Dr Samuel is currently recruiting patients for the following clinical trials. Please contact him via this website or his Crohn’s and colitis clinic  Tel: 9722 8794 Fax: 9722 7752.

by Andrea Levy

1. Faecal Microbiota Transplantation in Ulcerative Colitis (FOCUS)

http://clinicaltrials.gov/ct2/show/NCT01896635

The FOCUS Study is the exciting new Australian study of “Faecal Microbiota Transplantation” (FMT) for patients with active mild to moderate ulcerative colitis (despite medications). It is a placebo controlled study, consisting of one colonoscopy treatment followed by patient-administered enemas. Patients who fail to improve can get open-label FMT after they conclude their study period. The FOCUS Study will run only till the end of this year

Contact: Dr Samuel, our study coordinator Sudarshan Paramsothy on focusstudygroup@gmail.com or my Crohn’s and colitis clinic.

The FOCUS Team: Michael Kamm, Hazel Michell, Thomas Borody, Alissa Walsh, Johan van den Bogaerde, Doug Samuel, Susan Connor, Watson Ng, Rupert Leong, Enmoore Lin, Sarah Finlayson and Sudarshan Paramsothy

Please contact one of our team for access to password protected information sheets:

FOCUS Participation Information and Consent Form FOCUS Enema Storage, Administration and Faecal Sample Collection Sheet

Invitation

You are invited to participate in a research study into the efficacy and safety of regular “healthy donor” faecal microbiota administration as a treatment for chronic active ulcerative colitis.

“Efficacy” refers to the effectiveness of a therapy or the ability of a therapy to
successfully produce the desired result – in this case, reducing the severity of
ulcerative colitis and associated symptoms.

The study is being conducted by Dr Douglas Samuel, Gastroenterologist at Bankstown-Lidcombe Hospital. The study is part of a national collaborative study coordinated by Australian researchers into ulcerative colitis. Other sites include St Vincent’s Hospital, Darlinghurst with Dr Alissa Walsh.

Before you decide whether or not you wish to participate in this study, it is important for you to understand why the research is being done and what it will
involve. Please take time to read the information carefully, and if you wish, discuss
it with your family, friends and your GP. The study doctor will be happy to discuss
it with you and explain any words or information you do not fully understand. Ask
questions if anything is unclear or if you would like more information. Take time to
decide whether or not you wish to take part.

What is the purpose of this study and what is Faecal Microbiota Transplantation (FMT)?

The purpose of this study is to investigate whether faecal microbiota transplantation (FMT), a therapy comprised of a faeces mixture provided by healthy human donors is an effective and safe treatment for chronic active ulcerative colitis (UC) unresponsive to standard medical therapy.

Ulcerative colitis is a chronic bowel condition characterised by inflammation of the large intestine and rectum. Associated symptoms typically include, diarrhoea, rectal bleeding, urgency to defecate and incontinence.
While the exact cause of UC is unknown, there is now compelling evidence that the gut bacteria play a central role in the development of UC, by stimulating an inappropriate immune system response. Current standard treatment for ulcerative colitis involves medications that alter the immune system response, but these only work in a proportion of patients with UC and can have associated side effects.

This in turn has directed research efforts into alternative therapies that look at restoration or replacement of a patient’s gut bacteria with gut bacteria obtained from a healthy donor with the aim of correcting any abnormalities and restoring missing components. The human bowel contains a complex population of gut bacteria. These gut bacteria and the chemicals they produce affect the body and these effects can have both positive and negative impacts on a person’s health. The normal or natural human gut bacteria protect us from pathogenic or “bad” bacteria.

Faecal microbiota transplantation (FMT) involves the infusion of healthy human  donor faeces via colonoscope or enema into the “sick” diseased bowel of the patient. The use of healthy human gut bacteria in the faeces appears to be the most “complete probiotic” treatment possible, capable of eradicating “bad bacteria” and supplying “good” bacteria for re-colonisation and restitution of normal gut bacteria.

There has been recent evidence published in the medical literature demonstrating  the effectiveness of FMT in treating Clostridium difficile infection (CDI), a gastrointestinal infection caused by a bacteria, that can often be unresponsive to multiple courses of antibiotic therapy. Given that FMT is capable of successfully treating unresponsive CDI colitis, FMT may have a role in other diseases where bacteria play a role in disease development, such as UC. Restoration of healthy gut bacteria may represent an effective therapy for UC.

There have been a few individual patient reports and a small series of reports suggesting possible benefit of FMT for UC, but as of yet there have been no published clinical trials to confirm this. We are conducting a trial to determine the benefit and safety of regular FMT therapy in UC. We also aim to collect and analyse faecal samples from healthy donor mixtures along with study patients to investigate changes in the gut bacteria of UC patients undergoing FMT that may be associated with benefit.

Why have I been invited to participate in this study?

