Participants receiving the iron-binding drug deferiprone showed accelerated cognitive decline compared with those receiving placebo in a phase 2 clinical trial.

In the double-masked, placebo-controlled trial, published in JAMA Neurology, researchers enrolled 81 participants with amyloid-confirmed mild cognitive impairment or early Alzheimer's disease at 9 Australian sites between 2018 and 2023. Researchers randomly assigned participants in a 2:1 ratio to receive oral deferiprone (15 mg/kg twice daily, n = 53) or placebo (n = 28) for 12 months.

The deferiprone group demonstrated a greater decline on the neuropsychological test battery composite score compared with placebo (change in score: deferiprone –0.8 versus placebo –0.3).

Brain imaging in 33 participants confirmed deferiprone reduced hippocampal iron levels compared with placebo (change in score: deferiprone: –0.36 ppb versus placebo –0.32 ppb.

The trial recorded a 37.7% discontinuation rate in the deferiprone group versus 25% in the placebo group. Four participants receiving deferiprone (7.5%) developed neutropenia, exceeding rates from previous trials (1.6%–4.4%).

Eligible participants were older than 54 years with confirmed amyloid pathology and Mini-Mental State Examination scores of 20 or higher. The deferiprone group's mean age was 73 years, with 54.7% male participants. The placebo group's mean age was 71.6 years, with 60.7% male participants.

The National Health and Medical Research Council of Australia funded the study, with additional support from ApoPharma, which provided the study drug and funding. Study limitations included high dropout rates and reduced sample size for imaging analyses.

Conflict of interest disclosures can be found in the study.