Efficacy and Safety of the Association of Nimodipine and Choline Alphoscerate in the Treatment of Cognitive Impairment in Patients with Cerebral Small Vessel Disease. The CONIVaD Trial

Abstract

Background No approved treatment is available for patients with vascular cognitive impairment (VCI) due to cerebral small vessel disease (SVD). Objective The CONIVaD (Choline Alphoscerate and Nimodipine in Vascular Dementia) study aimed to investigate the feasibility, efficacy, and safety of a combined treatment with choline alphoscerate and nimodipine in patients with SVD and mild-to-moderate cognitive impairment. Methods Within this pilot, single-center (university hospital), double-blinded, randomized clinical trial, patients were randomized to two arms: 1-year treatment with nimodipine 30 mg three times a day (TID) plus choline alphoscerate 600 mg twice a day (BID) (arm 1) or nimodipine 30 mg TID plus placebo BID (arm 2). Patients underwent an evaluation at baseline and after 12 months. Cognitive decline, defined as a ≥ 2-point loss on the Montreal Cognitive Assessment, was the primary endpoint. Functional, quality of life, other cognitive measures, and safety were secondary endpoints. Treatment adherence was measured by the count of medicine bottles returned by patients. Results Sixty-two patients were randomized (31 each arm). Fourteen patients (22%) dropped out for reasons including consent withdrawal (n = 9), adverse reactions (n = 4), and stroke (n = 1). Forty-eight patients (mean ± SD age 75.1 ± 6.8 years), well balanced between arms, completed the study. Regarding adherence, of the prescribed total drug dose, > 75% was taken by 96% of patients for choline alphoscerate, 87.5% for placebo, and 15% for nimodipine. No statistically significant differences were found between the treatment groups for the primary cognitive outcome, nor for the secondary outcomes. Eight patients had non-serious adverse reactions; five presented adverse events. Conclusion Patients' adherence to treatment was low. With this limitation, the combined choline alphoscerate-nimodipine treatment showed no significant effect in our cohort of VCI patients with SVD. The safety profile was good overall.

Clinical efficacy of idebenone in stroke patients with mild cognitive impairment, and its effect on regional homogeneity of resting-state functional magnetic resonance imaging of the brain

“…It is highly lipid-soluble, and it easily crosses the blood-brain barrier, resulting in better distribution of its bioactive form in the intracranial tissues than other calcium antagonists, as well as enhanced effect in the perivascular region of the brain. Previous research has shown that nimodipine produced significant differences between pre-and posttreatment temporal orientation, memory, calculation, and decision-making parameters in patients with mild PSCI, before and after treatment [17]. Cochrane used nimodipine at a dose of 90 mg/day for 12 -24 weeks, produced a 39 % reduction in cognitive decline, with significant improvements in memory, attentiveness, orientation, and mood swings, thereby providing a rationale for the use of the drug [18].…”

Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis

“…All of the included studies (eight studies) were 278 conducted between 1993 and 2022 in Russia (one 279 study) [29], Italy (six studies) [30][31][32][33][34][35], and Mexico (one study) [36] (Table 1). In four RCTs, ␣-GPC was combined with the cholinesterase inhibitor (ChE-I) donepezil [30,31,33,35].…”

“…In four RCTs, ␣-GPC was combined with the cholinesterase inhibitor (ChE-I) donepezil [30,31,33,35]. In one RCT, ␣-GPC was evaluated in combination with nimodipine [34], and the effects of ␣-GPC were examined in three RCTs without any combination of treatments [29,32,36].…”

“…1). One of 274 the included studies was a prospective cohort study 275 [29], and the other seven were RCTs [30][31][32][33][34][35][36].…”

Effect of Choline Alphoscerate on the Survival of Glioblastoma Patients: A Retrospective, Single-Center Study

“…GPC, a choline precursor, increases and releases acetylcholine (ACh) to enhance cholinergic transmission [ 8 , 9 , 10 ]. Since GPC is well tolerated with adequate central nervous system penetration [ 11 ], recent investigations have proved that GPC has some positive effects on cognitive improvement in various clinical settings [ 12 , 13 ]. Although the guideline for the pharmacological approach has not been established, many neuro-oncologists have worried about the decline of cognitive function caused by treatments or disease progression and prescribed several drugs [ 14 ].…”