<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03228498</url>
  </required_header>
  <id_info>
    <org_study_id>2015-003188-13</org_study_id>
    <nct_id>NCT03228498</nct_id>
  </id_info>
  <brief_title>Choline Alphoscerate-Nimodipine in Vascular Cognitive Impairment</brief_title>
  <acronym>CONIVAD</acronym>
  <official_title>Pilot Study on the Association Choline Alphoscerate-Nimodipine in Patients With Subcortical Vascular Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero-Universitaria Careggi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MDM S.p.A.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Ospedaliero-Universitaria Careggi</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess whether the combination of choline alphoscerate 1200mg&#xD;
      per day and nimodipine 90mg per day given orally is more effective than the combination&#xD;
      nimodipine placebo in reducing cognitive decline in patients with subcortical vascular&#xD;
      cognitive impairment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cerebrovascular diseases represent the second most common cause of dementia after Alzheimer's&#xD;
      disease. Since cerebrovascular diseases are age-related, an increase in the incidence of this&#xD;
      pathology, due to the aging of the population, is expected.&#xD;
&#xD;
      Vascular cognitive impairment (VCI) embraces a broad-spectrum of cognitive disorders related&#xD;
      to cerebrovascular diseases, from mild cognitive impairment to severe dementia. VCI is an&#xD;
      extremely disabling condition with severe consequences in terms of direct (e.g., clinic&#xD;
      visits, prescriptions, hospital accesses, etc..) and indirect costs (e.g., loss of patient's&#xD;
      and caregiver's productivity, consequent increase in psychological burdens, etc.).&#xD;
&#xD;
      The two main categories of VCI include post-stroke dementia and vascular cognitive impairment&#xD;
      caused by cerebral small vessel disease. Given its great weight in the dementia field, the&#xD;
      interest of the international scientific community is currently focused on small vessel&#xD;
      disease, its neuroradiological definition and its clinical consequences.&#xD;
&#xD;
      Despite these relevant facts, there are no approved therapies for VCI due to small disease.&#xD;
&#xD;
      In the past, several drugs have been tested in patients affected by VCI with variable&#xD;
      results. A large amount of data come from studies performed with drugs approved for the&#xD;
      treatment of Alzheimer's disease (such as acetylcholinesterase inhibitors,&#xD;
      N-methyl-D-aspartate glutamate receptor antagonists, cholinergic precursors, calcium-channel&#xD;
      blockers).&#xD;
&#xD;
      Choline alphoscerate and nimodipine have demonstrated some positive effects in VCI patients,&#xD;
      and a confirmation of this effect in quantitative terms could permit to obtain the&#xD;
      prescribing license for VCI.&#xD;
&#xD;
      It may be possible that a combined treatment with two drugs that act on different targets&#xD;
      could achieve better results in patients affected by subcortical VCI, also in consideration&#xD;
      of the fact that small vessel disease is characterized by a damage of microvessels and&#xD;
      produces a cortical disconnection.&#xD;
&#xD;
      The main objective of this study is to assess whether the combination of choline alphoscerate&#xD;
      1200mg per day and nimodipine 90mg per day given orally is more effective than the&#xD;
      combination of nimodipine and placebo in reducing cognitive decline in patients with&#xD;
      subcortical VCI.&#xD;
&#xD;
      Project design:&#xD;
&#xD;
      The present study is a 2-year prospective, double-blinded, randomized trial. The enrolment&#xD;
      will be carried out at Vascular Cognitive (VASCOG) clinic of the Careggi University Hospital&#xD;
      in Florence, Italy. Sixty-eight patients will be enrolled according to the following&#xD;
      inclusion criteria: 1) Cognitive impairment of mild to moderate degree defined by a Clinical&#xD;
