Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000052730
Ethics application status
Approved
Date submitted
5/11/2021
Date registered
17/01/2022
Date last updated
9/01/2023
Date data sharing statement initially provided
17/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Faecal microbiota transplant to improve motor function in patients with advanced Parkinson’s disease: A pilot study
Scientific title
Faecal microbiota transplant to improve motor function in patients with advanced Parkinson’s disease: A pilot study
Secondary ID [1] 304252 0
None
Universal Trial Number (UTN)
U1111-1271-2608
Trial acronym
FMT in PD
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 321965 0
Condition category
Condition code
Neurological 319688 319688 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Double blind randomised placebo cross over trial of faecal microbiota transplantation (FMT)
The study is a comparison of an experimental treatment (FMT) against placebo
The placebo arm will cross-over to treatment arm (FMT) after two placebo treatments and an assessment period
To maintain blinding, the treatment arm (FMT) will receive two placebo infusions after active treatment and an assessment period.
The 1st and 2nd infusions (FMT or placebo) will occur 2 weeks apart.
Following a 4 week gap participants will then cross over. The 3rd and 4th infusions (FMT or placebo) will also occur 2 weeks apart. Assessments will then occur at 4 weeks, 3 months and 6 months.

Each participant will receive FMT from one single donor, which will remain the same for both treatment visits. A total of three donors will be used in the trial.
The FMT used will be TGA-approved BiomeBoost.
Each treatment/placebo is 100ml and will be infused via Peg-J tube at a rate of 400ml/hr. FMT/placebo will be administered a total of 100ml of FMT via two 50ml syringes and a pump will ensure the above rate. The infusions will take place in the outpatient department under the supervision of the investigating team (nursing and medical supervision and monitoring). No intervention is required at home following the infusion but participants will contact the investigating team should they experience adverse effects, prompting medical review.

Assessments will occur at each visit
Assessments will include motor and non-motor Parkinson's disease rating scales.

Intervention code [1] 320590 0
Treatment: Other
Comparator / control treatment
Placebo will consist of 100ml sterile water with 10% glycerol and brown food colouring to mimic appearance of FMT syringes.
Administration of placebo will follow all the same procedures as FMT administration
Control group
Placebo

Outcomes
Primary outcome [1] 327570 0
Safety and tolerability of faecal microbiota transplant.
Adverse events related to FMT appear to be uncommon, often mild and self-limiting;
-Abdominal discomfort
-Infection - rare cases of bacteraemia, PEJ site infection
-Gastrointestinal disturbance - nausea, diarrhoea

Adverse events related to PEJ-tube infusion/manipulation not specific to FMT
- PEJ site leakage
- PEJ site infection
- PEJ tube blockage potentially resulting in a delay in receiving Duodopa
At each infusion participants will be monitored - vital signs are monitored and also participants will be asked to report any of the above symptoms.
At each visit participants will be asked again regarding the above symptoms
While adverse events will be queried at each appointment and serious adverse events will be monitored and reported, there are specific risk parameters that will be monitored conscientiously during infusion:
• Jejunal tube blockage is a potential complication. The infusion team (PD nurses) will be alerted to a blocked tube by the alarming syringe driver. This can be managed by ceasing the infusion temporarily and flushing the jejunal tube with normal saline. This is a situation not infrequently encountered in LCIG infusions also, and our PD clinical nurse specialists are therefore very experienced at managing this potential complication.
• Abdomoinal pain – transient, mild, cramping abdominal discomfort has been described with FMT. The infusion rate may be slowed or ceased (see below) should a participant report this.
• Fever – transient pyrexia has also been reported following FMT and participants will be monitored for one hour post FMT/placebo infusion. Any further signs of infection will be sought by the medical team and acted upon.
• Diarrhoea – abdominal pain with associated diarrhoea may occur acutely if the FMT is cool. Care will therefore be taken to ensure the sample has been warmed adequately to room temperature as per the standard procedure below.
• Deterioration in Parkinson’s disease symptoms
o Acutely at infusion time off LCIG – an extra dose of LCIG / Duodopa will be administered pre-and post-infusion to avoid this. Infusion time is expected to not exceed 2 hours.
o We feel it is unlikely for PD symptoms to deteriorate significantly in the medium/longterm as a result of FMT/placebo infusions. However, the DMC will monitor Hauser diaries and other assessment scores for unexpected results. An participant may be withdrawn if deemed to be experiencing unexpected motor deterioration. The treating neurologist may also titrate their usual PD medication regimen.
• PEG-J site infection – this is uncommon in LCIG therapy patients and is typically treated with topical or oral antibiotics.
. An adverse event or suspected adverse reaction is considered "serious" if, in the view of the investigators, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such events include anaphylaxis and peritonitis from stoma dehiscence.
Timepoint [1] 327570 0
Safety and tolerability are assessed
1. during the infusions (ie. infusion 1, 2, 3 and 4)
2. at each visit prior to next infusion (ie 2 weeks post first infusion (FMT or placebo), at 4 weeks post infusion 2, at 2 weeks post infusion 3)
3. at 4 weeks post last infusion (post infusion 4)
4. at 4 months post last infusion
5. at 11 months post last infusion
Primary outcome [2] 327571 0
Absolute change in daily OFF time based on patient’s Hauser diaries

