DOCSLIB.ORG

Fecal Microbiota Transplantation (FMT) for C

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fecal Microbiota Transplantation (FMT) for C Fecal Microbiota Transplantation (FMT) For C. difficile Infection (CDI) in Solid Organ Transplant (SOT) Recipients Protocol Number: 2018-1056 National Clinical Trial (NCT) Identified Number: NCT03617445 Principal Investigator & IND Sponsor: Nasia Safdar, MD, PhD Funded by: NIAID Version Number: 5 Date: 05 January 2021 This document is confidential. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the Sponsor or Principal Investigator. RECOVER PI: N. Safdar PROTOCOL VERSION HISTORY Version Date Comment 1.0 13AUG2018 Initial version 1.1 29AUG2018 Amendment per FDA 2.0 24Jul2019 Amendment per FDA and Steering Committee 3.0 12Mar2020 Amendment 4.0 24Aug2020 Amendment 5.0 05Jan2021 Amendment – FMT route of administration Version 5 05 January 2021 Page 2 of 86 RECOVER PI: N. Safdar TABLE OF CONTENTS 1.0 STATEMENT OF COMPLIANCE .............................................................................................................5 2.0 LIST OF ABBREVIATIONS .....................................................................................................................6 3.0 TERMINOLOGY .......................................................................................................................................7 4.0 STUDY SUMMARY ..................................................................................................................................7 Schematic of Study Design ........................................................................................................................... 9 5.0 KEY PERSONNEL .................................................................................................................................10 6.0 INTRODUCTION ....................................................................................................................................12 Background ................................................................................................................................................. 12 Rationale ..................................................................................................................................................... 12 7.0 STUDY OBJECTIVES AND ENDPOINTS .............................................................................................14 Primary Objective ........................................................................................................................................ 14 Secondary Objectives ................................................................................................................................. 14 Primary Outcome Measure ......................................................................................................................... 16 Secondary Outcome Measures .................................................................................................................. 16 8.0 STUDY DESIGN .....................................................................................................................................20 General Design ........................................................................................................................................... 20 Rationale for Intervention ............................................................................................................................ 20 Study Risk/Benefit Assessment .................................................................................................................. 21 End of Study Definition................................................................................................................................ 22 9.0 SUBJECT SELECTION ..........................................................................................................................23 Inclusion/Exclusion Criteria ......................................................................................................................... 23 Recruitment ................................................................................................................................................. 24 Retention Strategies .................................................................................................................................... 24 Early Termination and Withdrawal .............................................................................................................. 24 10.0 STUDY INTERVENTION ........................................................................................................................25 Study Intervention Description .................................................................................................................... 25 Source ......................................................................................................................................................... 25 Packaging and Labeling .............................................................................................................................. 26 Preparation .................................................................................................................................................. 27 Storage and Stability ................................................................................................................................... 27 Accountability .............................................................................................................................................. 27 Dosing and Administration .......................................................................................................................... 28 Randomization and Blinding ....................................................................................................................... 28 Unblinding Procedures ................................................................................................................................ 28 Study Intervention Compliance ................................................................................................................... 28 Concomitant Therapy .................................................................................................................................. 29 11.0 STUDY VISITS AND PROCEDURES ....................................................................................................29 Screening and Enrollment ........................................................................................................................... 29 Visit 1 (Baseline) ......................................................................................................................................... 30 Visit 2 (Randomization) ............................................................................................................................... 30 Study Drug Administration Follow-up Call .................................................................................................. 31 Visit 3 (in-person) ........................................................................................................................................ 31 Visit 4 (in-person or phone call) .................................................................................................................. 31 Visit 5 (in-person or phone call) .................................................................................................................. 31 Version 5 05 January 2021 Page 3 of 86 RECOVER PI: N. Safdar Visit 6 (in-person or phone call) .................................................................................................................. 31 Visit 7 (in-person or phone call) .................................................................................................................. 32 Telephone Contact ...................................................................................................................................... 32 Unscheduled Visit ....................................................................................................................................... 32 Early Termination and Withdrawal .............................................................................................................. 32 Study Calendar ........................................................................................................................................... 34 Study Procedures ........................................................................................................................................ 36 12.0 DATA COLLECTION, HANDLING AND RECORD KEEPING ..............................................................38 Types of Data .............................................................................................................................................. 38 Data Collection ............................................................................................................................................ 38 Data Capture Methods ................................................................................................................................ 39 Data Confidentiality ..................................................................................................................................... 40 Records Retention .....................................................................................................................................
