Association of nimodipine and choline alphoscerate in the treatment of cognitive impairment in patients with cerebral small vessel disease: study protocol for a randomized placebo-controlled trial-the CONIVaD trial.

BACKGROUND: Vascular cognitive impairment (VCI) is an extremely disabling condition that includes post-stroke dementia and VCI caused by cerebral small vessel disease (SVD). Currently, there is no approved treatment for this condition. Drugs active on the cholinergic pathway have been tested in VCI patients showing positive but limited efficacy. The calcium-antagonist nimodipine also showed some moderate positive effects in VCI patients. AIMS: CONIVaD (choline alphoscerate and nimodipine in vascular dementia) is a pilot, single-center, double-blinded, randomized trial aimed to assess whether the association of choline alphoscerate and nimodipine is more effective than nimodipine alone in reducing cognitive decline in patients with SVD and mild-to-moderate cognitive impairment. METHODS: All patients are evaluated at baseline and after 12 months with: (1) clinical, daily functions, quality of life, and mood assessment and (2) extensive neuropsychological evaluation. After the baseline evaluation, patients are randomly assigned to one of the two arms of treatment: (1) nimodipine 90 mg/die t.i.d plus placebo b.i.d and (2) nimodipine 90 mg t.i.d plus choline alphoscerate 1200 mg/die b.i.d. for a total of 12 months. The primary endpoint is cognitive decline, expressed as the loss of at least two points on the Montreal Cognitive Assessment at 12 months. Secondary endpoints include safety and tolerability, functional, quality of life, and neuropsychological measures. DISCUSSION: CONIVaD study is the first randomized controlled trial to examine the cognitive efficacy of combined choline alphoscerate-nimodipine treatment in VCI patients. Results of this pilot study will serve as a methodological basis for other clinical controlled, multicentric, double-blinded, and randomized trials. TRIAL REGISTRATION: Clinical Trial NCT03228498. Registered 25 July 2017.