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Trial registered on ANZCTR


Registration number
ACTRN12616000746437p
Ethics application status
Submitted, not yet approved
Date submitted
23/05/2016
Date registered
7/06/2016
Date last updated
4/12/2019
Date data sharing statement initially provided
4/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of oral, capsulised, frozen faecal matter transplant for the treatment of clostridium difficile diarrhoea.
Scientific title
Efficacy of oral, capsulised, frozen faecal matter transplant for the treatment of relapsing clostridium difficile diarrhoea in adults.
Secondary ID [1] 289259 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clostridium difficile diarrhoea 298838 0
Condition category
Condition code
Infection 298897 298897 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with treatment refractory C. difficle diarrhoea will be offered capsulised faecal matter transplantation as treatment. The faecal matter will be from an unrelated donor and once capsulised, frozen until required in the clinic.
Donors are to be healthy volunteers, 18-50 years old, nil previous medical conditions, taking no medications, faeces and blood will be screened for known transmissible pathogens and pass the Australian Red Cross Blood Donor questionaire.
Patients will recieve 15 capsules on 2 consecutive days and be followed up for symptom resolution and adverse events for up to 6 months.
Each inoculum will be prepared from the faeces of a single donor and a full treatment of
30 capsules contain sieved, concentrated material derived from approximately 50g of faecal matter (ie approximately 1.66g per capsule).
Patients will be offered the capsules by the investigators in the clinic and instructed to take them orally. Adherence will be directly observed by the investigator at this time.
Intervention code [1] 294805 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298370 0
Resolution of diarrhoea symptoms.
Assessed by:
Questionnaires recording stool frequency and consistency (composite outcome).
Questionnaires have been designed specifically for this study
Timepoint [1] 298370 0
72 hours, 1 week and 6 months post commencement of faecal transplant therapy.
Primary outcome [2] 298427 0
Safety of FMT in clinical practice.
Possible adverse events will be reviewed by use of a modification of the Common Terminology Criteria for Adverse Events version 3.0.23
Known or possible adverse effects are:
Common:
Post treatment –
mild abdominal bloating and cramping, diarrhoea, mild dehydration. In most cases this resolves completely within 72 hours.
Rare:
Fatigue, malaise, nausea, headache, foul breath,
Very Rare:
Vomiting and potential for aspiration, Rash
The long term effect of manipulating the bowel bacteria of a person is not known. Antibiotics do also alter the bowel bacteria and also pose a similar level of unknown risk. Even with careful screening, transmission of infection is possible.
Timepoint [2] 298427 0
72 hours, 1 week and 6 months post commencement of faecal transplant therapy.
Secondary outcome [1] 323956 0
Overall health score:
Overall health score will be reported on a Likert Scale of 1 to 10, with 1 being the lowest and 10 being “best possible health for you.”
Timepoint [1] 323956 0
72 hours, 1 week and 6 months post commencement of faecal transplant therapy.
Secondary outcome [2] 324094 0
Gastrointestinal-specific health score. The score will be reported on a Likert Scale of 1 to 10, with 1 being the lowest and 10 being “best possible health for you.”
Timepoint [2] 324094 0
72 hours, 1 week and 6 months post commencement of faecal transplant therapy.
Secondary outcome [3] 324095 0
bowel movements per day:
Numerical number as self reported by patients study diary
Timepoint [3] 324095 0
72 hours, 1 week and 6 months post commencement of faecal transplant therapy.

Eligibility
Key inclusion criteria
Recipients:
Any patient aged >18 years with treatment refractory CDAD (at least 2 failed treatments or requiring long term suppressive treatment) who does not have any of the exclusion criteria
Donors:
healthy, non-pregnant adults aged 18-50 years, taking no medications
BMI of 18.5-25, no significant medical history (with the exception of resolved traumatic injury or routine surgery), pass the Australian Red Cross Blood Donor Questionnaire (see appendix), passes general physical examination, refrained from eating common allergens within 5 days of stool donation, otherwise not to alter their diet
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Recipients:
Known delayed gastric emptying disorder, or symptoms consistent with delayed gastric emptying. Pregnant mothers.
Donors:
Any past or current malignancy including GI malignancy or polyposis
Personal or family history of inflammatory bowel disease or unexplained GI illness
History of irritable bowel syndrome, excessive gas, bloating, lymphocytic colitis, idiopathic chronic constipation, chronic use of laxatives or chronic diarrhoea
Any chronic medications
Use of probiotics or any OTC aids for regulating digestion
Antibiotics within the preceding 6 months
Major immunosuppressive medications, e.g. calcineurin inhibitors, exogenous glucocorticoids, biologic agents, etc.
Systemic anti-neoplastic agents
Recent (last 5 days) ingestion of a potential allergen (e.g., nuts, shellfish, eggs, peanuts)
History of gastrointestinal surgery (e.g., gastric bypass)
Metabolic syndrome
Neurological, neurodevelopmental disorder e.g. Parkinson’s disease, autism, etc.
Systemic autoimmunity, e.g., multiple sclerosis, psoriasis, vasculitis, connective tissue disease, any rheumatologic or inflammatory condition
Atopic diseases, e.g. asthma and eczema, food allergies, eosinophilic disorders of the gastrointestinal tract
Chronic pain syndromes, e.g., chronic fatigue syndrome, fibromyalgia

