Treat_CCM: Propranolol in Cerebral Cavernous Malformation (Treat_CCM)
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|ClinicalTrials.gov Identifier: NCT03589014|
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : January 10, 2019
Cerebral Cavernous Malformation (CCM) is a cerebrovascular disease which can be either congenital in origin or sporadic and is characterized by the presence of isolated or multiple CCM lesions, causing recurrent headache, seizures, focal neurological deficits and hemorrhages. Inasmuch, to date, the only curative treatment available is limited to surgical lesion eradication or stereotactic radiosurgery. It is therefore necessary to find an effective medical treatment that may limit disease progression and decrease the burden of adverse clinical events. The non-selective betablocker propranolol has been found to be effective in the treatment of infantile cutaneous hemangioma, and anecdotal reports have been published on its efficacy in CCM. The safety profile of propranolol has been documented in millions of patients of all ages.
The primary objective of this exploratory trial is to test whether a chronic treatment with propranolol will reduce the burden of cerebrovascular lesions, of clinical events and symptoms in patients with familial CCM.
|Condition or disease||Intervention/treatment||Phase|
|Cerebral Cavernous Malformation||Drug: Propranolol||Phase 2|
The project will consist of a multicenter, open-label, randomized study (PROBE design) in patients with CCM to be randomized in a 2:1 ratio (propranolol:control) and will allow comparison of 2 groups: one receiving propranolol (recommended initial dose is 40 mg bid, to be uptitrated to 80 mg bid) on the top of recommended standard care, the other receiving recommended standard care. This investigator-driven study will be open-label with a PROBE design will be applied so that each MRI exam will be centrally read and all adverse clinical events will be centrally adjudicated. It should be pointed out that by no means surgery, whenever indicated, will be delayed and/or avoided because of study treatment allocation.
The purpose of this exploratory trial is to test whether a chronic treatment with propranolol will reduce the burden of cerebrovascular lesions, of clinical events and symptoms in patients with familial CCM. Inherited CCM is a rare disease with a prevalence of less than 5/10.000. Thus, since the number of patients to be included in this exploratory trial will be insufficient to prove or disprove a statistically significant beneficial effect of propranolol on clinical events, the extension to more centers and patients is formally included in the present protocol. Special care will be paid to the biologic consistency of the different endpoints, even if none of them will yield statistically significant differences. The assessment of the tolerability of propranolol in normotensive otherwise healthy patients is another clinically relevant endpoint
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
Treat_CCM is a Prospective Randomized Open Trial with Blinded Evaluation of outcomes (PROBE).
Clinical events CCM-related (i.e. intra-cerebral hemorrhage and focal neurological deficits including seizures) will be blindly adjudicated by an independent Event Committee.All MRI exams will be read in a Central Laboratory by experienced neuroradiologists, unaware of patient identification and study treatment.
|Official Title:||Treat_CCM Clinical Trial A Multicenter Randomized Clinical Trial on Propranolol in Cerebral Cavernous Malformation|
|Actual Study Start Date :||March 1, 2018|
|Estimated Primary Completion Date :||July 31, 2020|
|Estimated Study Completion Date :||October 31, 2020|
No Intervention: Control
Standard Treatments recommended for CCM
Initial oral dose 40 mg bid, uptitrated to 80mg bid
Patients randomized to the experimental arm will receive propranolol on top of standard recommended treatment for CCM. Initial oral dose of 40 mg bid will be uptitrated to 80 mg bid in the absence of excessive bradycardia or hypotension.
Other Name: Inderal
- Adverse clinical events CCM-related. [ Time Frame: up to 24 months ]New occurrence of clinical events CCM-related, that is intra-cerebral hemorrhage (ICH) and focal neurological deficits (FND) including seizures.
- De novo CCM lesions depiction on MRI. [ Time Frame: up to 24 months ]De novo CCM lesions depiction will be obtained on MRI QSM and Susceptibility Weighted Images (SWI) that is very sensitive to hemoglobin and iron deposition.
- Adverse clinical outcomes, other than ICH and FND. [ Time Frame: up to 24 months ]Global disability and health related quality of life as assessed by Beck Depression Inventory -BDI- questionnaire. BDI is made of 21 questions scored on a scale from 0 to 3, 0 representing the best condition. Final score will be the sum of all scores and will range from 0 to 63, were 0 is the best condition.
- Adverse clinical outcomes, other than ICH and FND. [ Time Frame: up to 24 months ]Global disability and health related quality of life as assessed by SF-36 questionnaire. SF-36 is made of 36 questions scored on a scale from 0 to 100 representing the highest level of functioning possible. Questions are aggregated in 8 dimensions of health (eg pain, phsical functioning etc.).
- Location and MRI signal characteristics of CCM lesions at MRI. [ Time Frame: up to 24 months ]Location and MRI signal characteristics of CCM lesions will be assessed by 3 T brain MRI. The encephalic regions evaluated will be: cerebellum, brainstem, right/left hemisphere, right/left basal ganglia. Lesions with previous surgical treatment will be excluded from imaging analysis
- Diameter of CCM lesions at MRI. [ Time Frame: up to 24 months ]Diameter will be assessed in millimeters.
- Length of CCM lesions at MRI [ Time Frame: up to 24 months ]Length will be assessed in millimeters.
- Micro-hemorrhages at MRI. [ Time Frame: up to 24 months ]Micro-hemorrhages will be assessed by magnetic susceptibility of the brain tissue, a biophysical property proportional to local iron content (quantitative susceptibility mapping, QSM). Unit of Measure of QSM is parts per million (ppm). Changes from baseline will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03589014
|Contact: Roberto Latini, MDfirstname.lastname@example.org|
|Contact: Silvia Lanfranconi, MDemail@example.com|
|IRCCS Casa Sollievo della Sofferenza||Not yet recruiting|
|San Giovanni Rotondo, FG, Italy, 71013|
|Contact: Marco Castori 0882416288 firstname.lastname@example.org|
|IRCCS Centro Neurolesi "Bonino Pulejo"||Recruiting|
|Messina, ME, Italy, 98124|
|Contact: Emanuela Mazzon +3909060128172 email@example.com|
|Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico||Recruiting|
|Milano, Mi, Italy, 20122|
|Contact: Silvia Lanfranconi +390255033870 firstname.lastname@example.org|
|Fond. IRCCS Ist. Naz. Neurologico Carlo Besta||Recruiting|
|Milano, MI, Italy, 20133|
|Contact: Maria Rita Carriero +390223943310 email@example.com|
|ASST Grande Ospedale Metropolitano Niguarda||Recruiting|
|Milano, MI, Italy, 20162|
|Contact: Laura Tassi +390264442874 firstname.lastname@example.org|
|Fondazione Policlinico Universitario "A. Gemelli"||Recruiting|
|Roma, RM, Italy, 00168|
|Contact: Roberto Pallini +39063015343 Roberto.Pallini@unicatt.it|
|Study Chair:||Elisabetta Dejana, Professor||IFOM, The FIRC Institute of Molecular Oncology|
|Study Director:||Roberto Latini||Istituto Di Ricerche Farmacologiche Mario Negri|