Participants receiving the iron-binding drug deferiprone showed accelerated cognitive decline compared with those receiving placebo in a phase II clinical trial, according to a new study.

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 nine Australian sites between 2018 and 2023. The 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: –0.80, 95% confidence interval [CI] = –0.98 to –0.62 vs placebo: –0.30, 95% CI = –0.54 to –0.06; β for interaction = –0.50, 95% CI = –0.80 to –0.20, P = .002).

Brain imaging in 33 participants confirmed deferiprone reduced hippocampal iron levels compared with placebo (change = deferiprone: –0.36 ppb, 95% CI = –0.76 to 0.04 ppb vs placebo: 0.32 ppb, 95% CI = –0.12 to 0.75 ppb; β for interaction = –0.68, 95% CI = –1.27 to –0.09, P = .03).

The trial recorded a 37.7% discontinuation rate in the deferiprone group vs 25.0% 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 73.0 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.