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Continuous variables will be tested for normal distribution using the Kolmogorov-Smirnov test. Categorical variables will be compared between patients who achieved resolution of diarrhoea and those in whom the first treatment failed using the Chi-squared test or Fisher exact test and continuous variables using the Mann-Whitney test. In addition, a logistic regression model with mixed effects will be used to identify factors associated with diarrhoea resolution after 1 treatment while controlling for clustering within donors. Wilcoxon signed rank, Friedman, and McNemar tests will be used to compare variables before and after treatment. A linear mixed model will be used to assess for variables potentially related to the secondary outcomes (bowel movements per day, gastrointestinal health score, and overall health score) while controlling for clustering within donors. Bowel movements per day will be compared with normal using a 1-sample Wilcoxon signed rank test. The Fisher exact test will be used to compare rates of successful treatment with our previous study and an exact binomial test to compare with historically reported rates of successful treatment.
The sample size was calculated using the prior published rate of diarrhoea resolution of 30% with standard antimicrobial treatment among patients with more than 3 relapses of CDI. Assuming a rate of clinical resolution of diarrhoea of 90% among study participants, we estimated the target sample size at 19 patients (2-tailed a = .05; 1 - beta = .90).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/07/2016
Actual
Date of last participant enrolment
Anticipated
1/07/2019
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
19
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 5823 0
Gold Coast Hospital - Southport
Recruitment hospital [2] 5824 0
Robina Hospital - Robina
Recruitment postcode(s) [1] 13274 0
4215 - Southport
Recruitment postcode(s) [2] 13275 0
4226 - Robina

Funding & Sponsors
Funding source category [1] 293637 0
Self funded/Unfunded
Name [1] 293637 0
Self funded by Researcher - Mr Jack Cross
Country [1] 293637 0
Australia
Primary sponsor type
Individual
Name
Researchers as sponsor: Mr Jack Cross
Address
Gold Coast University Hospital
1 Hospital Blvd
Southport QLD 4215
Country
Australia
Secondary sponsor category [1] 292471 0
None
Name [1] 292471 0
none
Address [1] 292471 0
none
Country [1] 292471 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 295073 0
Gold Coast Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 295073 0
PED Building
Gold Coast University Hospital
1 Hospital Blvd
Southport, QLD 4215
Ethics committee country [1] 295073 0
Australia
Date submitted for ethics approval [1] 295073 0
19/05/2016
Approval date [1] 295073 0
Ethics approval number [1] 295073 0
HREC/16/QGC/170

Summary
Brief summary
The majority of reported FMT procedures have been performed with fresh stool suspensions from related donors. This approach has practical barriers that hinder the development of scientifically sound treatment protocols. The use of fresh donations requires prior identification and screening of a suitable donor, thus precluding the use of FMT in acute situations. Furthermore, the limited viability of fresh samples, usually estimated at up to 6 hours, makes thorough screening of donors and donation aliquots impractical. To address these issues Yongster and colleagues have studied the use of a pre-prepared, frozen inoculum from unrelated donors delivered by both endoscopic and capsulized routes, however both of these studies have been pilot studies.
The capsulized form of FMT when compared to FMT delivered by endoscopic means this method may have positive effects on: The timing of the procedure due to reduced logistical issues, the safety of the procedure (reduced risk of endoscopic/anaesthesia complications) and a reduction of overall cost to the health budget
Strengthening the evidence base and clinical experience behind frozen, oral FMT will be of benefit to patients, staff and health services.
Patients will be offered oral FMT using pre-made frozen capsules with the FM souced from unrelated donors
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66018 0
Mr Jack Cross
Address 66018 0
Dept of Immunology and Infectious Diseases
Gold Coast University Hospital
1 Hospital Blvd
Southport QLD 4215
Country 66018 0
Australia
Phone 66018 0
+61 7 5687 0556
Fax 66018 0
+61 7 5687 0298
Email 66018 0
jack.cross@health.qld.gov.au
Contact person for public queries
Name 66019 0
Jack Cross
Address 66019 0
Dept of Immunology and Infectious Diseases
Gold Coast university Hospital
1 Hospital Blvd
Southport QLD 4215
Country 66019 0
Australia
Phone 66019 0
+61 7 5687 0556
Fax 66019 0
Email 66019 0
jack.cross@health.qld.gov.au
Contact person for scientific queries
Name 66020 0
John Gerrard
Address 66020 0
Dept of Immunology and Infectious Diseases
Gold Coast University Hospital
1 Hospital Blvd
Southport QLD 4215
Country 66020 0
Australia
Phone 66020 0
+61 7 5687 0000
Fax 66020 0
Email 66020 0
john.gerrard@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.