Load more

Recommended publications
  • Laparoscopic Hand-Sewn Duodenal Switch. Video
    Baltasar A., BMI-2012, 2.1.4 (11-13) February 2012 OA Laparoscopic Hand-sewn Duodenal Switch. Video Aniceto Baltasar, *Rafael Bou, Marcelo Bengochea, *Carlos Serra, *Nieves Pérez San Jorge Clinic and *Hospital “Virgen de los Lirios”. Cid 61.Alcoy. Alicante. Spain. Phone (0034) 965.332.536. [email protected] Key Words: Laparoscopic Duodenal Switch; Bilio Pancreatic Diversion; Gastric Sleeve; Obesity surgery Introduction The Duodenal Switch (DS) is one alternative to the Scopinaro Bilio-Pancreatic Diversion (BPD). Hess [1] performed the first open case in March 1988 (in a male BMI-60 and he was BMI-29 17 years later) and Marceau [2] made the first publication. Baltasar [3.4] increased the statistics. Rabkin [5] performed the first Fig.1. LapDS Fig.2. Ports positions Lap DS (LDS) hand-assisted for the duodeno-ileum anastomosis in August 1999, Gagner [6] the first fully LDS in September the same year and Baltasar [7.8] published the second world experience. Three surgeons perform the operation SA is in between the legs, SB in on the right side and SC on the LDS consist of 1) Vertical Gastric Sleeve (VGS) with right side through 6 ports. Direct vision approach is pyloric preservation of less than 60 cc and 2) A BPD always used for the first port (1P) with an Ethicon with a Common Channel (CC) of 65-100 cm, an Endopath#12 on the lateral border of the right rectus Alimentary Loop (AL) of 235-300 cm and the muscle, 3-4 fingerbreadths below the right costal remaining Bilio-Pancreatic Loop (BPL) as the margin.
    [Show full text]
  • Hybrid Procedure Offers a Less Invasive Alternative to Colectomy
    The better way to get better Hybrid procedure offers a less invasive alternative to colectomy Insufflation gas provides important advantage The colonoscopy-laparoscopy procedure is made possible through the combined skills of the gastroenterologist and laparoscopic surgeon, and the use of CO2 rather than ambient air for insufflation — the introduction of gas into the colon to improve visibility. CO2 is more quickly absorbed by the gastrointestinal tract and results in less bowel distension, giving the laparoscopic surgeon a better field of vision within the abdominal cavity. © Copyright Olympus. Used with permission. “Some patients who would have required a bowel resection can instead benefit from this A new, minimally invasive procedure that is a hybrid of colonoscopy and less invasive procedure. We’re laparoscopy is proving to be a safe and effective alternative to open colectomy using this combined technique (removal of part of the colon) for patients with benign colon polyps that are as a way for patients to avoid colectomy,” explains James not removable endoscopically. Yoo, M.D., a colorectal surgeon Patients who undergo this hybrid procedure experience less pain and often go at UCLA. “This procedure home after only one or two days. Scarring and wound complications are minimal involves tiny incisions for the as the laparoscopic surgeon makes only small, keyhole incisions in the abdomen laparoscopic instruments and patients stay in the hospital only rather than the long incision characteristic of a traditional colectomy. a day or two.” WWW.UCLAHEALTH.ORG 1-800-UCLA-MD1 (1-800-825-2631) Who can benefit from the procedure? Participating When a routine colonoscopy reveals polyps, they are usually removed at the Physicians time of the procedure as a precaution against their progression to cancer.
