Add-On Citicoline May Improve Motor Function in PD

TOPLINEAddition of citicoline to stable dopaminergic treatment was well tolerated and associated with increased odds of achieving clinically meaningful improvement in motor function among patients with Parkinson’s disease (PD), a trial showed.METHODOLOGYResearchers conducted a randomized, double-blind, parallel-group, multicenter trial (CITIPARK) across 44 Italian outpatient neurology and geriatric clinics. The trial included 474 participants with idiopathic PD who were aged 55 years or older and had a Hoehn and Yahr stage of 1.5-3. Participants were required to be on stable levodopa and other dopaminergic therapies for more than 4 weeks before the baseline visit, have no motor fluctuations or dyskinesias, and have no changes to their medications throughout the study duration. Participants were randomly assigned 2:1 to receive add-on intramuscular citicoline (1000 mg/d; n = 303) or placebo (n = 171) over a 24-week study period, consisting of two 6-week treatment cycles, each followed by a 6-week washout interval. Due to treatment adherence problems during the COVID pandemic, a modified intention-to-treat (mITT) subgroup (citicoline, 127 patients; placebo, 76 patients) was identified to isolate citicoline’s treatment effects among participants who fully completed the regimen. The primary endpoint was the change in the Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score between baseline and week 24 after adjustment for age, sex, and clinical characteristics. Secondary endpoints included changes in scores on the MDS-UPDRS subscales (parts 1-3), EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, PD Questionnaire-39 (PDQ-39), Clinical Global Impression (CGI) scales II and III, and the Non-Motor Symptom Scale (NMSS), as well as safety assessments.TAKEAWAYAdd-on citicoline was not associated with a significant change in the MDS-UPDRS total score at 24 weeks compared with placebo after adjustment. However, among participants in the mITT population, a greater proportion in the citicoline group than in the placebo group achieved a minimal clinically important difference (≥ 3 points) in the MDS-UPDRS total score (52% vs 38.2%; adjusted odds ratio, 2.06; P = .031).The mITT citicoline group showed significantly greater improvement in motor function, as assessed using MDS-UPDRS part 3, than the placebo group at week 24 (change in score, -2.97 vs -0.13; P = .009).In the mITT population, citicoline was associated with greater improvement in CGI-II scores (3.26 vs 3.59; P = .021) and CGI-III scores (9.3 vs 10.38; P = .018) than placebo, indicating greater perceived clinical improvement and therapeutic benefit. Changes in the scores on the MDS-UPDRS parts 1 and 2, the EQ-5D-5L questionnaire, PDQ-39, and NMSS were not significantly different between the groups.In the intention-to-treat/safety group (n = 451), 22.1% of participants receiving citicoline and 27.1% receiving placebo reported adverse events; 1.8% of participants in each group reported dyskinesias. No treatment-related serious adverse events were reported in the mITT population. IN PRACTICE“The CITIPARK trial shows for the first time that citicoline may offer meaningful clinical and motor benefits to PD patients that are receiving standard multidrug dopaminergic treatments and are capable of high treatment adherence,” the investigators wrote.SOURCEThe study was led by Massimo Marano, MD, Università Campus Bio-Medico di Roma, Rome, Italy. It was published online on July 29 in Parkinsonism and Related Disorders.LIMITATIONSThe study was limited by relatively short treatment cycles, exclusion of patients with motor fluctuations or dyskinesias, and possible selection bias in the fully compliant mITT subgroup. The trial may also have been underpowered to detect smaller but clinically relevant changes in secondary outcomes.DISCLOSURESThe study was funded by PIAM Farmaceutici S.p.A. Disclosure information for the study investigators is available in the original study publication.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.