scholarly journals A phase 1B open‐labelled study of sodium selenate as a disease modifying treatment for possible behavioural variant fronto‐temporal dementia

2020 ◽  
Vol 16 (S9) ◽  
Author(s):  
Lucy E. Vivash ◽  
Charles B. Malpas ◽  
Dennis Velakoulis ◽  
Terence O’Brien
Keyword(s):  
Sodium Selenate ◽  
Phase 1B ◽  
Disease Modifying ◽  
Disease Modifying Treatment

scholarly journals A phase 1b open label study of sodium selenate as a disease‐modifying treatment for behavioural variant fronto‐temporal dementia

2021 ◽  
Vol 17 (S9) ◽  
Author(s):  
Lucy E Vivash ◽  
Charles B Malpas ◽  
Christopher M Hovens ◽  
Dennis Velakoulis ◽  
Terence O’Brien
Keyword(s):  
Sodium Selenate ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Phase 1B ◽  
Disease Modifying ◽  
Disease Modifying Treatment

scholarly journals Sodium selenate as a disease-modifying treatment for mild–moderate Alzheimer’s disease: an open-label extension study

2021 ◽  
Vol 3 (2) ◽  
pp. e000223
Author(s):  
Lucy Vivash ◽  
Charles B Malpas ◽  
Christopher M Hovens ◽  
Amy Brodtmann ◽  
Steven Collins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Extension Study ◽  
Sodium Selenate ◽  
Cognitive Measures ◽  
Open Label ◽  
Open Label Extension ◽  
Disease Modifying ◽  
Disease Modifying Treatment

IntroductionSodium selenate is a potential disease-modifying treatment for Alzheimer’s disease (AD) which reduces hyperphosphorylated tau through activation of the protein phosphatase 2A enzyme. We have shown sodium selenate to be safe and well tolerated in a 24-week, phase 2a double-blind placebo-controlled randomised controlled trial (RCT), also reporting sodium selenate reduced neurodegeneration on diffusion-weighted MRI. This study assessed the safety and tolerability of chronic sodium selenate treatment (up to 23 months) in patients with AD who had been enrolled in the RCT. Cognitive measures served as secondary outcomes of potential disease-modification.MethodsAn open-label extension study of sodium selenate (10 mg three times a day) in patients with AD who had completed the previous RCT. Twenty-eight patients were enrolled. Patients were regularly monitored for safety, adverse events (AEs) and protocol compliance. Cognitive tests were administered for measures of disease progression.ResultsSixteen patients were discontinued by the sponsor, and 12 discontinued for other reasons. Treatment duration ranged from 6 to 23 months. The majority of AEs were mild (83%), and 33% were treatment-related. Common treatment-related AEs were alopecia (21%) and nail disorder (32%), which both resolved either prior to or following cessation of treatment. Two serious AEs occurred, which were not treatment-related. Alzheimer’s Disease Assessment Scale—Cognitive Subscale 11 score increased 1.8 points over 12 months.DiscussionChronic sodium selenate treatment is safe and well tolerated in patients with AD. Cognitive measures suggest a slowing of disease progression though this could not be confirmed as the study was not controlled. Further research into sodium selenate as a treatment for AD is warranted.

scholarly journals A study protocol for a phase II randomised, double-blind, placebo-controlled trial of sodium selenate as a disease-modifying treatment for behavioural variant frontotemporal dementia

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040100
Author(s):  
Lucy Vivash ◽  
Charles B Malpas ◽  
Leonid Churilov ◽  
Mark Walterfang ◽  
Amy Brodtmann ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Brain Volume ◽  
Controlled Trial ◽  
Analysis Of Covariance ◽  
Primary Study ◽  
Sodium Selenate ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Disease Modifying ◽  
Disease Modifying Treatment

IntroductionBehavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder often neuropathologically associated with the accumulation of abnormally hyperphosphorylated tau, for which there is currently no disease-modifying treatment. Previous work by our group has shown sodium selenate upregulates the activity of protein phosphatase 2 in the brain, increasing the rate of tau dephosphorylation. The objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying treatment for bvFTD.Methods and analysisThis will be a multisite, phase IIb, double-blind placebo-controlled trial of sodium selenate. One hundred and twenty participants will be enrolled across 4 Australian academic hospitals. Following screening eligible participants will be randomised (1:1) to sodium selenate (15 mg three times a day) or placebo for 52 weeks. Participants will have regular safety and efficacy visits throughout the study period. The primary study outcome will be percentage brain volume change (PBVC) as measured on MRI over 52 weeks of treatment. This will be analysed with a general linear model (analysis of covariance (ANCOVA)) with the PBVC as an output, the treatment as an input and the baseline brain volume as covariate for adjustment purposes. Secondary outcomes include safety and tolerability measures, and efficacy measures; change in cerebrospinal fluid total-tau, Addenbrooke’s Cognitive Examination-III and Cambridge Behavioural Inventory-Revised scores over the 52 weeks of treatment. These will also be analysed with ANCOVA where the corresponding baseline measure will be incorporated in the model. Additional exploratory outcomes will include other imaging, cognitive and biospecimen analyses.Ethics and disseminationThe study was approved by the Human Research and Ethics Committee of the lead site as part of the Australian Multisite Ethics approval system. The results of the study will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberACTRN12620000236998 .

scholarly journals Relapse recovery in multiple sclerosis: Effect of treatment and contribution to long-term disability

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110155
Author(s):  
Marinos G Sotiropoulos ◽  
Hrishikesh Lokhande ◽  
Brian C Healy ◽  
Mariann Polgar-Turcsanyi ◽  
Bonnie I Glanz ◽  
...  
Keyword(s):  
Functional System ◽  
Older Age ◽  
Lesion Volume ◽  
Clinical Predictors ◽  
Disability Status ◽  
Bladder Symptoms ◽  
Disease Modifying ◽  
Disease Modifying Treatment ◽  
Baseline Bmi

Background Although recovery from relapses in MS appears to contribute to disability, it has largely been ignored as a treatment endpoint and disability predictor. Objective To identify demographic and clinical predictors of relapse recovery in the first 3 years and examine its contribution to 10-year disability and MRI outcomes. Methods Relapse recovery was retrospectively assessed in 360 patients with MS using the return of the Expanded Disability Status Scale (EDSS), Functional System Scale and neurologic signs to baseline at least 6 months after onset. Univariate and multivariable models were used to associate recovery with demographic and clinical factors and predict 10-year outcomes. Results Recovery from relapses in the first 3 years was better in patients who were younger, on disease-modifying treatment, with a longer disease duration and without bowel or bladder symptoms. For every incomplete recovery, 10-year EDSS increased by 0.6 and 10-year timed 25-foot walk increased by 0.5 s. These outcomes were also higher with older age and higher baseline BMI. Ten-year MRI brain atrophy was associated only with older age, and MRI lesion volume was only associated with smoking. Conclusions Early initiation of disease-modifying treatment in MS was associated with improved relapse recovery, which in turn prevented long-term disability.

Planning and approach to allergen-specific immunotherapy in polyallergic patients

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 577-585
Author(s):  
Nerin N Bahceciler ◽  
Ozel Yuruker
Keyword(s):  
Clinical Management ◽  
Respiratory Diseases ◽  
Specific Immunotherapy ◽  
Clinical Symptoms ◽  
Allergen Specific Immunotherapy ◽  
Stepwise Approach ◽  
Future Studies ◽  
Disease Modifying ◽  
Management Recommendations ◽  
Disease Modifying Treatment

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

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