    [Show full text]
  • ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding
    nature publishing group PRACTICE GUIDELINES 1265 CME ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding L a u r e n B . G e r s o n , M D , M S c , F A C G1 , J e ff L. Fidler , MD 2 , D a v i d R . C a v e , M D , P h D , F A C G 3 a n d J o n a t h a n A . L e i g h t o n , M D , F A C G 4 Bleeding from the small intestine remains a relatively uncommon event, accounting for ~5–10% of all patients presenting with gastrointestinal (GI) bleeding. Given advances in small bowel imaging with video capsule endoscopy (VCE), deep enteroscopy, and radiographic imaging, the cause of bleeding in the small bowel can now be identifi ed in most patients. The term small bowel bleeding is therefore proposed as a replacement for the previous classifi cation of obscure GI bleeding (OGIB). We recommend that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identifi ed anywhere in the GI tract. A source of small bowel bleeding should be considered in patients with GI bleeding after performance of a normal upper and lower endoscopic examination. Second-look examinations using upper endoscopy, push enteroscopy, and/or colonoscopy can be performed if indicated before small bowel evaluation. VCE should be considered a fi rst-line procedure for small bowel investigation. Any method of deep enteroscopy can be used when endoscopic evaluation and therapy are required.
    [Show full text]
  • The Role of Growth Hormone in Adaptation to Massive Small Intestinal Resection in Rats
    0031-3998/01/4902-0189 PEDIATRIC RESEARCH Vol. 49, No. 2, 2001 Copyright © 2001 International Pediatric Research Foundation, Inc. Printed in U.S.A. The Role of Growth Hormone in Adaptation to Massive Small Intestinal Resection in Rats MICHAEL DURANT, SHARRON E. GARGOSKY, K. ANDERS DAHLSTROM, RIXUN FANG, BARRY H. HELLMAN, JR., AND RICARDO O. CASTILLO Department of Pediatrics [M.D., S.E.G., R.F., R.O.C.], Department of Pathology [B.H.H.], and the Digestive Disease Center [R.O.C.], Stanford University School of Medicine, Stanford, CA, U.S.A.; and Department of Pediatrics, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden [K.A.D.] ABSTRACT The residual small bowel undergoes profound adaptive alter- alterations in processing of digestive hydrolases of the distal ations after surgical resection. GH is considered to have a role in intestine, indicating that GH may have region-specific effects on regulation of these adaptive changes, but its precise role is small intestinal function. We conclude that GH is required for the unknown. We investigated the role of GH by studying the normal expression of specific components of the adaptive re- response to intestinal resection in rats with isolated GH defi- sponse to massive small intestinal resection, but not for all ciency. Spontaneous dwarf rats, a strain of rats with congenital aspects. The aspects that require GH appear to involve protein isolated GH deficiency, underwent 60% resection of the small synthesis and processing. (Pediatr Res 49: 189–196, 2001) intestine and parameters of the response of the intestinal remnant were compared with age-matched GH-deficient rats undergoing Abbreviations: transection, GH-normal rats undergoing 60% resection, and non- SDR, spontaneous dwarf rats manipulated GH-normal rats.
