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Trial registered on ANZCTR


Registration number
ACTRN12620000236998
Ethics application status
Approved
Date submitted
13/02/2020
Date registered
25/02/2020
Date last updated
25/02/2020
Date data sharing statement initially provided
25/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating sodium selenate as a treatment for behavioural variant frontotemporal dementia
Scientific title
A Phase 2b Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Possible Behavioural Variant Fronto-temporal Dementia
Secondary ID [1] 300547 0
Nil known
Universal Trial Number (UTN)
U1111-1248-2724
Trial acronym
SEL002
Linked study record

Health condition
Health condition(s) or problem(s) studied:
behavioural variant frontotemporal dementia 316273 0
Condition category
Condition code
Neurological 314552 314552 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sodium selenate (15 mg three times a day) 52 weeks oral tablet.
Participants will be asked to return unused medications at clinic visits, which will be counted by study personnel to measure compliance. Telephone calls during the early part of the trial will be made to remind participants/study partners of dosing regimen to ensure participant's are taking the medication as instructed.
Intervention code [1] 316850 0
Treatment: Drugs
Comparator / control treatment
Placebo - microcellulose tablet
Control group
Placebo

Outcomes
Primary outcome [1] 322874 0
To assess the efficacy of a supranutritional dose of sodium selenate (Na2SeO4) in patients with behavioural variant frontotemporal dementia (bvFTD), as measured by change in global brain volume.
Global brain volume will be measured on MRI brain, using SIENA and SIENAX - open source imaging software which measures total brain volume.
Timepoint [1] 322874 0
52 weeks post-initiation of treatment
Secondary outcome [1] 380100 0
To assess the safety and tolerability of sodium selenate in patients with behavioural variant frontotemporal dementia.
Safety and tolerability will be measured by the frequency and severity of adverse events, anf the rate of study withdrawal.
Dairy cards will be used to record adverse events (solicited and unsolicited) between clinical visits. Safety laboratory tests, 12-lead ECG, physical and neurological examinations will be conducted at clinical visits. In the event of a clinically significant abnormality being detected, this will be recorded as an adverse event.
Known side effects of sodium selenate treatment include; headache, nausea, lethargy, fatigue, alopecia (mild), nail changes and muscle cramps. All adverse events are mild and reversible.
Timepoint [1] 380100 0
52 weeks post-initiation of treatment
Secondary outcome [2] 380101 0
To assess the effect of sodium selenate on cerebrospinal fluid total tau levels in patients with behavioural variant frontotemporal dementia.
Cerebrospinal fluid will be sampled via lumbar puncture at baseline and week 52. Levels of tau protein in the sample will be measured using a specific lab protocol for measuring tau.

Timepoint [2] 380101 0
52 weeks post-initiation of treatment
Secondary outcome [3] 380102 0
To assess the effect of sodium selenate on cognitive function as measured by the Addenbrooke’s Cognitive Examination (ACE-III) in patients with behavioural variant frontotemporal dementia.
Timepoint [3] 380102 0
52 weeks post-initiation of treatment
Secondary outcome [4] 380103 0
To assess the effect of sodium selenate on behaviour as measured by the Cambridge Behavioural Inventory (CBI-R) in patients with behavioural variant frontotemporal dementia.
Timepoint [4] 380103 0
52 weeks post-initiation of treatment

