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Trial record 7 of 47 for:    Bowel Diseases | Recruiting Studies | fecal microbiota transplantation

Pilot Study of Fecal Transplantation Using a Unique Diet for Donor and Recipient in Mild to Moderate Treatment Refractory Colitis in Inflammatory Bowel Disease

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ClinicalTrials.gov Identifier: NCT02734589
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
Prof. Arie Levine, Wolfson Medical Center

Brief Summary:
Changing the microbiota has become the most intriguing target for intervention in inflammatory bowel disease (IBD). Dietary therapy is successful in mild to moderate Crohn's disease and may be effective in mild to moderate ulcerative colitis (UC) as well, though dietary interventions in UC are just getting underway. However these interventions are less likely to be effective for the more severely inflamed or refractory end of the spectrum. Fecal transplantation (FT) has been suggested as a method to treat refractory IBD, but most studies have been unsuccessful in establishing remission and especially prolonged remission. The investigators hypothesize that this is due to selection of random donors and the inability to maintain an optimal microbiota eco system post transplant. Diet is a powerful tool to modulate the microbiota. The investigators propose to modify FT using a novel protocol and approach that we have developed. We have developed a unique diet that is geared to rectify dysbiosis in UC and damage to the mucous layer in active UC. The investigators intend to condition both donor and recipient with the diet to achieve optimal conditions for transplant to succeed for both donor and recipient .The investigators intend to evaluate this protocol in adults with active UC that are refractory to medications. The investigators will start with a randomized controlled trial involving 76 transplanted patients, however in the first pilot stage The investigators will enroll 34 patients, and extend the study if there is a trend for better outcomes with the dietary conditioning protocol. Furthermore, The investigators hope to identify successful donors during this period to use during the study extension.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Other: Fecal transplantation Other: Unique novel Diet for UC and Unique novel Diet for the donor + FMT Other: Unique novel Diet for UC Not Applicable

Detailed Description:

The first exploratory phase will take place in 34 subjects aged 18-60, with refractory established UC, over 12 weeks. Study type- It will be an open label 3 arm multicenter randomized controlled single blinded study, with review of endoscopic activity by blinded reviewers. Patients will be randomized to one of three groups; Group 1 will undergo standard fecal transplantation by colonoscopy on day 1 and 60 ml rectal enemas on days 2 and 14 from the same donor without dietary conditioning, while Group 2 will undergo the same transplantation (colonoscopy and enemas at night day 2 and day 14), with dietary pre-conditioning of the donor for 14 days and dietary treatment of the recipient immediately after transplantation and for the following 12 weeks.We will attempt to use the same donors for group 1 and 2 by using the preconditioning stool for group 1 and the post conditioning stool for group 2 in order to control for the "donor effect". Group 3 will receive dietary therapy only. Should the first stage be successful, The investigators will continue the fecal transplantation trial to reach our target enrolment number ( 76 patients) for transplantation + 20 dietary controls. This second stage of the study will involve fecal transplantation in an additional 52 patients in order to have a total of 76 transplanted patients from the two phases.

since physicians will be able to distinguish between stool and colored saline during colonoscopy.

Subjects may continue their stable medications but should not start new medications during the 8 week period unless they fail to respond. Steroid weaning can commence from day 14.

Patients will be seen on weeks0, 2, 6, 8, 12 and during week 20. Week 6 will be only a dietitian visit. The last visit is a visit off diet to evaluate sustainability of the initial intervention, safety and changes in BMI due to FT or diet. A telephone conversation to assess SCCAI will be made at week 1 and week 7. At each visit (weeks 0, 2, 6, 8, 12, 20) patients will have Weight, a disease activity score, PGA, CBC, CRP, albumin and complete chemistry panel performed. Adverse events and medications used will be recorded at each visit.Stool samples for microbiome (16S rDNA, Short chain fatty acid analysis) and Calprotectin will be measured locally at baseline, weeks 2, 8 and 12. All patients (patients in group 1,2 and 3) will have a repeat sigmoidoscopy performed at week 8. A food frequency questionnaire will be performed on week 0 and a food diary will be collected at week 2 and 12. A compliance questionnaire will be completed on weeks 2, 8and 12. A 24 hours recall will be collected at weeks 0, 2 and 6.

