Category: Parkinson’s Disease: Clinical Trials
Objective: To assess the therapeutic effect of DL-3-n-butylphthalide on cognitive impairment associated with Parkinson’s disease (PD).
Background: PD associated cognitive impairment are attracting attention because of its great impact on patients’ quality of life. Also, with the increasing number of patients receiving deep brain stimulation (DBS) surgery, the cognitive impairment in some patients has gradually aroused concern. While there is an embarrassing lack of drugs effectively improving early PD cognitive impairment. The dopamine, chronic cerebral ischemia, glutaminergic system and noradrenergic system are reported to be involved in the pathogenesis of PD cognitive impairment. Based on the multi-target effect of DL-3-n-butylphthalide (NBP) and its therapeutic effect on vascular cognitive impairment, we speculate that NBP might exert a disease-modifying effect on cognitive impairment associated with PD.
Method: In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 18-80 years who had a diagnosis of mild cognitive impairment due to PD progression at 10 academic medical centers in China. Inclusion criteria included a Montreal Cognitive Assessment (MOCA) score ≥20 and ≤25 and for patients undergoing DBS surgery, a MOCA score ≥26 before surgery is required. Besides, all enrolled patients received stable dopaminergic medicine without drugs affecting cognitive function. Patients were randomly assigned to NBP 200 mg three times daily or matched placebo (1:1) for 48 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in MOCA and mini-mental state examination (MMSE) after 48 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population.
Results: This study enrolled 287 patients. NBP showed greater effects than placebo on MOCA (NBP change 1.74 vs. placebo 0.90; P=0.0059; ITT) and MMSE (NBP change 1.00 vs. placebo 0.19; P=0.0001; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms.
Conclusion: Over the 12-month treatment period, NBP was effective for improving cognitive functioning in patients with PD and exhibited good safety.
To cite this abstract in AMA style:
C. Han, Y. Xia, J. Wu, Y. Sun, L. Kou, J. Huang, Q. Wang, E. Xu, H. Yu, Q. Ye, X. Luo, H. Ma, H. Chen, L. Wang, T. Wang. The effects of DL-3-n-butylphthalide in patients with mild cognitive impairment due to Parkinson’s disease: A multicenter, randomized, double-blind, placebo-controlled trial [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/the-effects-of-dl-3-n-butylphthalide-in-patients-with-mild-cognitive-impairment-due-to-parkinsons-disease-a-multicenter-randomized-double-blind-placebo-controlled-trial/. Accessed June 14, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effects-of-dl-3-n-butylphthalide-in-patients-with-mild-cognitive-impairment-due-to-parkinsons-disease-a-multicenter-randomized-double-blind-placebo-controlled-trial/