Eligibility
Key inclusion criteria
Inclusion criteria
1. Male or female (age 35 years or older). All participants must be using effective contraception for the duration of the trial and for 4 weeks following cessation of the investigational medicinal product (IMP). Female participants of non-childbearing potential must be either surgically sterile (hysterectomy and/or oophorectomy) or postmenopausal at least 1 year. All female participants must have a negative plasma hCG pregnancy test at screening.
2. Modified Hachinski Ischaemia Score less than or equal to 4 (Moroney et al., 1997)
3. Subjects must have a diagnosis of possible or probable bvFTD established in accordance with the recommendations from the International Behavioural Variant FTD Criteria Consortium (Rascovsky et al., 2011).
4. Subjects must have a lumbar puncture performed within 14 days prior to Baseline (Visit 2).
5. Subject must have an MRI scan during the screening period and prior to Baseline (Visit 2), with no gross structural abnormality indicative of a neurological disorder other than bvFTD.
6. Subject must be living in the community and have at least 10 contact hours per week with a responsible carer. The carer should be capable of ensuring the subject's compliance with the medication, be prepared to attend with the subject for assessment and be willing to participate in completing the various assessments throughout the period of the subject’s involvement in the Study.
7. Written informed consent must be obtained from the subject or legally authorised representative (as required by local laws and regulations), and the participant’s carer.
8. Subjects must have a negative amyloid-binding PET scan. Historical scans will be accepted. In patients who have not previously had an amyloid-PET this will be performed during the screening period and prior to Baseline (Visit 2).
Minimum age
35 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has participated in a clinical investigation of a medication or device within the 3 months prior to the Screening Visit (Visit 1), with the exception of prior exposure to sodium selenate.
2. Subject in whom a lumbar puncture is contra-indicated.
3. Subject with a history of alcohol and/or drug abuse, defined as meeting DSM-V criteria for substance use disorder. This applies to alcohol and/or any illicit drug, including cannabis within the 6 months prior to the Screening Visit (Visit 1).
4. Subject who is unlikely to comply with trial visit schedule or with trial medication.
5. Subject has a known sensitivity to selenium, sodium selenate, any medicine or vitamin containing sodium selenate, similar agents or any of the excipients (including microcrystalline cellulose) used.
6. Subject has a primary, secondary or pseudodementia condition other than possible bvFTD, or has current evidence or history of neurological, psychiatric or any other illness that could contribute to cognitive impairment.
7. Subject has a known history of familial Alzheimer’s Disease.
8. Subject has a known genetic form of frontotemporal dementia that is not considered a primary tauopathy (e.g. positive for the C9ORF72 gene).
9. Subject has a significant medical or neurological disease, with the exception of bvFTD that:
• is not adequately controlled by therapy; and/or
• in the opinion of the investigator may interfere with the patient’s ability to complete the study or might impact on the patient’s cognitive performance.
10. Subject has current evidence of unstable diabetes.
11. Subject has significant impairment of any of the following for the age of the subject, which may compromise safety of the subject/validity of the data:
• Renal function (i.e. estimated glomerular filtration rate (eGFR) <30 ml/min)
• Hepatic function (i.e. abnormal liver function tests greater than 2 x upper limit of normal)
• Haematological function.
12. Subject in whom it is anticipated that there will be a definite indication for the commencement of other licensed anti-dementia drug treatment within the 64-week period of trial participation.
13. Subject is currently taking one of the following drugs, or has taken one of the following drugs within the 6 weeks prior to the Screening Visit (Visit 1):
• Memantine, or other NMDA receptor antagonists (such as amantadine, ketamine, dextromethorphan or nitrous oxide)
• Oral and/or injectable steroids, for example dexamethasone, fludrocortisone , methylprednisolone, prednisolone or prednisone
14. Subject is currently taking any of the following:
• Digoxin, phenobarbitone, warfarin or any other medication that has a narrow margin between effective dose and toxic dose or between effective dose and ineffective dose, where the subject would be at risk if the levels were elevated or fell due to interaction with sodium selenate.
15. Subject has started taking or changed their dose of other medication known to have an effect on mood or cognition within the 4 weeks prior to the Screening Visit (Visit 1). Examples of such drugs include:
• Anticholinergics, for example ipratropium, oxitropium or tiotropium bromide
• Hypnotics, sedatives and anxiolytics, for example barbiturates, benzodiazepines, serotonin 1A agonists, hydroxyzine, zolpidem or zopiclone
• Antidepressants, for example tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitor (MAOIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), noradrenergic and specific serotonergic antidepressants, buspirone, reboxetine or trazodone
• Antiepileptics, for example barbiturates, benzodiazepines, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, primidone, topiramate, valproate or vigabatrin
• Antipsychotics, for example butyrophenones, phenothiazines, thioxanthenes, amisulpride, aripiprazole, clozapine, olanzapine, paliperidone or quetiapine
• Memory-enhancing drugs, for example aniracetam, oxiracetam, piracetam or pramiracetam
• Nutraceutical such as Souvenaid, and other supplements which contain selenium

