Propranolol for familial cerebral cavernous malformation (Treat_CCM): study protocol for a randomized controlled pilot trial.
Adrenergic beta-Antagonists
/ administration & dosage
Adult
Animals
Anxiety
/ epidemiology
Case-Control Studies
Depression
/ epidemiology
Disease Progression
Female
Hemangioma, Cavernous, Central Nervous System
/ diagnostic imaging
Humans
Intracranial Hemorrhages
/ epidemiology
Italy
/ epidemiology
Magnetic Resonance Imaging
/ methods
Male
Mice
Models, Animal
Nervous System Diseases
/ epidemiology
Propranolol
/ administration & dosage
Prospective Studies
Quality of Life
Safety
Severity of Illness Index
Treatment Outcome
Cerebral cavernous malformation
Magnetic resonance imaging
Propranolol
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
12 May 2020
12 May 2020
Historique:
received:
04
07
2019
accepted:
24
02
2020
entrez:
14
5
2020
pubmed:
14
5
2020
medline:
27
1
2021
Statut:
epublish
Résumé
Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40-80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.
Sections du résumé
BACKGROUND
BACKGROUND
Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression.
METHODS
METHODS
Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40-80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory).
DISCUSSION
CONCLUSIONS
Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrails.gov, NCT03589014. Retrospectively registered on 17 July 2018.
Identifiants
pubmed: 32398113
doi: 10.1186/s13063-020-4202-x
pii: 10.1186/s13063-020-4202-x
pmc: PMC7218540
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Propranolol
9Y8NXQ24VQ
Banques de données
ClinicalTrials.gov
['NCT03589014']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
401Subventions
Organisme : Chief Scientist Office
ID : CZG/2/265
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1002605
Pays : United Kingdom
Organisme : Medical Research Council
ID : G108/613
Pays : United Kingdom
Organisme : Agenzia Italiana del Farmaco (AIFA)
ID : AIFA-2016-02364593
Investigateurs
R Pallini
(R)
G d'Alessandris
(G)
F Pignotti
(F)
C Sturiale
(C)
A Albanese
(A)
S Lanfranconi
(S)
E Scola
(E)
G A Bertani
(GA)
B Zarino
(B)
G Valcamonica
(G)
D Ronchi
(D)
M R Carriero
(MR)
E Scelzo
(E)
G Faragò
(G)
S Pogliani
(S)
U de Grazia
(U)
C Bossi
(C)
E Mazzon
(E)
S Marino
(S)
R Ciurleo
(R)
C Fusco
(C)
A Petracca
(A)
L D'Agruma
(L)
P Raggi
(P)
A Simeone
(A)
P d'Orio
(P)
M G Lampugnani
(MG)
E Dejana
(E)
E B Nicolis
(EB)
A Vasamì
(A)
D Novelli
(D)
V Torri
(V)
J M T A Meessen
(JMTA)
R Latini
(R)
G Balconi
(G)
A Foresta
(A)
M G Buratti
(MG)
M Carrara
(M)
M L Ojeda Fernandez
(MLO)
R Al-Shahi Salman
(RA)
R Treglia
(R)
A P Maggioni
(AP)
E Beghi
(E)
M Tettamanti
(M)
C Regna-Gladin
(C)
A Prelle
(A)
M Mangiavacchi
(M)
Marco Poloni
(M)
F Lazzaroni
(F)
M Malinverno
(M)
D Novelli
(D)
E B Nicolis
(EB)
M G Buratti
(MG)
A Vasami
(A)
C Ungaro
(C)
F Raucci
(F)
M Castori
(M)
L Tassi
(L)
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