    [Show full text]
  • Fecal Microbiota Transplantation and Metagenomic Medicine
    FEATURE ARTICLE Fecal microbiota transplantation and metagenomic medicine Arthur Ling (Meds 2015) Faculty Reviewer: Dr. David Colby, MSc, MD, FRCPC (Departments of Microbiology and Immunology, Medi- cine and School of Dentistry) INTRODUCTION was in 1958, when a team of physicians in Colorado successfully treated four patients with pseudomembranous colitis.6 At the time, three of these Have you ever had a gut feeling that you were not alone? Before you get patients had severe life threatening post-operative colitis that was unre- up to lock the doors, consider that our gastrointestinal tract, in particular sponsive to conventional treatments. In a final attempt, the physicians the distal colon, is home to trillions of bacteria and other microorgan- pioneered the FMT procedure and the patients miraculously recovered isms collectively referred to as the microbiome. Fortunately, most of the and were discharged after several days. It would be much later in 1978 microbiota are not harmful, but instead provide physiological functions when C. difficile was identified to be a cause of antibiotic-associated such as digestion and immune system development. Importantly, the in- diarrhea/colitis, which was then followed by the first report of a success- testinal microbiome acts as a front line defense against potential patho- ful FMT in a CDI case in 1981.6,7 While FMT was originally performed gens entering our gut. An important clinical example that highlights this by a crude colonic retention enema of homogenized stool samples ob- is an infection by a bacterium called Clostridium difficile, which usu- tained from closely related or intimate donors, the procedure has been ally causes a diarrheal/colitis syndrome, but in some cases may progress refined through the 1990s.
    [Show full text]
  • Pharmacology of Obesity
    Malabsorptive Bariatric Procedures R-en-Y, and Biliopancreatic Diversion with the Duodenal Switch Dana Portenier, MD Assistant Professor of Surgery Division Chief, Metabolic and Weight Loss Surgery Chief, General Surgery, Duke Regional Hospital Duke University School of Medicine Disclosures No conflicts of interest Objectives Understand the main differences between R-en-Y and BPD/DS Describe the complications Discuss the development of robot assisted bariatric procedures Types of Obesity Surgery Gastric Restrictive – Lap band – Sleeve Gastrectomy Combined mode of action – Roux en Y Bypass – BPD – BPD/DS Roux-en-Y Gastric Bypass Surgical Difference BPD/DS Surgical differences Roux en Y BPD/DS Stomach pouch (15-30cc) Stomach pouch (150-250cc) Gastric outlet narrow Gastric outlet is unrestricted Pylorus non-functional Pylorus functional Less malabsorption More malabsorption Performed most commonly Less common laparoscopic More complex laparoscopically Life style differences Roux en Y BPD/DS Quantity and quality of food More normal more restricted Dumping more common Incidence very low Nausea and vomiting more Less common common Less frequent bowel More frequent bowel movements (q OD) movements (2-3/day) Less foul smelling More foul smelling Metabolic differences Roux en Y BPD/DS B12 and iron deficiency more Vit A and D deficiency common more common Oxalate stones less More Long term weight loss 60% of Weight loss 75% of EBW EBW Effective for DM Type 2 (84%), Very Effective for DM type less effective for 2 (98-99% resolution), hypercholesterolemia
    [Show full text]
  • Effect of Liver Transplantation on Inflammatory Bowel Disease In
    )(6{; 1 Effect of Liver Transplantation on Inflammatory Bowel ~ Disease in Patients With Primary Sclerosing Cholangitis I Igor DvorchikY Michael Subotin,l A. Jake Demetris,3 John]. Fung,3 Thomas E. Starzl,3 Samuel Wieand,2,4 I and Kareem M. Abll-Elmagd3 I This report investigates the influence ofliver transplantation and concomitant immunosup­ pression on the course of progression of inflammatory bowel disease (IBD) and discusses statistical methodology appropriate for such settings. The data on 303 patients who under­ went liver transplantation for primary sclerosing cholangitis (PSC) were analyzed using person-time analysis and Cox regression, with the duration ofIBD as the time variable and transplantation as a segmented time-dependent covariate, to take into account both post­ transplant and pretransplant history of IBO. The need for colectomy and appearance of colorectal cancer were taken as outcome measures. The only significant risk factor in the multivariate model for colectomy was transplantation itself, which increased the risk of colectomy due to intractable disease (Wald statistic; P = .001). None of the variables available for analysis were found to influence the risk of colon cancer significantly. Graphs showing the dependence of the instantaneous risk of cancer on the time from onset of IBD and its independence from the latter in the case of colectomy are presented. The use of a unique statistical methodology described for the first time in this setting led us to the somewhat surprising conclusion that transplantation and concomitant use of immunosup­ pression accelerate the progression ofIBD. At the same time, transplantation does not affect the incidence of colorectal cancer.