You are eligible to participate in this study because you have chronic active mild or moderate Ulcerative Colitis of >3 months duration currently not in remission and satisfy the selection criteria for study participation.

What if I don’t want to take part in this study, or if I want to withdraw later?

Participation in this study is voluntary. It is completely up to you whether or not you participate. If you decide not to participate, it will not affect the treatment you receive now or in the future. Whatever your decision, it will not affect your relationship with the staff caring for you.

New information about the treatment being studied may become available during the course of the study. You will be kept informed of any significant new findings that may affect your willingness to continue in the study.

If you wish to withdraw from the study once it has started, you can do so at any time without having to give a reason. There are no consequences that will arise from withdrawing from the trial.

Participation is entirely free and voluntary and patients are free to withdraw at any stage for any reason. Study withdrawal will not influence your relationship with the study investigators or the quality of care that you will receive. Patients will be able to access and complete the remainder of a total of 8 weeks of active FMT study enema therapy in an open label manner post study withdrawal if they so wish.

However, it may not be possible to return your samples to you or withdraw your data from the study results if these have already had your identifying details removed.

What does this study involve?

If you agree to participate in this study, you will be asked to sign the Participant
Consent Form.

Individual patient participation duration will consist of 8 weeks of study therapy and then follow up in a further 8 weeks time.
The treatment being investigated in this study differs from the standard treatment offered in this institution because of its use of faecal microbiota transplantation(FMT) with healthy donor. FMT is attracting increasing global interest as an agent that may be useful in treating ulcerative colitis by restoring normal healthy gut bacteria, abnormality of which is believed to contribute to the disease.

This trial is a randomised, double blind, placebo controlled study comparing active
donor FMT therapy with placebo therapy

‘Randomised trial’: Sometimes doctors don’t know the best way of treating patients with a particular condition so comparisons need to be made between different treatments. To do this, study participants are put into groups and given different treatments, and the results are compared to see whether one treatment is better. To ensure the groups are similar to start with, a computer allocates each study participant into a group randomly, like the flip of a coin. Neither the doctor nor the study participant can decide which treatment the participant receives.

‘Blind trial’: In a “blind trial” the study participants do not know which treatment group they are in. If the trial is “double blind”, neither the doctor nor the study participant knows which treatment the participant is receiving (although, if the doctor needs to find out, he/she can do so).

‘Placebo’: A placebo is a dummy treatment that looks like the genuine medicine but contains no active ingredient.

If you agree to participate in this trial, you will be asked to undergo a medical review with medical history and physical examination to ensure you satisfy the study selection criteria. You will then be invited to participate in the study after thorough explanation of the study requirements, answering of any questions or concerns by a study investigator and completion of the accompanying informed consent sheet.

Recruited participants will undergo baseline blood and faecal tests as part of screening and assessment of disease activity. They will then be randomly allocated to either active FMT therapy or placebo for 8 weeks. Study subjects will be blinded i.e. they will not know which treatment arm they are randomly allocated to, as will be the study investigators.

Please contact us if you want more details of the 8 week study therapy. Individuals randomised to placebo therapy who are not in remission after the 8 week study period will be eligible to receive 8 weeks of open label (“unblinded”) active FMT therapy. 8 weeks post completion of final study therapy (whether blinded or open label /unblinded), study subjects will be reviewed for a final time for follow up on their clinical progress, assessment of disease activity and collection of final blood and faecal samples for study analysis.

Regular scheduled study monitoring calls and face to face visits will occur on an alternating weekly basis to assess patient response/disease activity, compliance and any side effects or other complaints. At predetermined time points on a monthly to second monthly basis, further faecal and blood samples will be collected for monitoring of disease activity and microbial analysis.

Participating in the trial will require some restrictions on your lifestyle during the study.
Recruited patients will be instructed to minimise alcohol intake to ≤ 2 standard drinks/day whilst they are participating in the study.

 While no specific dietary restrictions will be imposed, recruited patients will be advised to be judicious in the choice of food consumed during the study period to minimise the risk of food poisoning. Subjects are asked to exercise reasonable caution to avoid food poisoning during the study period, such as refraining from eating seafood or raw/uncooked food such as sushi, takeaway etc.

 Overseas or interstate travel will also need to be restricted during the study period to ensure compliance with study enema therapy 5 days per week.

 Recruited patients are precluded from any antibiotic or probiotic therapy during the study period or in the preceding 1 month and 3 months respectively.

In addition, the researchers may request access to your medical records to obtain information regarding your medical background and ulcerative colitis disease course (including prior medications / therapies) relevant to the study.

Are there risks to me in taking part in this study?

All medical procedures involve some risk of injury. In addition, there may be risks associated with this study that are presently unknown or unforeseeable. In spite of all reasonable precautions, you might develop medical complications from participating in this study.