Open Label treatment of refractory patients:

Patients in group 1 and 3 who do not improve by week 8 ( day 56) may be treated with the identical protocol used in Group 2 at the physicians discretion or receive any other therapy. These patients will be seen at day 14 and 56 as above, and have the same monitoring of dietary compliance by food diaries at days 14 and 56 and biological samples as above. Patients in group 1 or 2 in remission from FT, may receive up to 2 rescue enemas during the 8 weeks of the study from their original donor.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Fecal Transplantation Using a Novel Conditioning Method for Donor and Recipient in Mild to Moderate Treatment Refractory Colitis in Inflammatory Bowel Disease
Actual Study Start Date : January 24, 2017
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Fecal microbiota transplantation (FMT) without Diet
undergo standard fecal transplantation by colonoscopy on day 1 and 60 ml rectal enemas on days 2 and 14 from the same donor without dietary conditioning.
Other: Fecal transplantation
Transplantation of fecal bacteria from a healthy individual into a recipient- ulcerative colitis patient via colonoscopy and enemas
Other Name: Fecal microbiota transplantation (FMT)

Experimental: FMT with Diet for the donor and for the recipient
undergo standard fecal transplantation by colonoscopy on day 1 and 60 ml rectal enemas on days 2 and 14 with dietary pre-conditioning of the donor for 14 days and dietary treatment of the recipient immediately after transplantation and for the following 12 weeks.
Other: Unique novel Diet for UC and Unique novel Diet for the donor + FMT
A developed unique diet that is geared to induces remission and decreases inflammation in patients with active UC. Also a conditioning diet for healthy subjects to be used by the donor prior to transplantation- a developed unique diet for two weeks.
Other Name: Ulcerative Colitis Diet (UCD) and the conditioning diet

Active Comparator: Dietary therapy only
The patient will receive detailed instructions regarding the UC diet to be used over 12 weeks without FMT.
Other: Unique novel Diet for UC
A developed diet that is geared to induces remission and decreases inflammation in patients with active UC.
Other Name: Ulcerative Colitis Diet (UCD)




Primary Outcome Measures :
  1. Clinical remission determined by Simple Clinical Colitis Activity Index (SCCAI) score <5 at week 8 for group 1 and 2 [ Time Frame: Day 56 ]

Secondary Outcome Measures :
  1. Improvement in the Simple Clinical Colitis Activity Index (SCCAI) score for each of the groups [ Time Frame: Days 56 & 84 ]
  2. Endoscopic Mayo endoscopic score <2 (for patients performing sigmoidoscopy) [ Time Frame: Day 56 ]
  3. Calprotectin < 250 µg/g [ Time Frame: Day 56 ]
  4. The need for additional therapy [ Time Frame: Week 12 ]
    According to the physician discretion

  5. change in the microbiome compared to baseline. [ Time Frame: For donor- day 14 and for recipient day 56 ]
    According to analysis of fecal samples



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent
  2. Established diagnosis of UC, disease confined to the large intestine, involving the rectosigmoid for at least 3 months.
  3. Age: 18 - 70 years ( inclusive)
  4. Mild to Moderate active disease, SCCAI of ≥5 and <10 with endoscopic subscore≥2
  5. Refractory to mesalamine 6 weeks, or steroids > 14 days, or immunomodulator 12 weeks or biologics at least 12 weeks therapy.
  6. No use or stable use for 2 weeks of medical cannabis.

Inclusion criteria Comments:

1. Patients can enter the trial if they are on steroids if they have been treated for at least two weeks with 40 mg prednisone or an intravenous steroid such as methylprednisolone and still suffer from a mild to moderate active disease.