      Deterioration Rating (CDR) score range between 0.5 and 2.0; 2) Evidence on brain MRI of white&#xD;
      matter hyperintensities (leukoaraiosis of moderate or severe degree according to the modified&#xD;
      Fazekas visual scale and/or presence of lacunar infarcts); 3) Consent to participation in the&#xD;
      study.&#xD;
&#xD;
      All enrolled patients will be evaluated at baseline according to the study protocol that&#xD;
      includes: 1) Clinical assessment; 2) Functional, quality of life and mood assessments; 3)&#xD;
      Extensive neuropsychological evaluation.&#xD;
&#xD;
      After baseline assessment, participants will be randomly assigned to one of two arms of&#xD;
      treatment: 1) nimodipine 90 mg/die t.i.d plus placebo b.i.d; 2) nimodipine 90 mg t.i.d plus&#xD;
      choline alphoscerate 1200 mg/die b.i.d. Treatment will be given for a total of 12 months.&#xD;
&#xD;
      Each patient will be followed-up at 6 and 12 months after baseline. During the first&#xD;
      follow-up visit, clinical assessment and evaluation of side effects and compliance to&#xD;
      treatment will be carried out; during the second follow up visit, clinical assessment, an&#xD;
      extensive neuropsychological evaluation, and mood, functional, and quality of life&#xD;
      assessments will be performed according to the baseline protocol.&#xD;
&#xD;
      The primary end point of this study is to assess the cognitive decline, expressed as the loss&#xD;
      of at least 2 points on the Montreal Cognitive Assessment (MoCA) test 12 months after&#xD;
      baseline. A comparative analysis of MoCA test values between two groups will be assessed by&#xD;
      covariate analysis (ANCOVA) introducing in the statistical model these two covariates: arm of&#xD;
      treatment and MoCA test score at the baseline (based on the exploratory nature of this study&#xD;
      the significance level on the covariate arm of treatment is 20%).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2, 2017</start_date>
  <completion_date type="Actual">July 9, 2019</completion_date>
  <primary_completion_date type="Actual">July 9, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blind (Participant, Investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cognitive decline evaluated by the change of MoCA test score compared with Baseline</measure>
    <time_frame>12 months</time_frame>
    <description>Cognitive decline: expressed as the loss of at least 2 points on Montreal Cognitive Assessment (MoCA) test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of selective attention</measure>
    <time_frame>12 months</time_frame>
    <description>Selective attention assessed by means of Color Word Stroop Test (CWST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of divided attention</measure>
    <time_frame>12 months</time_frame>
    <description>Divided attention assessed by means of Trail Making Test (TMT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of maintained attention</measure>
    <time_frame>12 months</time_frame>
    <description>Maintained attention assessed by means of Symbol Digit Modalities Test (SDMT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of memory</measure>
    <time_frame>12 months</time_frame>
    <description>Memory assessed by means of Rey Auditory-Verbal Learning Test (RAVLT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of functional status</measure>
    <time_frame>12 months</time_frame>
    <description>Functional status measured by Disability Assessment for Dementia scale (DAD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of depressive symptoms</measure>
    <time_frame>12 months</time_frame>
    <description>Depressive symptoms assessed by means of Center for Epidemiological Studies Depression scale (CES-D)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of quality of life</measure>
    <time_frame>12 months</time_frame>