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 involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical power has thus been determined on the primary outcome variable (percentage brain volume change; PBVC). Previous studies indicate that the mean annual rate of PBVC in FTD is 3.15% (SD = 2.08). The mean atrophy rate in controls is 0.47%. A sample size of 120 patients would render the study sensitive to a medium effect size (Cohen’s d = 0.50, alpha = 5%, power = 80%). This would be equivalent to detecting a 2.10% rate of decline, which is a 44% decline in atrophy. This would represent a clinically meaningful treatment effect.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW,VIC
Recruitment hospital [1] 15877 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 15878 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 15879 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 15880 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 29334 0
3050 - Parkville
Recruitment postcode(s) [2] 29335 0
2050 - Camperdown
Recruitment postcode(s) [3] 29336 0
3128 - Box Hill
Recruitment postcode(s) [4] 29337 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304959 0
Government body
Name [1] 304959 0
NHMRC
Address [1] 304959 0
16 Marcus Clarke St,
Canberra ACT 2601
Country [1] 304959 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne
3004 VIC
Country
Australia
Secondary sponsor category [1] 305320 0
None
Name [1] 305320 0
Address [1] 305320 0
Country [1] 305320 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305369 0
Alfred Health HREC
Ethics committee address [1] 305369 0
55 Commercial Road
Melbourne
VIC 3004
Ethics committee country [1] 305369 0
Australia
Date submitted for ethics approval [1] 305369 0
Approval date [1] 305369 0
18/12/2019
Ethics approval number [1] 305369 0

Summary
Brief summary
This study will investigate a new drug, sodium selenate, for the treatment of behavioural variant frontotemporal dementia (bvFTD). Up to 120 patients with bvFTD will be recruited in to the study. Half of the patients will receive 52 weeks of treatment with sodium selenate (15 mg three times a day), and the other half a placebo (a sugar pill). The main outcome of the study will be the change in brain volume over 52 weeks, comparing the treatment group to the placebo group. Additional outcomes will look at the overall safety and tolerability of the treatment, the levels of tau (a protein involved in the development of bvFTD) in the cerebrospinal fluid, the rate of cognitive decline and changes in behavioural symptoms observed in patients over the 52 weeks of treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100142 0
Prof Terence O'Brien
Address 100142 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 100142 0
Australia
Phone 100142 0
+61 03 9903 0855
Fax 100142 0
Email 100142 0
te.obrien@alfred.org.au
Contact person for public queries
Name 100143 0
Dr Lucy Vivash
Address 100143 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 100143 0
Australia
Phone 100143 0
+61 03 9903 0860
Fax 100143 0
Email 100143 0
l.vivash@alfred.org.au
Contact person for scientific queries
Name 100144 0
Dr Lucy Vivash
Address 100144 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 100144 0
Australia
Phone 100144 0
+61 03 9903 0860
Fax 100144 0
Email 100144 0
l.vivash@alfred.org.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?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 6911 0
Study protocol
Citation [1] 6911 0
Link [1] 6911 0
Email [1] 6911 0
Other [1] 6911 0
Available prior to study commencement
Attachment [1] 6911 0
Type [2] 6912 0
Statistical analysis plan
Citation [2] 6912 0
Link [2] 6912 0
Email [2] 6912 0
Other [2] 6912 0
Available prior to study commencement
Attachment [2] 6912 0
Type [3] 6913 0
Informed consent form
Citation [3] 6913 0
Link [3] 6913 0
Email [3] 6913 0
Other [3] 6913 0
Available prior to study commencement
Attachment [3] 6913 0
Type [4] 6914 0
Ethical approval
Citation [4] 6914 0
Link [4] 6914 0
Email [4] 6914 0
Other [4] 6914 0
Available prior to study commencement
Attachment [4] 6914 0
Summary results
No Results