The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000375156
Ethics application status
Approved
Date submitted
5/03/2019
Date registered
11/03/2019
Date last updated
6/12/2019
Date data sharing statement initially provided
11/03/2019
Date results information initially provided
11/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised, controlled phase 1 study to investigate the safety and efficacy of orally administered squalamine in subjects with Motor Neuron Disease
Scientific title
A randomised, controlled phase 1 study to investigate the safety and efficacy of orally administered squalamine in subjects with Motor Neuron Disease
Secondary ID [1] 297560 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease 311792 0
Condition category
Condition code
Neurological 310410 310410 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to Group A will receive standard care and Squalamax over a period of 12 months.
Participants randomised to Group B will receive standard care only for the first three months. After this period, Group B participants will receive standard care and will also be treated with Squalamax for 9 months.

Each dose of Squalamax contains 1.95g Shark Liver ComplexTM, which consists of dogfish shark liver powder containing natural shark liver oil (117mg), Squalene (1.37mg) and Squalamine (390µg). Squalamax will be administered orally in capsule form at the highest dose recommended by NuGen Nutrition Inc. Supplement Facts “Directions: Take 3 capsules 1-3 times per day or as directed by your healthcare professional”. Three capsules will be self-administered by the participant 3 times per day for a total of 9 capsules. The total daily dose of squalamine per day is 1.2 mg. Participants will be asked to complete a daily medication record to allow evaluation of compliance.
Intervention code [1] 313794 0
Treatment: Other
Comparator / control treatment
The comparator group will be participants randomised to Group B. These participants will receive standard care for the first three months of the trial. Standard care refers to the treatment the participant's physician would ordinarily prescribe for them according to their symptoms.
Control group
Active

Outcomes
Primary outcome [1] 319280 0
New adverse events (AEs), e.g. diarrhea and the status of existing AEs to assess safety. The Investigator may elicit symptoms using an open-ended question, followed by appropriate questions that clarify the patient’s verbatim description of AEs or change in concomitant medications.
Timepoint [1] 319280 0
Adverse events will be assessed every month for 12 months after commencement.
Primary outcome [2] 319281 0
Physical examination will be conducted to assess safety and will include assessments of the participant’s general appearance, skin and lymphatics, EENT, cardiovascular system, respiratory system, abdomen/gastrointestinal system, and musculoskeletal system.
Timepoint [2] 319281 0
Physical examination will be assessed at screening, 3 months, 6 months, 9 months and 12 months after commencement.
Secondary outcome [1] 367551 0
Changes in gut-derived toxins in plasma. Blood samples (60ml) will be collected from participants and mass spectrometry analysis will be used to measure plasma levels of toxins,
Timepoint [1] 367551 0
Blood samples will be collected from participants at entry into the trial (at baseline) and after 3 months and 12 months after commencement.
Secondary outcome [2] 367608 0
Progression of disability using the ALS Functional Rating Scale (ALS FRS-R).
Timepoint [2] 367608 0
The Revised ALS Functional Rating Scale (ALS FRS-R) will be measured at baseline and every month for the first three months of the study followed by quarterly during the 9 month extension period (i.e. at 6, 9 and 12 month visits following commencement).
Secondary outcome [3] 367610 0
Respiratory function using respiratory function testing (RFT) will be performed according to the American Thoracic Society/European Respiratory Society Guidelines.
Timepoint [3] 367610 0
Respiratory function will be measured at baseline, at 3 months, 6 months, 9 months and 12 months following commencement.
Secondary outcome [4] 367611 0
Body Mass Index (BMI) will be calculated using the subject’s weight (in kilograms) divided by the participant’s height squared (in centimetres). Weight will be measured using a digital scale. Height of participants (without shoes) will be measured using a tape measure affixed to a wall.
Timepoint [4] 367611 0
Body weight will be measured in kilograms at baseline and every 3 months throughout the duration of the study. More frequent weight may be obtained at the discretion of the investigator. Standing height will be measured in all patients at baseline. If possible, height will be measured in the morning of the study visit day.

Secondary outcome [5] 367614 0
Changes in gut microbe levels in faecal samples using DNA sequencing of the faecal microbes.
Timepoint [5] 367614 0
Faecal samples will be collected from participants at entry into the trial (at baseline), after 3 months and 12 months of treatment for study at a later date.