Individuals with Parkinson's disease often describe "Off" symptoms as stiffness, slowness and re-emergence of tremor. Other "off" symptoms may include cognitive fog, temperature dysregulation, freezing of gait, or anxiety.
Timepoint [2] 327571 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [1] 402717 0
change in gastrointestinal symptoms of Parkinson's disease, as measured by the gastrointestinal dysfunction scale for Parkinson's disease ( GIDS-PD)
Timepoint [1] 402717 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [2] 404145 0
Change in Non-motor symptoms in PD (New Non-motor symptoms scale for Parkinson's disease)
Timepoint [2] 404145 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [3] 404539 0
Change in participant motor state rated using serial UPDRS motor subs-scores
Timepoint [3] 404539 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [4] 404540 0
overall change in health status measured by the EQ-SD
Timepoint [4] 404540 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [5] 404541 0
change in overall quality of life as measured by the Schwab and England Activities of Daily living
Timepoint [5] 404541 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [6] 405058 0
Change in non-motor symptoms of anxiety and depression as measured by the Hospital Anxiety and Depression Scale
Timepoint [6] 405058 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [7] 405059 0
Change in participant motor state as assessed by unified dyskinesia rating scale
Timepoint [7] 405059 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [8] 405060 0
Change in overall quality of life as measured by the PDQ-8
Timepoint [8] 405060 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion
Secondary outcome [9] 405061 0
Change in gastrointestinal symptoms of Parkinson's disease as measured by the Patient Assessment Constipation – Symptoms (PAC-SYM) scale
Timepoint [9] 405061 0
1. at 4 weeks post infusion 2 (ie 2 weeks following 2nd treatment of either FMT or placebo)
2. at 4 weeks post last infusion (post infusion 4 - FMT or placebo)
3. at 4 months post last infusion
4. at 11 months post last infusion