There is minimal data to date with regards to FMT therapy for ulcerative colitis. Most published literature related to FMT therapy involves treatment of Clostridium difficile colitis, a gut infection. Such studies involving FMT administration to date have not demonstrated any serious adverse events. The known side effect profile and complications associated with FMT therapy is minimal.
A minority of patients (approximately 1 in 3 to 4 people) note some irregularity of bowel movements and excessive flatulence / bloating during the first couple of infusions but these symptoms are minor and usually resolve. Nonspecific abdominal discomfort has also been reported which again is usually minor and self-limiting.
There is a theoretical risk of infectious disease transmission from the donor (including but not limited to hepatitis, HIV, other viruses and parasites) associated with FMT. Donors of the stool used to constitute the FMT will be rigorously screened as per internationally published and accepted guidelines to minimise potential transmission of infectious disease. To date there have been no published cases or documented reports regarding transmission of infective agents / diseases by FMT in the medical literature. There is also a small risk of rupture / perforation of the rectum or bowel at the time of endoscopy (roughly 1 in 1000 cases), that may necessitate surgery.

Theoretically there is an extremely low likelihood this may also occur with enema self administration as the enema tip is inserted into the rectum.

Study participation will require the administration of either active donor FMT or placebo thoughout the study period which can be associated with the inconvenience of poor retention, urgency and incontinence, usually limited to the first couple of infusions. This may necessitate the use of incontinence pads. Repeated administration can also occasionally be associated with small tears or “micro-fissures” around the anus.
It is important that women participating in this study are not pregnant and do not become pregnant during the study as the effect of the study therapy of donor FMT on an unborn baby is unknown. If you are a woman of childbearing age and there is any possibility that you are pregnant, the researchers will need to perform a urine pregnancy test before you start in the study. Women of childbearing age will have to practice an effective form of contraception during the study.

Will I benefit from the study?

This study aims to further medical knowledge and may improve future treatment of ulcerative colitis, however it may not directly benefit you.

All study patients will have access to active study therapy with donor faecal enemas (either blinded or open label post blinded study therapy). This will ensure all study participants will have the capacity to benefit from trial participation if any study therapy efficacy is demonstrated.

Will taking part in this study cost me anything, and will I be paid?

Participation in this study will not cost you anything. This study is an investigator initiated project dependent on limited grant funding to cover the costs of the trial. The study investigators / doctors are not paid and provide their time and services for free. The study participants will be provided with the study treatment and care for free. Study participants will not be paid for participating in the trial.

What should I do if I want to discuss this study further before I decide?

When you have read this information, the researcher Dr Douglas Samuel and/or Dr Sudarshan Paramsothy will discuss it with you and answer any queries you may have. If you would like to know more at any stage, please do not hesitate to contact him/her on (02) 9722 8794.

2.AMG 181 Phase 2 Study in Subjects With Moderate to Severe Ulcerative Colitis

http://clinicaltrials.gov/show/NCT01694485

AMG 181 is a human anti-α4 β7 antibody given by subcutaneous injection. This randomized, double blind, placebo controlled study is looking to help patients with moderate to severe ulcerative colitis. AMG 181 targets the α4 β7 integrin heterodimer, blocking its interaction with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the principal ligand that mediates α4 β7 T cell gut-homing. At the end of the double blind period,  all subjects will be eligible to receive open label AMG 181.

3. A Study of Safety and Effectiveness of JNJ-54781532 in Patients With Moderately to Severely Active Ulcerative Colitis

http://www.clinicaltrials.gov/show/NCT01959282

JNJ-54781532 is an oral JAK 1/3 inhibitor. Tofacinib, an alternative JAK 1/3 inhibitor, is approved for use in rheumatoid arthritis and results of phase III studies in ulcerative colitis are pending. This randomized, double-blind, placebo-controlled, parallel group, dose-response study evaluates several doses of JNJ-54781532 in patients with moderately to severely active ulcerative colitis (UC). The JAK-STAT pathway is an essential part of the human gut’s immune system.  

4. A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Patients With Moderate to Severe Ulcerative Colitis in Patients Naive to TNF Inhibitors

http://clinicaltrials.gov/show/NCT02163759

This Phase III, double blind, placebo and active comparator controlled, multicenter study will investigate the efficacy and safety of etrolizumab in induction of remission in patients with moderately to severely active ulcerative colitis (UC) who are naïve to TNF inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment.

5. A Study of the Efficacy and Safety of Etrolizumab in Ulcerative Colitis Patients Who Are Refractory to or Intolerant of TNF Inhibitors.

http://clinicaltrials.gov/ct2/show/NCT02100696

For a more thorough search of clinical trials in Australia and around the world, visit the website www.clinicaltrials.gov. Additional portals to look for trials can also be found at the Australian Clinical TrialsWorld Health Organization and the IFPMA sites.