    <description>Quality of life assessed by means of Stroke-Adapted Sickness Impact Profile (SA-SIP30)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of drugs' safety and tolerability.</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation of drugs' side effects incidence between two groups of treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Vascular Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Choline alphoscerate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Choline alphoscerate 1200 mg per day and Nimodipine 90 mg per day&#xD;
concomitant administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo and Drug: Nimodipine 90 mg per day only&#xD;
concomitant administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Choline alphoscerate</intervention_name>
    <description>Choline alphoscerate 600 mg b.i.d plus Nimodipine 30 mg t.i.d</description>
    <arm_group_label>Choline alphoscerate</arm_group_label>
    <other_name>Delecit</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo b.i.d plus Nimodipine 30 mg t.i.d</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Cognitive impairment from mild to moderate degree defined by a Clinical Deterioration&#xD;
             Rating (CDR) score range between 0.5 and 2.0.&#xD;
&#xD;
          2. Evidence on brain MRI of white matter hyperintensities (leukoaraiosis of moderate or&#xD;
             severe degree according to the modified Fazekas visual scale and/or presence of&#xD;
             lacunar infarcts).&#xD;
&#xD;
          3. Consent to participation in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Absence of objectionable cognitive impairment or presence of dementia of severe degree&#xD;
             defined by CDR score &gt; 2.0.&#xD;
&#xD;
          2. Unavailability of brain MRI (in case of absolute contraindications, the use of cranial&#xD;
             CT is allowed).&#xD;
&#xD;
          3. Expected poor compliance with the study protocol.&#xD;
&#xD;
          4. Past diagnosis of major depression, schizophrenia, major anxiety syndrome, or manic-&#xD;
             depressive illness.&#xD;
&#xD;
          5. Diagnosis of degenerative cognitive impairment based on clinical and/or&#xD;
             neuroradiological findings (i.e., patients with prevailing memory impairment, or with&#xD;
             medial temporal atrophy on brain MRI in absence of evident vascular abnormalities;&#xD;
             i.e., Alzheimer disease as defined using the National Institute of Neurological and&#xD;
             Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders&#xD;
             Association criteria, Parkinson disease, Huntington disease, frontotemporal dementia).&#xD;
&#xD;
          6. Diagnosis of cognitive impairment from other causes (i.e., vitamine B12 and folic acid&#xD;
             deficiency, thyroid disorders, metabolic diseases, head trauma, tumor or infections of&#xD;
             the central nervous system, normal pressure hydrocephalus).&#xD;
&#xD;
          7. Medical conditions expected to progress, recur, or change to such a degree to&#xD;
             interfere with the assessment of the clinical and mental status.&#xD;
&#xD;
          8. Clinically relevant cardiac or pulmonary insufficiency.&#xD;
&#xD;
          9. Relevant electrocardiograph abnormalities; bradycardia (50 bpm) or tachycardia (120&#xD;
             bpm) under resting conditions.&#xD;
&#xD;
         10. Myocardial infarction within the past 6 months.&#xD;
&#xD;
         11. Stroke still requiring neurological rehabilitation.&#xD;
&#xD;
         12. Severe/untreated blood pressure (systolic 180 mm Hg, diastolic 95 mm Hg).&#xD;
&#xD;
         13. Clinically relevant liver function impairment.&#xD;
&#xD;
         14. Insulin-dependent diabetes mellitus.&#xD;
&#xD;
         15. Idiopathic epilepsy and anti-epileptic treatment.&#xD;
&#xD;
         16. Severe anemia (Hb &lt;10 mg/dL).&#xD;
&#xD;
         17. Severe gastrointestinal disease.&#xD;
&#xD;
         18. Cancer.&#xD;
&#xD;
         19. Known intolerance to study drugs.&#xD;
&#xD;
