Clinical Trials Register

Summary
EudraCT Number:	2019-001898-87
Sponsor's Protocol Code Number:	STRIVE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

2019-001898-87

A.3

Full title of the trial

Pilot study on sleep pathologies treatments in patients with Vegetative or Minimally conscious state diagnosis for improving Consciounsess level. STRIVE Project.

Studio pilota sui trattamenti delle patologie del sonno in pazienti con una diagnosi di stato vegetativo o di minima coscienza per il miglioramento del livello di coscienza. Progetto STRIVE

A.3.1

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

Pilot study on sleep pathologies treatments in patients with Vegetative or Minimally conscious state

Studio pilota sui trattamenti delle patologie del sonno in pazienti con una diagnosi di stato vegetativo o di minima coscienza

A.3.2

Name or abbreviated title of the trial where available

STRIVE

A.4.1

Sponsor's protocol code number

STRIVE

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	FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA
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	Ministero della Salute
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	Fondazione IRCCS Istituto Neurologico Carlo Besta
B.5.2	Functional name of contact point	Dipartimento di Ricerca e Sviluppo
B.5.3	Address:
B.5.3.1	Street Address	Via Celoria n 11
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	0223942020
B.5.5	Fax number	0223942113
B.5.6	E-mail	crc@istituto-besta.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	NEUPRO - 2 MG/24 H + 4 MG/24 H + 6 MG/24 H+ 8 MG/24 H CEROTTO OTTO TRANSDERMICO 7 CEROTTI + 7 CEROTTI + 7 CEROTTI + 7 CEROTTI TRANDERMICI IN BUSTINA
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB MANUFACTURING IRELAND LTD
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.3.1	Product name	Neupro 2 mg/24 h cerotto transdermico
D.3.2	Product code	[Rotigotina]
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ROTIGOTINA
D.3.9.2	Current sponsor code	92206-54-7
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2 to 4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients diagnosed with vegetative state or minimally conscious state following brain damages without previous either psychiatric or neurological history and with evidence of (i) Obstructive Sleep Apnea syndrome (OSA), (ii) Periodic Limb Movement disorder (PLM), (iii) sleep bruxism (SB).

Pazienti in stato vegetativo e stato di minima coscienza a seguito di grave cerebrolesione acquisita in assenza di malattie neurologiche o psichiatriche in anamnesi e con disturbi del sonno riconducibili a (i) apnee ostruttive nel sonno, (ii) movimenti periodici degli arti inferiori, (iii) Bruxismo.

E.1.1.1

Medical condition in easily understood language

Patients with disorders of consciousness (characterized by a loss of both self and environmental awareness) due to cerebral accident manifesting different sleep pathologies.

I pazienti con disturbi della coscienza (caratterizzati da una perdita di consapevolezza di sè e dell'ambiente) a causa di danni cerebrali acquisiti e manifestanti differenti patologie del sonno.

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	PT
E.1.2	Classification code	10058920
E.1.2	Term	Restless legs syndrome
E.1.2	System Organ Class	10029205 - Nervous system disorders

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	10034715
E.1.2	Term	Persistent vegetative state
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10078293
E.1.2	Term	Obstructive sleep apnea hypopnea syndrome
E.1.2	System Organ Class	100000004855

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 test efficacy of tailored interventions for sleep pathologies in patients with disorders of consciousness through a pilot trial.

Analizzare la tolleranza e l’effetto di interventi mirati per i disturbi del sonno (Apnee ostruttive nel sonno, Movimenti periodici agli arti inferiori e Bruxismo) in pazienti con disordine della coscienza attraverso uno studio pilota esplorativo.

E.2.2

Secondary objectives of the trial

To develop an ICT system combined with cognitive assessment to evaluate patients with disorders of consciousness motor behavioural profile.

To analyze relationship between sleep patterns of patients with disorders of consciousness and their cognitive/consciousness level over time.

Sviluppare un sistema ICT che possa unire i dati ottenuti dalla valutazione clinica con valutazioni quantitative neuro motorie basati sull’elettromiografia e la cinematica.

Analizzare le caratteristiche del sonno dei pazienti con disordine della coscienza con il loro livello di coscienza/comportamento nel tempo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Age greater than 18 years old;
2 ) either Vegetative State or Minimally Conscious State diagnosis;
3 ) time spent in rehabilitation <2 months and time from acute event <3 months;
4) written informal consent obtained from each patients legally authorize representative.