    [Show full text]
  • Colonoscopy Outcomes by Duration of NPO Status Prior to Colonoscopy
    NPO Status Prior to Colonoscopy Evidence-based Synthesis Program Table 1. Study Characteristics Patient Characteristics Study/Region/ Inclusion/Exclusion Criteria (expressed in means unless NPO status groups Risk of Bias Funding Source otherwise noted) Abdul-Baki Inclusion Criteria: ambulatory N=382 NPO status group 1a: Split-dose PEG-E with 2L For RCTs 200813 outpatient adults undergoing consumed evening before and 2L day of Sequence generation: elective colonoscopies Age (yr): 55 colonoscopy (to be completed 2 hours before adequate Location: Gender (Male %): ~61 the procedure) + tegaserod 6 mg pills (1 tablet Lebanon Exclusion Criteria: patients Race (%): NR night before and one 2.5 hours before Allocation concealment: <18 years of age, presence of BMI: NR procedure); (n=92) adequate Study design: severe renal impairment, NPO status group 1b: matched placebo (n=107) RCT (4-way) moderate or severe hepatic Co-existing conditions (%) Blinding: yes, impairment, a history of bowel Inflammatory bowel disease: 4 Patients allowed regular diet until 6 pm day endoscopist, participant Funding source: obstruction, known allergies before colonoscopy and water until procedure (tegaserod) Industry to PEG or tegaserod Indications for colonoscopy time (%) Incomplete outcome data: Screening: 25 NPO status group 2a: PEG-E consumed no Abdominal pain: 24 evening before colonoscopy + tegaserod 6 mg Changes in bowel habits: 15 pills (1 tablet night before and one 1.5 hours Selective outcome Rectal bleeding: 21 before procedure) (n=94) reporting: no Anemia:
    [Show full text]
  • University of Birmingham the Use of Faecal Microbiota Transplant As
    University of Birmingham The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: Mullish, Benjamin H.; Quraishi, Mohammed Nabil; Segal, Jonathan P.; McCune, Victoria L.; Baxter, Melissa; Marsden, Gemma L; Moore, David; Colville, Alaric; Bhala, Neeraj; Iqbal, Tariq H.; Settle, Christopher; Kontkowski, Graziella; Hart, Ailsa L.; Hawkey, Peter M.; Williams, Horace R. T.; Goldenberg, Simon D. DOI: 10.1016/j.jhin.2018.07.037 License: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) Document Version Peer reviewed version Citation for published version (Harvard): Mullish, BH, Quraishi, MN, Segal, JP, McCune, VL, Baxter, M, Marsden, GL, Moore, D, Colville, A, Bhala, N, Iqbal, TH, Settle, C, Kontkowski, G, Hart, AL, Hawkey, PM, Williams, HRT & Goldenberg, SD 2018, 'The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines', The Journal of hospital infection, vol. 100, no. Supplement 1, pp. S1-S31. https://doi.org/10.1016/j.jhin.2018.07.037 Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research.