         20. Coexistent serious illnesses that would imply a drop-out before the end of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Stroke Unit, VAS-COG clinic, Azienda Ospedaliero Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST. Vascular cognitive impairment. Lancet Neurol. 2003 Feb;2(2):89-98. doi: 10.1016/s1474-4422(03)00305-3.</citation>
    <PMID>12849265</PMID>
  </reference>
  <reference>
    <citation>Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689-701. doi: 10.1016/S1474-4422(10)70104-6.</citation>
    <PMID>20610345</PMID>
  </reference>
  <reference>
    <citation>Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013 May;12(5):483-97. doi: 10.1016/S1474-4422(13)70060-7. Erratum In: Lancet Neurol. 2013 Jun;12(6):532.</citation>
    <PMID>23602162</PMID>
  </reference>
  <reference>
    <citation>Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.</citation>
    <PMID>23867200</PMID>
  </reference>
  <reference>
    <citation>Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004 Nov 15;226(1-2):67-70. doi: 10.1016/j.jns.2004.09.014.</citation>
    <PMID>15537523</PMID>
  </reference>
  <reference>
    <citation>Smith EE, Cieslak A, Barber P, Chen J, Chen YW, Donnini I, Edwards JD, Frayne R, Field TS, Hegedus J, Hanganu V, Ismail Z, Kanji J, Nakajima M, Noor R, Peca S, Sahlas D, Sharma M, Sposato LA, Swartz RH, Zerna C, Black SE, Hachinski V. Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment. J Am Heart Assoc. 2017 May 5;6(5):e005568. doi: 10.1161/JAHA.117.005568. No abstract available.</citation>
    <PMID>28476873</PMID>
  </reference>
  <reference>
    <citation>Di Perri R, Coppola G, Ambrosio LA, Grasso A, Puca FM, Rizzo M. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res. 1991 Jul-Aug;19(4):330-41. doi: 10.1177/030006059101900406.</citation>
    <PMID>1916007</PMID>
  </reference>
  <reference>
    <citation>Pantoni L, Carosi M, Amigoni S, Mascalchi M, Inzitari D. A preliminary open trial with nimodipine in patients with cognitive impairment and leukoaraiosis. Clin Neuropharmacol. 1996 Dec;19(6):497-506. doi: 10.1097/00002826-199619060-00003.</citation>
    <PMID>8937788</PMID>
  </reference>
  <reference>
    <citation>Pantoni L, del Ser T, Soglian AG, Amigoni S, Spadari G, Binelli D, Inzitari D. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial. Stroke. 2005 Mar;36(3):619-24. doi: 10.1161/01.STR.0000155686.73908.3e. Epub 2005 Feb 3.</citation>
    <PMID>15692125</PMID>
  </reference>
  <reference>
    <citation>Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991.</citation>
    <PMID>15817019</PMID>
  </reference>
  <reference>
    <citation>Poggesi A, Salvadori E, Pantoni L, Pracucci G, Cesari F, Chiti A, Ciolli L, Cosottini M, Del Bene A, De Stefano N, Diciotti S, Dotti MT, Ginestroni A, Giusti B, Gori AM, Nannucci S, Orlandi G, Pescini F, Valenti R, Abbate R, Federico A, Mascalchi M, Murri L, Inzitari D. Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers-The VMCI-Tuscany Study: Rationale, Design, and Methodology. Int J Alzheimers Dis. 2012;2012:608013. doi: 10.1155/2012/608013. Epub 2012 Apr 8.</citation>
    <PMID>22550606</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 19, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>January 9, 2020</last_update_submitted>
  <last_update_submitted_qc>January 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero-Universitaria Careggi</investigator_affiliation>
    <investigator_full_name>Leonardo Pantoni</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03228498
org study id: 2015-003188-13
nct id: NCT03228498
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to assess whether the combination of choline alphoscerate 1200mg
      per day and nimodipine 90mg per day given orally is more effective than the combination
      nimodipine placebo in reducing cognitive decline in patients with subcortical vascular
      cognitive impairment
Cerebrovascular diseases represent the second most common cause of dementia after Alzheimer's
      disease. Since cerebrovascular diseases are age-related, an increase in the incidence of this
      pathology, due to the aging of the population, is expected.