Eligibility
Key inclusion criteria
- Clinically definite or clinically probable MND defined according to the revised El Escorial criteria
- Age >18 years
- Provision of informed consent from the patient
- Willingness to give written informed consent and willingness to comply with the study
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inability of patient to provide consent
- Inability to swallow capsules
- Participation in another/other clinical trials
- Prohibited concomitant medications: antibiotics, probiotics

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by Stata 15
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The hypothesis of this study is that Squalamine targets bacteria that produce toxins known to be neurotoxic and that by eliminating these bacteria, the effects of these toxins within the body decreases thus slowing disease progression. This is a phase 1 study designed to obtain information on the tolerability of Squalamine in MND patients and the effects of this drug on gut microbes and their derived toxins. A randomisation schedule for n=30 patients will be developed by the study statistician with equal allocation to the control and treatment groups. Statistical analysis will occur at completion of the trial in the form of descriptive statistics. Tolerability and safety will be assessed by the presence of adverse events and decline in physical health, both of which are assessed regularly during the study period. The comparison of interest for toxin levels is between the control and treatment group for the change between baseline and 3 months and baseline and 12 months.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 25856 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 302112 0
Charities/Societies/Foundations
Name [1] 302112 0
Wesley Medical Research
Address [1] 302112 0
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive, Auchneflower, Queensland, 4066
Country [1] 302112 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Wesley Medical Research
Address
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive, Auchneflower, Queensland, 4066
Country
Australia
Secondary sponsor category [1] 301944 0
None
Name [1] 301944 0
Address [1] 301944 0
Country [1] 301944 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302791 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [1] 302791 0
The Wesley Hospital
PO Box 499
Auchenflower, Queensland 4066
Ethics committee country [1] 302791 0
Australia
Date submitted for ethics approval [1] 302791 0
22/08/2017
Approval date [1] 302791 0
21/11/2017
Ethics approval number [1] 302791 0
1741

Summary
Brief summary
Motor Neuron Disease (MND) is a fatal neurodegenerative disease. MND is thought to arise from a combination of genetic susceptibility and environmental exposure, possibly due to a multi-stage process. There is considerable evidence that gut health is important in human disease and particularly in neurodegenerative disease. Given the lack of proven therapies in MND, there is an urgent need for new approaches. A range of approaches have been suggested and could involve diet, probiotics, prebiotics or antibiotics or therapies to antagonize the effects of the toxic molecules.

This trial will study the effects of squalamine, an antibacterial first discovered in the dogfish shark that has a novel mode of action, and its efficacy as treatment aimed at improving gut health in MND patients. Squalamine is effective against methanobacter, which are difficult to detect, but are the likely organism responsible for methylation by gut microbes. Squalamine is rare, being one of the few non-toxic antibacterials which is active against this class of gut microbes. Squalamine is an attractive candidate because it is already widely available as a natural product in the dietary supplement Squalamax.

This study will assess the safety and efficacy of squalamine (at a daily dose of 1.2 mg) in the dietary supplement Squalamax in patients with MND.

The study includes 2 main periods: an unblinded treatment period (3 months) and an open label long term follow up phase (9 months). Patients in the standard care arm (i.e. no drug) will be switched to Squalamax treatment after 3 months.

This study will test:
- the tolerability of squalamine in patients with MND (indicated by diarrhoea or other symptoms).
- the effects of squalamine on levels of gut derived toxins (before and after treatment with squalamine)
- the effects of squalamine on levels of gut microbes in MND patients (collection of faecal samples for later analysis)
- the effects of squalamine on MND standardised assessments (Amyotrophic Lateral Sclerosis Revised Functional Rating Scale (ALS-FRS R), Respiratory function testing (RFT)) and comparing treated and untreated patients over 3 months.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91418 0
Prof Pamela McCombe
Address 91418 0
UQCCR
Building 71/918
Royal Brisbane Women’s Hospital
Herston QLD 4029
Country 91418 0
Australia
Phone 91418 0
+61 7 33466017
Fax 91418 0
Email 91418 0
pamela.mccombe@uq.edu.au
Contact person for public queries
Name 91419 0
Dr Kelley Foster
Address 91419 0
Wesley Medical Research
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive
Auchenflower, Queensland, 4066
Country 91419 0
Australia
Phone 91419 0
+61 7 37211503
Fax 91419 0
Email 91419 0
kfoster@wesleyresearch.com.au
Contact person for scientific queries
Name 91420 0
Prof Pamela McCombe
Address 91420 0
UQCCR
Building 71/918
Royal Brisbane Women’s Hospital
Herston QLD 4029
Country 91420 0
Australia
Phone 91420 0
+61 7 33466017
Fax 91420 0
Email 91420 0
pamela.mccombe@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary