Choline Alphoscerate-Nimodipine in Vascular Cognitive Impairment (CONIVAD)

January 9, 2020 updated by: Leonardo Pantoni, Azienda Ospedaliero-Universitaria Careggi

Pilot Study on the Association Choline Alphoscerate-Nimodipine in Patients With Subcortical Vascular Cognitive Impairment

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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%).

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Firenze, Italy, 50134
        • Stroke Unit, VAS-COG clinic, Azienda Ospedaliero Universitaria Careggi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Cognitive impairment from 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.

Exclusion Criteria:

  1. Absence of objectionable cognitive impairment or presence of dementia of severe degree defined by CDR score > 2.0.
  2. Unavailability of brain MRI (in case of absolute contraindications, the use of cranial CT is allowed).
  3. Expected poor compliance with the study protocol.
  4. Past diagnosis of major depression, schizophrenia, major anxiety syndrome, or manic- depressive illness.
  5. Diagnosis of degenerative cognitive impairment based on clinical and/or neuroradiological findings (i.e., patients with prevailing memory impairment, or with medial temporal atrophy on brain MRI in absence of evident vascular abnormalities; i.e., Alzheimer disease as defined using the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, Parkinson disease, Huntington disease, frontotemporal dementia).
  6. Diagnosis of cognitive impairment from other causes (i.e., vitamine B12 and folic acid deficiency, thyroid disorders, metabolic diseases, head trauma, tumor or infections of the central nervous system, normal pressure hydrocephalus).
  7. Medical conditions expected to progress, recur, or change to such a degree to interfere with the assessment of the clinical and mental status.
  8. Clinically relevant cardiac or pulmonary insufficiency.
  9. Relevant electrocardiograph abnormalities; bradycardia (50 bpm) or tachycardia (120 bpm) under resting conditions.
  10. Myocardial infarction within the past 6 months.
  11. Stroke still requiring neurological rehabilitation.
  12. Severe/untreated blood pressure (systolic 180 mm Hg, diastolic 95 mm Hg).
  13. Clinically relevant liver function impairment.
  14. Insulin-dependent diabetes mellitus.
  15. Idiopathic epilepsy and anti-epileptic treatment.
  16. Severe anemia (Hb <10 mg/dL).
  17. Severe gastrointestinal disease.
  18. Cancer.
  19. Known intolerance to study drugs.
  20. Coexistent serious illnesses that would imply a drop-out before the end of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Choline alphoscerate

Drug: Choline alphoscerate 1200 mg per day and Nimodipine 90 mg per day

concomitant administration
Drug: Choline alphoscerate
Choline alphoscerate 600 mg b.i.d plus Nimodipine 30 mg t.i.d
Other Names:
  • Delecit
Placebo Comparator: Placebo

Placebo and Drug: Nimodipine 90 mg per day only

concomitant administration
Drug: Placebo
Placebo b.i.d plus Nimodipine 30 mg t.i.d

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive decline evaluated by the change of MoCA test score compared with Baseline
Time Frame: 12 months
Cognitive decline: expressed as the loss of at least 2 points on Montreal Cognitive Assessment (MoCA) test
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of selective attention
Time Frame: 12 months
Selective attention assessed by means of Color Word Stroop Test (CWST)
12 months
Evaluation of divided attention
Time Frame: 12 months
Divided attention assessed by means of Trail Making Test (TMT)
12 months
Evaluation of maintained attention
Time Frame: 12 months
Maintained attention assessed by means of Symbol Digit Modalities Test (SDMT)
12 months
Evaluation of memory
Time Frame: 12 months
Memory assessed by means of Rey Auditory-Verbal Learning Test (RAVLT)
12 months
Assessment of functional status
Time Frame: 12 months
Functional status measured by Disability Assessment for Dementia scale (DAD)
12 months
Evaluation of depressive symptoms
Time Frame: 12 months
Depressive symptoms assessed by means of Center for Epidemiological Studies Depression scale (CES-D)
12 months
Assessment of quality of life
Time Frame: 12 months
Quality of life assessed by means of Stroke-Adapted Sickness Impact Profile (SA-SIP30)
12 months
Assessment of drugs' safety and tolerability.
Time Frame: 12 months
Evaluation of drugs' side effects incidence between two groups of treatment
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero-Universitaria Careggi

Collaborators

MDM S.p.A.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2017

Primary Completion (Actual)

July 9, 2019

Study Completion (Actual)

July 9, 2019

Study Registration Dates

First Submitted

July 19, 2017

First Submitted That Met QC Criteria

July 21, 2017

First Posted (Actual)

July 25, 2017

Study Record Updates

Last Update Posted (Actual)

January 13, 2020

Last Update Submitted That Met QC Criteria

January 9, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-003188-13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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