      Vascular cognitive impairment (VCI) embraces a broad-spectrum of cognitive disorders related
      to cerebrovascular diseases, from mild cognitive impairment to severe dementia. VCI is an
      extremely disabling condition with severe consequences in terms of direct (e.g., clinic
      visits, prescriptions, hospital accesses, etc..) and indirect costs (e.g., loss of patient's
      and caregiver's productivity, consequent increase in psychological burdens, etc.).

      The two main categories of VCI include post-stroke dementia and vascular cognitive impairment
      caused by cerebral small vessel disease. Given its great weight in the dementia field, the
      interest of the international scientific community is currently focused on small vessel
      disease, its neuroradiological definition and its clinical consequences.

      Despite these relevant facts, there are no approved therapies for VCI due to small disease.

      In the past, several drugs have been tested in patients affected by VCI with variable
      results. A large amount of data come from studies performed with drugs approved for the
      treatment of Alzheimer's disease (such as acetylcholinesterase inhibitors,
      N-methyl-D-aspartate glutamate receptor antagonists, cholinergic precursors, calcium-channel
      blockers).

      Choline alphoscerate and nimodipine have demonstrated some positive effects in VCI patients,
      and a confirmation of this effect in quantitative terms could permit to obtain the
      prescribing license for VCI.

      It may be possible that a combined treatment with two drugs that act on different targets
      could achieve better results in patients affected by subcortical VCI, also in consideration
      of the fact that small vessel disease is characterized by a damage of microvessels and
      produces a cortical disconnection.

      The main objective of this study is to assess whether the combination of choline alphoscerate
      1200mg per day and nimodipine 90mg per day given orally is more effective than the
      combination of nimodipine and placebo in reducing cognitive decline in patients with
      subcortical VCI.

      Project design:

      The present study is a 2-year prospective, double-blinded, randomized trial. The enrolment
      will be carried out at Vascular Cognitive (VASCOG) clinic of the Careggi University Hospital
      in Florence, Italy. Sixty-eight patients will be enrolled according to the following
      inclusion criteria: 1) Cognitive impairment of mild to moderate degree defined by a Clinical
      Deterioration Rating (CDR) score range between 0.5 and 2.0; 2) Evidence on brain MRI of white
      matter hyperintensities (leukoaraiosis of moderate or severe degree according to the modified
      Fazekas visual scale and/or presence of lacunar infarcts); 3) Consent to participation in the
      study.

      All enrolled patients will be evaluated at baseline according to the study protocol that
      includes: 1) Clinical assessment; 2) Functional, quality of life and mood assessments; 3)
      Extensive neuropsychological evaluation.

      After baseline assessment, participants will be randomly assigned to one of two arms of
      treatment: 1) nimodipine 90 mg/die t.i.d plus placebo b.i.d; 2) nimodipine 90 mg t.i.d plus
      choline alphoscerate 1200 mg/die b.i.d. Treatment will be given for a total of 12 months.

      Each patient will be followed-up at 6 and 12 months after baseline. During the first
      follow-up visit, clinical assessment and evaluation of side effects and compliance to
      treatment will be carried out; during the second follow up visit, clinical assessment, an
      extensive neuropsychological evaluation, and mood, functional, and quality of life
      assessments will be performed according to the baseline protocol.