Exclusion Criteria:

  1. Start of a new biologic in the previous 12 weeks.
  2. Evidence for Clostridium difficile infection.
  3. Any proven current infection such as CMV, positive stool culture or parasite.
  4. Current Extra intestinal manifestation of UC such as active arthritis or primary sclerosing cholangitis (PSC).
  5. Immune deficiency (other than drug induced).
  6. Current use of a calcineurin inhibitor
  7. Pregnancy.
  8. Suspected toxic megacolon, guarding on palpation, or signs of peritoneal inflammation
  9. Patients with other IBD unrelated disease such as autoimmune disorders, renal failure, fever or current infection (UTI, strep throat, pneumonia, etc), prior or current neoplasia
  10. Fecal Transplantation in the last 6 months.
  11. Fever >38
  12. Participation in another clinical interventional trial
  13. An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
  14. Inability or reluctance to use an enema.
  15. Anticipation for antibiotic use within the study period (such as for elective surgery or dental treatment).
  16. Acute severe UC in the past 3 months.
  17. Presence of a pouch or pouchitis.
  18. Patients > 60 years old using chronic medications except for the treatment for colitis.

Exclusion criteria Comments:

  • Patients will be excluded from the analysis if during the study and after the initial fecal transplant they did not perform the enemas, used antibiotics prior to day 42. Patients who required additional therapy such as additional FMT, steroids biologics or immunomodulators during the first 8 weeks will be considered failures on an intention to treat basis.
  • Patients with mayo< 2 at the baseline colonoscopy may receive the FMT and continue the follow up according to the protocol as an open lable based on the randomization. Those patients will be excluded from the final analysis.

Special populations (e.g children, unable to sign an informed consent, those under a guardian) and pregnant women will also be excluded.

Donors:

Donors will sign an informed consent and will be screened and included only if they satisfy the rigorous screening criteria of the protocol of the Ministry of Health of Israel for stool donors for Clostridium difficile infection which includes a list of medical and behavioral conditions as well as transmissible pathogens that need to be screened by history, anthropometry, blood and stool tests (available as supplement).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734589


Contacts
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Contact: Arie Levine, MD 972-3-5028838 arie.levine.dr@gmail.com
Contact: Chen Sarbagili ibd.chen@gmail.com

Locations
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France
Saint-Antoine Hospital, Universite Pierre et Marie Curie Not yet recruiting
Paris, France, 75571
Contact: Harry Sokol, MD    +330149283162    harry.sokol@gmail.com   
Principal Investigator: Harry Sokol, MD         
Israel
Wolfson Medical Center Recruiting
Holon, Israel, 58100
Contact: Arie Levine, MD    972 35028838    arie.levine.dr@gmail.com   
Contact: Chen Sarbagili    972 35028838    ibd.chen@gmail.com   
Principal Investigator: Arie Levine, MD         
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel
Contact: Nitsan Maharshak, MD    972-36947305    nmaharshak@gmail.com   
Principal Investigator: Iris Dotan, MD         
Principal Investigator: Nitsan Maharshak, MD         
Italy
Humanitas Clinical and Research Center Not yet recruiting
Milan, Italy
Contact: Silivio Danese, MD, PhD       sdanese@hotmail.com   
Principal Investigator: Silivio Danese, MD, PhD         
Catholic University of the Secret Heart Not yet recruiting
Rome, Italy
Contact: Franco Scaldaferri, MD    +390630155923    francoscaldaferri@gmail.com   
Principal Investigator: Franco Scaldaferri, MD         
Sponsors and Collaborators
Wolfson Medical Center
Investigators
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Principal Investigator: Arie Levine, MD Wolfson Medical Center
Principal Investigator: Yona Avni, MD Wolfson Medical Center

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Responsible Party: Prof. Arie Levine, Director, Pediatric Gastroenterology and Nutrition unit., Wolfson Medical Center
ClinicalTrials.gov Identifier: NCT02734589     History of Changes
Other Study ID Numbers: 0772-15
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Arie Levine, Wolfson Medical Center:
Ulcerative Colitis
Nutrition
microbiome
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Inflammatory Bowel Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes