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Development of a Novel Treatment for Clostridium Difficile

Periodic Report Summary 1 - DNTCD (Development of a Novel Treatment for Clostridium Difficile)

Project Context and Objectives:
The main aim of this project (DNTCD) is to exploit the need for effective treatment of Clostridium difficile (c.diff) and the restoration of the patient‘s iatrogenically degraded gastrointestinal flora, to immunise them against further infection.
Clostridium difficile is a Gram-positive spore-forming toxigenic bacterium that is controlled by the normal flora in the human intestine (1, 2). (The bacterium is also present in farm, companion and zoo animals (3)). It is now a leading cause of healthcare associated infection causing diarrhoea and colitis (ulceration and bleeding from the colon), typically after the use of broad-spectrum antibiotics. Diarrhoea is a nearly constant adverse effect of irradiation of the pelvis and is a factor in immunosuppressive therapy, including cytotoxics and proton pump inhibitors. The clinical presentation ranges from self-limited diarrhoea to severe life-threatening pseudomembranous colitis and toxic megacolon. The incidence of this disease is increasing, resulting in major medical and economic consequences (4). Although most cases respond quickly to medical treatment, C.difficile colitis may be serious, especially if diagnosis and treatment are delayed. Recurrent disease represents a particularly challenging problem.

• We wish to exploit the need for effective treatment for nosocomial diarrhoea especially that caused by Clostridium difficile disease (CDD). Patients treated with broad spectrum antibiotics are at greatest risk of CDD diarrhoea and many of those affected are hospitalised elderly patients with serious underlying illnesses.
• Antibiotics can cause disruption of the normal intestinal flora, an important part of the immune system, leading to an overgrowth of CDD. Currently, some 2350 patients suffering from chronic CDD in a number of countries have been treated by faecal bacteriotherapy (FB), using samples collected from donors.

• Although this procedure is reported, in a number of small studies, to be around 90% effective, it is hazardous, in that infection from the donor could be transmitted to the patient and it involves delivery of faecal samples into the duodenum via a nasal probe.

• We propose to treat CDD using a modified FB to restore the patient’s original intestinal flora (employing samples collected from the patients themselves prior to their treatment)

• We will produce novel enteric-coated capsules, containing processed freeze dried colonic flora that can be swallowed by a patient to restore their intestinal flora and immunise them against further infection by CDD. RFID tags will be employed to associate capsules with the relevant patient and assist with sample inventory.

• The outcome will be a non-antibiotic medicament to treat and prevent CDD The consortium plan to patent the IPR from the project, exploit and disseminate the technology.
Project Results:
The first period of the DNTCD project was dominated by the need to design the collection/processing containers for the faecal matter, order the moulds and produce 100 sets for trial purposes, and also to design and manufacture the RFID technology to enable tracking of samples through the healthcare environment. The project website would be designed and made live, and preliminary tasks in other work packages would commence. More detail on planned tasks in the first reporting period are given below.

The project was divided into 9 work packages, with WP8 being exploitation and dissemination & WP9 project management, both of which would run throughout the project duration.

WP1 was planned in three tasks to be completed by the end of the period- design of the containers, ordering of moulds, and manufacture of 100 containers for evaluation.
WP2 involved the design of a suitable RFID tracking system, along with trials in a hospital environment, followed by a report on the trial with further modifications if required.
WP4 required the ethics approval for the hamster trials, and the first phase of the trials would be performed (in-vivo analysis against non-toxic strains)
WP5 activities expected the ethics approval from relevant authorities for the involvement of humans in the collection and processing trial, identification of healthy volunteers and hospital patients for the trials, and the commencement of collection of faecal matter for processing in WP3
WP6 activities involved the creation of the public project website and also commencement of the development of the database to record and track samples through the healthcare environment.
WP7 was concerned with assessment and evaluation

Potential Impact:
Due to the initiating SME, Willana, withdrawing from the project and as a consequence of the extensive efforts invested in trying to identify a replacement partner to fill their role, it was discovered that alternative and effective pharmaceutical treatments for c.diff have and continued to be developed. These traditional treatments are more cost effective, space effective and less psychologically challenging than the remedy for c.diff proposed under the project. Therefore even of the project had continued their would likely have been no discernible positive impact from the project outcomes, this being the primary reason for the decision to terminate the project.

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