Deferiprone to delay dementia (the 3D trial): Human/Human trials: Other. (7th December 2020)

• Record Type: Journal Article
• Authors: Ayton, Scott; Woodward, Michael; Ellis, Kathryn A.; Lim, Yen Ying; Maruff, Paul T.; Desmond, Patricia M.; Salvado, Olivier; Fazlollahi, Amir; Rowe, Christopher C.; Churilov, Leonid; Bush, Ashley I.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044107
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Potential therapeutic targets for Alzheimer's disease (AD) outside of β‐amyloid are of increased interest. Brain iron has been reported to predict accelerated AD progression when measured using fluid biomarkers (CSF ferritin), quantitative susceptibility mapping MRI, or directly in post‐mortem tissue, and is one potential therapeutic target. Brain iron may contribute to neurodegeneration by becoming pro‐oxidant (e.g. ferroptosis), or by promoting an inflammatory phenotype of microglia. Deferiprone is an orally bioavailable, BBB‐penetrant moderate iron chelating drug approved for the peripheral iron overload in β‐thalassemia. Deferiprone reported promising evidence for disease modification of Parkinson's disease in two phase II studies; here we report the status of a phase IIb clinical trial of deferiprone for AD. Methods: The primary outcome of this trial is to compare the cognitive performance in a neuropsychological test battery of subjects with mild Alzheimer's disease (confirmed using β‐amyloid PET) treated for 12 months with either deferiprone (15 mg/kg) administered orally twice a day or a matching placebo. Secondary outcomes include adverse events (safety analysis), change in brain iron burden measured by quantitative susceptibility mapping MRI (target engagement), and brain volume changes (secondary efficacy measure). 171 participants will be recruited and randomized in a 2:1 ratio (drug:placebo). Results: Ten clinical trial sites have been established in Victoria (6), New South Wales (3), and Western Australia (1). The first patient was randomized in March 2018. As of January 2020, 101 patients have been screened and 45 randomized. 18 patients have completed the treatment protocol of 1 year. Conclusions: The outcome of this trial is scheduled to report in 2021.