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.

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.

Trial Registration: Clinical Trial NCT03228498. Registered 25 July 2017.