Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset

Summary

The purpose of this study is to qualify the biomarker risk algorithm for prognosis of the risk of developing Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD), and also to evaluate the efficacy of pioglitazone compared with placebo to delay the onset of MCI-AD in cognitively-normal participants who are at high-risk for developing MCI within 5 years.

Timeline

Start

2013-08-01

Primary completion

2018-07-24

Completion

2018-09-06

Outcome

Missed primary endpoint

Stopped: “Lack of efficacy of the drug; no safety concern”

registry analysis (superiority test); High Risk Placebo vs High Risk Pioglitazone; p = 0.307; Regression, Cox NCT01931566 ↗

paper Pioglitazone did not delay the onset of mild cognitive impairment. PMID 34146512 ↗

release “TOMMORROW trial has been terminated. The decision to discontinue the trial was based on a planned interim futility analysis, which showed an inadequate treatment effect” takeda.com ↗

Publications

• Zou H, Luo S, Liu H, Lutz MW, Bennett DA, Plassman BL, Welsh-Bohmer KA. Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study. J Prev Alzheimers Dis. 2023;10(4):886-894. doi: 10.14283/jpad.2023.115.
• Burns DK, Alexander RC, Welsh-Bohmer KA, Culp M, Chiang C, O'Neil J, Evans RM, Harrigan P, Plassman BL, Burke JR, Wu J, Lutz MW, Haneline S, Schwarz AJ, Schneider LS, Yaffe K, Saunders AM, Ratti E; TOMMORROW study investigators. Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021 Jul;20(7):537-547. doi: 10.1016/S1474-4422(21)00043-0.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pioglitazone	Small molecule	0.8 mg	Oral

Indications