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Deferiprone to delay dementia (the 3D trial)
Author(s) -
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.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044107
Subject(s) - deferiprone , medicine , randomized controlled trial , dementia , placebo , adverse effect , cognitive decline , disease , oncology , pathology , thalassemia , alternative medicine
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.