Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
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
Download to PDF
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
Query!
Scientific title
A randomised, controlled phase 1 study to investigate the safety and efficacy of orally administered squalamine in subjects with Motor Neuron Disease
Query!
Secondary ID [1]
297560
0
None
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease
311792
0
Query!
Condition category
Condition code
Neurological
310410
310410
0
0
Query!
Neurodegenerative diseases
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
313794
0
Treatment: Other
Query!
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.
Query!
Control group
Active
Query!
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.
Query!
Assessment method [1]
319280
0
Query!
Timepoint [1]
319280
0
Adverse events will be assessed every month for 12 months after commencement.
Query!
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.
Query!
Assessment method [2]
319281
0
Query!
Timepoint [2]
319281
0
Physical examination will be assessed at screening, 3 months, 6 months, 9 months and 12 months after commencement.
Query!
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,
Query!
Assessment method [1]
367551
0
Query!
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.
Query!
Secondary outcome [2]
367608
0
Progression of disability using the ALS Functional Rating Scale (ALS FRS-R).
Query!
Assessment method [2]
367608
0
Query!
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).
Query!
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.
Query!
Assessment method [3]
367610
0
Query!
Timepoint [3]
367610
0
Respiratory function will be measured at baseline, at 3 months, 6 months, 9 months and 12 months following commencement.
Query!
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.
Query!
Assessment method [4]
367611
0
Query!
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.
Query!
Secondary outcome [5]
367614
0
Changes in gut microbe levels in faecal samples using DNA sequencing of the faecal microbes.
Query!
Assessment method [5]
367614
0
Query!
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.
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Inability of patient to provide consent
- Inability to swallow capsules
- Participation in another/other clinical trials
- Prohibited concomitant medications: antibiotics, probiotics
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by Stata 15
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Safety/efficacy
Query!
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.
Query!
Recruitment
Recruitment status
Completed
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
30/11/2017
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
6/11/2018
Query!
Date of last data collection
Anticipated
6/12/2019
Query!
Actual
19/11/2019
Query!
Sample size
Target
30
Query!
Accrual to date
Query!
Final
12
Query!
Recruitment in Australia
Recruitment state(s)
QLD
Query!
Recruitment postcode(s) [1]
25856
0
4066 - Auchenflower
Query!
Funding & Sponsors
Funding source category [1]
302112
0
Charities/Societies/Foundations
Query!
Name [1]
302112
0
Wesley Medical Research
Query!
Address [1]
302112
0
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive, Auchneflower, Queensland, 4066
Query!
Country [1]
302112
0
Australia
Query!
Primary sponsor type
Charities/Societies/Foundations
Query!
Name
Wesley Medical Research
Query!
Address
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive, Auchneflower, Queensland, 4066
Query!
Country
Australia
Query!
Secondary sponsor category [1]
301944
0
None
Query!
Name [1]
301944
0
Query!
Address [1]
301944
0
Query!
Country [1]
301944
0
Query!
Ethics approval
Ethics application status
Approved
Query!
Ethics committee name [1]
302791
0
UnitingCare Health Human Research Ethics Committee
Query!
Ethics committee address [1]
302791
0
The Wesley Hospital
PO Box 499
Auchenflower, Queensland 4066
Query!
Ethics committee country [1]
302791
0
Australia
Query!
Date submitted for ethics approval [1]
302791
0
22/08/2017
Query!
Approval date [1]
302791
0
21/11/2017
Query!
Ethics approval number [1]
302791
0
1741
Query!
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.
Query!
Trial website
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
91418
0
Prof Pamela McCombe
Query!
Address
91418
0
UQCCR
Building 71/918
Royal Brisbane Women’s Hospital
Herston QLD 4029
Query!
Country
91418
0
Australia
Query!
Phone
91418
0
+61 7 33466017
Query!
Fax
91418
0
Query!
Email
91418
0
[email protected]
Query!
Contact person for public queries
Name
91419
0
Dr Kelley Foster
Query!
Address
91419
0
Wesley Medical Research
8th Floor, East Wing, The Wesley Hospital
451 Coronation Drive
Auchenflower, Queensland, 4066
Query!
Country
91419
0
Australia
Query!
Phone
91419
0
+61 7 37211503
Query!
Fax
91419
0
Query!
Email
91419
0
[email protected]
Query!
Contact person for scientific queries
Name
91420
0
Prof Pamela McCombe
Query!
Address
91420
0
UQCCR
Building 71/918
Royal Brisbane Women’s Hospital
Herston QLD 4029
Query!
Country
91420
0
Australia
Query!
Phone
91420
0
+61 7 33466017
Query!
Fax
91420
0
Query!
Email
91420
0
[email protected]
Query!
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
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.
Download to PDF