      The primary end point of this study is to assess the cognitive decline, expressed as the loss
      of at least 2 points on the Montreal Cognitive Assessment (MoCA) test 12 months after
      baseline. A comparative analysis of MoCA test values between two groups will be assessed by
      covariate analysis (ANCOVA) introducing in the statistical model these two covariates: arm of
      treatment and MoCA test score at the baseline (based on the exploratory nature of this study
      the significance level on the covariate arm of treatment is 20%).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blind (Participant, Investigator)
measure: Cognitive decline evaluated by the change of MoCA test score compared with Baseline
time frame: 12 months
description: Cognitive decline: expressed as the loss of at least 2 points on Montreal Cognitive Assessment (MoCA) test
measure: Evaluation of selective attention
time frame: 12 months
description: Selective attention assessed by means of Color Word Stroop Test (CWST)
measure: Evaluation of divided attention
time frame: 12 months
description: Divided attention assessed by means of Trail Making Test (TMT)
measure: Evaluation of maintained attention
time frame: 12 months
description: Maintained attention assessed by means of Symbol Digit Modalities Test (SDMT)
measure: Evaluation of memory
time frame: 12 months
description: Memory assessed by means of Rey Auditory-Verbal Learning Test (RAVLT)
measure: Assessment of functional status
time frame: 12 months
description: Functional status measured by Disability Assessment for Dementia scale (DAD)
measure: Evaluation of depressive symptoms
time frame: 12 months
description: Depressive symptoms assessed by means of Center for Epidemiological Studies Depression scale (CES-D)
measure: Assessment of quality of life
time frame: 12 months
description: Quality of life assessed by means of Stroke-Adapted Sickness Impact Profile (SA-SIP30)
measure: Assessment of drugs' safety and tolerability.
time frame: 12 months
description: Evaluation of drugs' side effects incidence between two groups of treatment
arm group label: Choline alphoscerate
arm group type: Experimental
description: Drug: Choline alphoscerate 1200 mg per day and Nimodipine 90 mg per day
concomitant administration
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo and Drug: Nimodipine 90 mg per day only
concomitant administration
intervention type: Drug
intervention name: Choline alphoscerate
description: Choline alphoscerate 600 mg b.i.d plus Nimodipine 30 mg t.i.d
arm group label: Choline alphoscerate
other name: Delecit
intervention type: Drug
intervention name: Placebo
description: Placebo b.i.d plus Nimodipine 30 mg t.i.d
arm group label: Placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
citation: O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST. Vascular cognitive impairment. Lancet Neurol. 2003 Feb;2(2):89-98. doi: 10.1016/s1474-4422(03)00305-3.
PMID: 12849265
citation: Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689-701. doi: 10.1016/S1474-4422(10)70104-6.
PMID: 20610345
citation: Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013 May;12(5):483-97. doi: 10.1016/S1474-4422(13)70060-7. Erratum In: Lancet Neurol. 2013 Jun;12(6):532.
PMID: 23602162
citation: Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.
PMID: 23867200
citation: Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004 Nov 15;226(1-2):67-70. doi: 10.1016/j.jns.2004.09.014.
PMID: 15537523
citation: Smith EE, Cieslak A, Barber P, Chen J, Chen YW, Donnini I, Edwards JD, Frayne R, Field TS, Hegedus J, Hanganu V, Ismail Z, Kanji J, Nakajima M, Noor R, Peca S, Sahlas D, Sharma M, Sposato LA, Swartz RH, Zerna C, Black SE, Hachinski V. Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment. J Am Heart Assoc. 2017 May 5;6(5):e005568. doi: 10.1161/JAHA.117.005568. No abstract available.
PMID: 28476873
citation: Di Perri R, Coppola G, Ambrosio LA, Grasso A, Puca FM, Rizzo M. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res. 1991 Jul-Aug;19(4):330-41. doi: 10.1177/030006059101900406.
PMID: 1916007
citation: Pantoni L, Carosi M, Amigoni S, Mascalchi M, Inzitari D. A preliminary open trial with nimodipine in patients with cognitive impairment and leukoaraiosis. Clin Neuropharmacol. 1996 Dec;19(6):497-506. doi: 10.1097/00002826-199619060-00003.
PMID: 8937788
citation: Pantoni L, del Ser T, Soglian AG, Amigoni S, Spadari G, Binelli D, Inzitari D. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial. Stroke. 2005 Mar;36(3):619-24. doi: 10.1161/01.STR.0000155686.73908.3e. Epub 2005 Feb 3.
PMID: 15692125
citation: Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991.
PMID: 15817019
citation: Poggesi A, Salvadori E, Pantoni L, Pracucci G, Cesari F, Chiti A, Ciolli L, Cosottini M, Del Bene A, De Stefano N, Diciotti S, Dotti MT, Ginestroni A, Giusti B, Gori AM, Nannucci S, Orlandi G, Pescini F, Valenti R, Abbate R, Federico A, Mascalchi M, Murri L, Inzitari D. Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers-The VMCI-Tuscany Study: Rationale, Design, and Methodology. Int J Alzheimers Dis. 2012;2012:608013. doi: 10.1155/2012/608013. Epub 2012 Apr 8.
PMID: 22550606
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero-Universitaria Careggi
investigator full name: Leonardo Pantoni
investigator title: Professor
mesh term: Cognitive Dysfunction
mesh term: Choline
sharing ipd: No