Eligibility
Key inclusion criteria
Patients with a clinical diagnosis of idiopathic Parkinson disease at time of referral, who are currently receiving levodopa/carbidopa intestinal gel (LCIG) via percutaneous endoscopic jejunostomy tube (either 16 or 24 hours per day)
Patients with >/= 3 hours of OFF time (defined as anything other than best ON)
Cognitive capacity to provide their own consent, based on clinical judgement of investigator
stable LCIG infusion rate for past 4 weeks
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Any patient who declines to participate in the study.
• The patient has a clinical diagnosis of an atypical Parkinsonism at the time of referral.
• Any patient with a diagnosis of inflammatory bowel disease or Clostridium difficile infection
• Any patient who has been on LCIG for less than 4 months
• Any patient who has received antibiotics within 6 weeks from enrolment date
• Any patient who has consumed probiotics within 6 weeks from enrolment date. There are no other specific dietary restrictions during the study.
• Any patient who has required a change in LCIG infusion rate in the past 4 weeks
• Life-threatening food allergies, e.g. nut allergy.
• Pregnancy or lactation.
• Contraindication to preferred means of administration, e.g. oesophageal stricture limiting nasogastric tube insertion.
• Patients with decompensated cirrhosis, uncontrolled HIV (CD4 count < 240 cells/mm3), recent bone marrow transplant (within past 6 weeks), or other significant immunodeficiency.
• Patients taking major immunosuppressive agents, including high dose corticosteroids (e.g. prednisolone = 60 mg/day), calcineurin inhibitors, mTOR inhibitors, lymphocyte-depleting biologic agents, anti-TNF therapy, and recent use of chemotherapeutic anti-neoplastic agents (past 6 weeks).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will occur. Participants will be randomised using computer generated randomisation by the investigating team. The members of the team performing randomisation will be blinded to the patients and randomisation will occur based on participant study code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation will be used for randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Baseline characteristics data and trial phases data with continuous variables between groups will be compared using non-parametric Kruskal-Wallis test, with statistical significance set at p<0.05. Post-hoc testing will be performed with pairwise comparison using Kruskal-Wallis test if statistical significance is reached. Nominal variables between groups will be compared using Chi-Square test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2022
Actual
11/07/2022
Date of last participant enrolment
Anticipated
4/08/2023
Actual
Date of last data collection
Anticipated
5/08/2024
Actual
Sample size
Target
24
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21034 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 35874 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 308630 0
Hospital
Name [1] 308630 0
Training education and study leave funding, Westmead Hospital
Country [1] 308630 0
Australia
Primary sponsor type
Hospital
Name
Westmead Hospital
Address
Westmead Hospital
Cnr Darcy and Hawkesbury Rds,
Westmead
NSW 2145
Country
Australia
Secondary sponsor category [1] 311152 0
None
Name [1] 311152 0
Address [1] 311152 0
Country [1] 311152 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308557 0
Western Sydney Local Health District HREC
Ethics committee address [1] 308557 0
Ethics committee country [1] 308557 0
Australia
Date submitted for ethics approval [1] 308557 0
14/07/2021
Approval date [1] 308557 0
14/09/2021
Ethics approval number [1] 308557 0
2021/ETH00772

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111130 0
Prof Victor Fung
Address 111130 0
Movement Disorder Unit
Department of Neurology
Westmead Hospital
Corner of Darcy and Hawkesbury Rds,
Westmead
NSW 2145
Country 111130 0
Australia
Phone 111130 0
+61 2 88906753
Fax 111130 0
Email 111130 0
[email protected]
Contact person for public queries
Name 111131 0
Laura Williams
Address 111131 0
Movement Disorder Unit
Department of Neurology
Westmead Hospital
Corner of Darcy and Hawkesbury Rds,
Westmead
NSW 2145
Country 111131 0
Australia
Phone 111131 0
+61 2 88906753
Fax 111131 0
Email 111131 0
[email protected]
Contact person for scientific queries
Name 111132 0
Victor Fung
Address 111132 0
Movement Disorder Unit
Department of Neurology
Westmead Hospital
Corner of Darcy and Hawkesbury Rds,
Westmead
NSW 2145
Country 111132 0
Australia
Phone 111132 0
+61 2 8890 6834
Fax 111132 0
Email 111132 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Demographic data
Safety and adverse event data
Change in motor rating scales
Change in non-motor symptom scales
When will data be available (start and end dates)?
data available 3rd quarter 2023 after scientific publication
No end date
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
only to achieve the aims in the approved proposal
How or where can data be obtained?
access subject to approvals by Principal Investigator Professor Victor Fung [email protected]


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.