1)Età maggiore di 18 anni;
2) diagnosi di stato vegetativo o stato di minima coscienza a seguito di grave cerebrolesione acquisita (first event);
3) tempo dal ricovero in riabilitazione <2mesi e comunque inferiore a 3 dall’evento acuto;
4) presenza di un rappresentante legale nominato dal tribunale di competenza.

E.4

Principal exclusion criteria

1) Presence in the medical history of major neurological and/or psychiatric disorders before the acute event;
2) presence of severe medical conditions such as kidney failure, liver failure, respiratory failure, presence of continuous epileptiform activity.
3) pregnancy

1)Presenza nella storia clinica di malattie neurologiche o psichiatriche maggiori prima dell’evento acuto;
2) assenza di opercolo osseo a seguito di craniotomia determinante un’ impossibilità di effettuare una corretta valutazione polisonnografica a giudizio del medico neurofisiologo.
3) gravidanza

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients who tollerated the treatment and exploration of the individual difference taking into consideration the following variables:
1) increase of sleep time (computed from 8pm to 8am of the day after);
2) reduction of the ratio between diurnal sleep (from 8am to 8pm) and night sleep (from 8pm to 8am) without a reduction of the total amount of sleep time within a day (considering the 24 hours);
3) number of circadian cycles;
4) obstructive sleep apnea syndrome and periodic limb movement disorder’ indexes.

Percentuale di pazienti che ha tollerato il trattamento e rilevazione delle differenze individuali nelle seguenti variabili:
1) aumento del tempo totale di sonno notturno (calcolato dalle ore 20:00 alle ore 8:00 del giorno successivo);
2) riduzione del rapporto tra sonno diurno (ore 8:00/20:00)/sonno notturno (ore 20:00-8:00 del giorno successivo) senza decremento del tempo totale di sonno nelle 24 h;
3) numero di cicli sonno/veglia;
4) Indici legati alle apnee ostruttive nel sonno e ai movimenti periodici degli arti inferiori.

E.5.1.1

Timepoint(s) of evaluation of this end point

20 months

20 mesi

E.5.2

Secondary end point(s)

Correlation between sleep variables (total amount of sleep time, REM and NREM duration, number of sleep cycles in each patient) and both the clinical and behavioural indexes (CRS-r, data recorded by the ICT system).; ICT system testing by means of a questionnaire measuring (i) device capacity in selecting the muscles to be considered for clinical evaluation; (ii) device ability in recording the information for the established time; (iii) wearable device optimization on the patients; (iv) device usability. It is required a positive judgment from at least the 75% of the clinical staff.

Correlazione tra i cambiamenti delle variabili relative al sonno (tempo totale di sonno, durata della fase REM e NREM, numero di fasi del sonno presenti in un paziente) e gli indici di performance clinica e comportamentale legate ai livelli di coscienza (CRS-r, dati derivanti dal sistema ICT).; Test di prova del sistema ICT valutato attraverso un questionario che misura: (i) capacità di utilizzare lo strumento per selezionare i muscoli da utilizzare per la valutazione clinica; (ii) capacità del sistema di registrare le informazioni per il tempo prestabilito; (iii) ottimizzazione dell’applicazione del fissaggio dei device wearable sul paziente; (iv) fruibilità di utilizzo. Il test si considererà superato se otterrà un giudizio positivo da parte di almeno il 75% degli operatori coinvolti nell’assessment in tutti e quattro gli items.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 months; 9 months

30 mesi; 9 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

E.6.4

Safety

Yes

E.6.5

Efficacy

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

nessun trattamento

no treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

PATIENTS WITH DISORDERS OF CONSCIOUSNESS FOLLOWING SEVERE ACQUIRED BRAIN INJURIES

PAZIENTI CON DISORDINE DELLA COSCIENZA A SEGUITO DI GRAVE CEREBROLESIONE ACQUISITA

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 BE FOLLOWED ACCORDING TO NORMAL CLINICAL PRACTICE

I PAZIENTI SARANNO SEGUITI SECONDO NORMALE PRATICA CLINICA

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

2019-09-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-12

P. End of Trial
P.	End of Trial Status	Ongoing

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