Clinical Trials Register

Summary
EudraCT Number:	2015-003188-13
Sponsor's Protocol Code Number:	CONIVAD
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-02-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-003188-13

A.3

Full title of the trial

Pilot study on the association choline alphoscerate-nimodipine in patients with subcortical vascular cognitive impairment

Studio pilota sulla associazione colina alfoscerato-nimodipina in pazienti affetti da deterioramento cognitivo vascolare su base microangiopatica

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Choline alphoscerate-nimodipine in vascular cognitive impairment

Colina alfoscerato-nimodipina nel deterioramento cognitivo vascolare

A.3.2

Name or abbreviated title of the trial where available

CONIVAD

A.4.1

Sponsor's protocol code number

CONIVAD

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZIENDA OSPEDALIERO-UNIVERSITARIA CAREGGI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MDM S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AZIENDA OSPEDALIERO-UNIVERSITARIA CAREGGI
B.5.2	Functional name of contact point	SOD Stroke Unit
B.5.3	Address:
B.5.3.1	Street Address	Largo Brambilla 3
B.5.3.2	Town/ city	Firenze
B.5.3.3	Post code	50134
B.5.3.4	Country	Italy
B.5.4	Telephone number	055 7947665
B.5.5	Fax number	055 7946018
B.5.6	E-mail	francesca.pescini@unifi.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	DELECIT - 600 mg soluzione orale
D.2.1.1.2	Name of the Marketing Authorisation holder	MDM S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLINA ALFOSCERATO
D.3.9.2	Current sponsor code	COLINA ALFOSCERATO
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ISKIDROP - 30 MG/0. 75 ML GOCCE ORALI, SOLUZIONE FLACONE DA 25 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	MDM S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIMODIPINA
D.3.9.2	Current sponsor code	NIMODIPINA
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subcortical vascular cognitive impairment

Deterioramento cognitivo vascolare su base microangiopatica

E.1.1.1

Medical condition in easily understood language

Cognitive decline

Declino cognitivo

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10009843
E.1.2	Term	Cognitive deterioration
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

Valutare se l¿associazione di colina alfoscerato 1200 mg/die e nimodipina 90 mg/die somministrati per os sia pi¿ efficace della associazione nimodipina-placebo nel ridurre il declino cognitivo in pazienti con deterioramento cognitivo su base microvascolare

E.2.2

Secondary objectives of the trial

1) To investigate the effects of treatments on the functional status, mood, and quality of life.
2) To investigate the effects of treatments on cognitive performances at second level neuropsychological tests.
3) To investigate the tolerability of the combination of choline alphoscerate 1200mg per day and nimodipine 90mg per day in patients with subcortical vascular cognitive impairment.
4) To evaluate the incidence of adverse events in both treated groups.

1) Valutare gli effetti dei trattamenti su stato funzionale, tono dell¿umore, e qualit¿ della vita.
2) Valutare gli effetti dei trattamenti sulla prestazione cognitiva ai test neuropsicologici di secondo livello.
3) Valutare la tollerabilit¿ dell¿associazione colina alfoscerato 1200 mg/die - nimodipina 90 mg in pazienti con deterioramento cognitivo su base microvascolare.
4) Valutare l¿incidenza di eventi avversi nei 2 gruppi di trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

1) Deterioramento cognitivo di grado lieve o moderato definito con punteggio Clinical Deterioration Rating (CDR) compreso fra 0.5 e 2.0.
2) Evidenza alla RM encefalo di patologia di tipo microvascolare sottocorticale (leucoaraiosi di grado moderato o grave secondo la scala visiva di Fazekas modificata e/o presenza di infarti lacunari). 3) Consenso alla partecipazione allo studio

E.4

Principal exclusion criteria

1) Absence of objectivizable 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 NINCDS/ADRDA 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.

1) Assenza di deterioramento cognitivo obbiettivabile o demenza di grado avanzato definita come CDR >2.0.
2) Indisponibilità di RM encefalo (in caso di controindicazioni assolute è consentito l'uso di TC cranio).
3) Prevista scarsa compliance al protocollo di studio.
4) Pregressa diagnosi di depressione maggiore, schizofrenia, disturbo d'ansia, o sindrome maniaco-depressiva.
5) Diagnosi di deterioramento cognitivo su base degenerativa su base clinica e/o neuroimaging (es. quadri a prevalente compromissione della memoria, pazienti con quadro RMN di grave atrofia temporo-mesiale in assenza di evidenti alterazioni vascolari; es. malattia di Alzheimer secondo i criteri NINCDS/ADRDA, malattia di Parkinson, malattia di Huntington, demenza fronto-temporale).
6) Diagnosi di deterioramento cognitivo da altre cause (es. deficit vit. B12 e folati, distiroidismi, malattie metaboliche, traumi cranici, neoplasie o infezioni del sistema nervoso centrale, idrocefalo normoteso, ecc.).
7) Condizioni mediche di cui sia attesa una progressione, o una ricorrenza, o un cambiamento di grado tale da interferire con la valutazione dello stato clinico e mentale dei pazienti.
8) Scompenso cardiaco o insufficienza respiratoria clinicamente rilevanti.
9) Rilevanti anomalie ECG, bradicardia (< 50 bpm) o tachicardia (> 120 bpm) in condizioni di riposo.
10) Infarto miocardico acuto nei precedenti 6 mesi.
11) Ictus ancora necessitante di riabilitazione neurologica.
12) Ipertensione arteriosa severa/non trattata (sistolica > 180 mmHg, diastolica >95 mmHg).
13) Disfunzione epatica clinicamente rilevante.
14) Diabete mellito insulino-dipendente.
15) Epilessia idiopatica e trattamento anti-epilettico.
16) Anemia grave (emoglobina <10 mg/dL).
17) Malattie gastro-intestinali gravi.
18) Malattie tumorali.
19) Nota intolleranza ai farmaci in studio.
20) Gravi co-patologie che facciano prevedere un drop-out prima del termine del trial.

E.5 End points

E.5.1

Primary end point(s)

Cognitive decline: expressed as the loss of at least 2 points on Montreal Cognitive Assessment (MoCA) test.

Declino cognitivo: espresso in termini di perdita di almeno due punti al test Montreal Cognitive Assessment (MoCA).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

Neuropsychological tests for the assessment of attention and executive functions. Assessment of functional status (DAD scale), mood (CES-D scale), quality of life (Stroke-Adapted SIP30). Assessment of drugs' safety and tolerability.

Test neuropsicologici finalizzati a valutare i domini cognitivi relativi ad attenzione e funzioni esecutive. Scala funzionale DAD. Scala per depressione CES-D. Scala per qualit¿ della vita (Stroke-Adapted SIP30). Sicurezza e tollerabilit¿ dei farmaci.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

patients will undergo usual standard follow-up visits

i pazienti seguiranno la prassi clinica di controllo ambulatoriale

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-30

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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