Investigating sodium selenate as a treatment for behavioural variant frontotemporal dementia
A Phase 2b Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Possible Behavioural Variant Fronto-temporal Dementia
Alfred Health
120 participants
Aug 17, 2021
Interventional
Conditions
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.
Eligibility
Inclusion Criteria7
- 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.
- Modified Hachinski Ischaemia Score less than or equal to 4 (Moroney et al., 1997)
- Subjects must have a diagnosis of possible or probable bvFTD or PNFA (nfPPA) established in accordance with the recommendations from the International Behavioural Variant FTD Criteria Consortium (Rascovsky et al., 2011) or PPA working group criteria (Gorno-Tempini et al, 2011).
- 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/PNFA.
- 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.
- 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.
- Subjects must have a documented amyloid-binding PET scan, either historical or performed during the screening period and prior to Baseline (Visit 1) that is not consistent with Alzheimer's disease or another neurological disease other than frontotemporal lobar degeneration.
Exclusion Criteria27
- 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.
- Subject in whom a lumbar puncture is contra-indicated.
- 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).
- Subject who is unlikely to comply with trial visit schedule or with trial medication.
- 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.
- Subject has a primary, secondary or pseudodementia condition other than possible bvFTD or PNFA, or has current evidence or history of neurological, psychiatric or any other illness that could contribute to cognitive impairment.
- Subject has a known history of familial Alzheimer’s Disease.
- Subject has a known genetic form of frontotemporal dementia that is not considered a primary tauopathy (e.g. positive for the C9ORF72 gene).
- Subject has a significant medical or neurological disease, with the exception of bvFTD or PNFA 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.
- Subject has current evidence of unstable diabetes.
- 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.
- 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.
- 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.
- 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
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Interventions
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.
Locations(5)
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ACTRN12620000236998