Abstract / Summary
Introduction: Stroke patients are at a higher risk of developing cognitive difficulties. Insulin resistance has been identified as a risk factor for decline in cognition, raising the possibility that pioglitazone, an insulin-sensitizing agent, might benefit stroke patients with cognitive impairment by improving insulin sensitivity.
Methods: In this single-center, double-blind, randomized controlled trial, 131 eligible patients with post-stroke cognitive impairment were randomized to receive either standard therapy plus pioglitazone (15 mg once daily) or standard therapy alone plus matching placebo. Of the 131 randomized participants, 111 completed the study and were included in the per-protocol analysis.
Results: No statistically significant between-group differences were observed for the primary outcomes, including the Montreal Cognitive Assessment (MoCA) score (p = 0.057), P300 latency (ms) (p = 0.64), P300 amplitude (μV) (p = 0.321), and plasma Aβ42/Aβ40 ratio (p = 0.26). Furthermore, 25 (45.5%) participants in the intervention arm and 13 (23.2%) participants in the control arm experienced at least one Adverse Drug Reaction (ADR) (p = 0.63).
Discussion: The study findings indicated that a low dose of pioglitazone did not significantly improve cognitive function over a 12-month period. The proposed neuroprotective effects of pioglitazone reported in previous studies were not reflected in the outcomes assessed in this trial.
Conclusion: Among stroke patients with cognitive impairment, pioglitazone as an add-on therapy did not significantly improve cognitive function as measured by MoCA scores, P300 Event-Related Potentials (ERPs), and plasma amyloid-beta biomarkers over a 1-year period. (Clinical Trial number: CTRI2024/09/074281) (Date of registration: 24/09/2024).