    [Show full text]
  • Surgery for Crohn's Disease and Ulcerative Colitis
    Surgery for Crohn’s Disease and Ulcerative Colitis What’s Inside? About Crohn’s disease and 2 ulcerative colitis When is surgery necessary? 3 Reasons for elective surgery 3 Conditions that require 5 immediate surgery Your health care team 7 Common procedures for 8 ulcerative colitis Common procedures for 17 Crohn’s disease Making the decision to have surgery 21 Preparing for surgery 23 After surgery 24 Dietary recommendations 24 Tools and resources 27 Improving quality of life 28 About CCFA Inside back cover (Disclaimer: Surgery information is up to date at the time of printing. Due to rapid advances and new findings, there may be changes to this infor- mation over time. You should always check with your doctor to get the most current information. This information should not replace the recom- mendations and advice of your doctor.) Crohn’s disease and ulcerative colitis are lifelong illnesses. Treatment with medication is the first therapeutic option. Eventually, some people living with Crohn’s disease or ulcerative colitis may require surgery. This brochure re- views possible reasons that make surgery necessary, describes the various proce- dures, and helps you to learn what to expect. 1 About Crohn’s disease and ulcerative colitis Crohn’s disease and ulcerative colitis belong to the same disease category, inflamma- tory bowel diseases (IBD). IBD causes chronic inflammation in the gas- trointestinal (GI) tract. Chronic inflammation impairs the ability of the affected organs to function properly, leading to symptoms such as abdominal cramping, diarrhea, rectal bleeding, and fatigue. While both diseases share many of the same symptoms, there are some important differences.
    [Show full text]
  • Patient Positioning and Operating Room Setup
    WHE15 6/16/2005 2:18 PM Page 150 15.1. Colorectal Resections: Patient Positioning and Operating Room Setup Tonia M. Young-Fadok, M.D., M.S., F.A.C.S. A. Room Layout: General Consideration 1. Is the operating room large enough to accommodate the equipment necessary for a minimally invasive procedure? This is a basic consideration when a laparoscopic case is assigned to an operating room (OR) not usually used for laparoscopic procedures or when performing an advanced procedure for the first time. Compared to an open case, laparoscopic procedures require consid- erably more space to accommodate the towers, monitors, and other specialized equipment. 2. Positioning of the OR table. In most minimally invasive colorectal resections, a portion of the procedure is carried out extracorporeally. To ensure optimal visualization for this part of the case, it is important that the operating table be well positioned beneath the OR lights. The orientation of the operating table (obliquely, longitudinally, or transversely) in relation to the anesthesia equipment, the shape of the room, and the OR doors also needs to be carefully considered because of the large amount of equipment that must be arrayed about the OR table. A poor table position may impede the repositioning of TV moni- tors or other equipment or hamper the circulating nurse’s ability to move about the room. 3. Two basic body positions are utilized for colorectal resections, the supine position and the modified lithotomy position. The choice of body posi- tion affects the subsequent OR setup. Surgeon preference and the type of pro- cedure to be performed dictate the position choice.
    [Show full text]
  • Bowel Resection Surgery
    Bowel Resection Surgery (Open Method) What is a bowel resection? A bowel resection is surgery to remove a part of the large or small intestine. These parts are shown on this diagram. small intestine large intestine Why do I need a bowel resection? You need a bowel resection to relieve the symptoms caused by a disease or problem in your bowel. Talk with your surgeon about the cause of your bowel problem. turn over How do I prepare for a bowel resection? Your doctor may tell you to have only clear fluids 2 to 3 days before your surgery. Clear fluids include: water apple juice clear sodas or pop consomme soup jello, popsicles or freezies clear tea or coffee Do not drink milk or eat any solid foods during this time. Your doctor or nurse will tell you how to prepare your bowels. You may need a bowel preparation and antibiotics before surgery. The bowel preparation will make you have enough bowel movements to clean out your bowel before surgery. Taking the bowel preparation the correct way is very important to decrease the risk of infection after surgery. If you take medications regularly, ask your doctor if the time or amount of medication you take needs to be changed before surgery. What happens during bowel resection surgery? You will have a general anaesthetic. This means you are asleep during the operation. The doctor makes an incision in your abdomen and removes the part of your bowel that is causing problems. How will I feel after surgery? You may feel pain, discomfort and nausea.
    [Show full text]