
FMT for recurrent CDIRecurrent Clostridioides difficile infectionPseudomembranous colitis, Clostridium difficileD004761JPRN-jRCTs051190048Andoh Akira23
招募中
2 期
Fecal Microbiota Transplantation for Parkinson*s Disease: a pilot studyParkinson's diseaseParkinson disease10028037NL-OMON52432eids Universitair Medisch Centrum16