CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), is a rare autosomal dominant disorder characterized by recurrent strokes starting in mid-adulthood and leading in some to severe motor disability with pseudobulbar palsy and dementia of the subcortical type MedDRA version: 9.1 Level: HLGT Classification code 10008804 Term: Chromosomal abnormalities and abnormal gene carriers
Conditions
Interventions
Product Name: Phenoptin
Product Code: 6R-BH4
Pharmaceutical Form: Oral powder
INN or Proposed INN: sapropterin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Sponsors
AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA (A.O. DI RILIEVO NAZIONALE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age > 30 and ≤ 65 years - Diagnosis of CADASIL confirmed by the identification of a mutation in the Notch3 gene - Informed consent Are the trial subjects under 18? no Number of subjects for this age range: 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Dementia (DSM-IV criteria) with a SIDAM score 180 mmHg systolic and /or 110 mmHg diastolic). - Hypotension at Screening, defined as seated resting BP values of 2.5 mg/dL or hepatic enzymes >2X normal - Pacemakers, implantable cardioverter defibrillators or metallic implants not compatible with MRI scanning - Concomitant treatment with methotrexate, levodopa, phosphodiesterase-3 (milrinone) or phosphodiesterase -5 inhibitors (sildenafil, taladafil, vardenafil) , pentoxyfylline, nitrate/nitrite-based vasodilators, L-arginine, or dietary supplements containing L-arginine or gingko biloba within 30 days prior to Screening, or anticipated need for treatment with any of these agents during the course of the study. - Participation in other drug trials within the last 30 days before start for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study objective is to determine whether chronic administration of 6R-BH4 for 24 months to CADASIL patients results in improved endothelial function, as assessed by FMD, when compared to placebo.;Secondary Objective: Secondary study objectives are to determine differences between the two treatment arms in terms of tolerability, occurrence of new strokes or deaths, and progression of disability, as assessed by specific scales: Barthel index, Rankin scale, NIHSS;Primary end point(s): Change in endothelial function by FMD assessment after 24-month treatment with 6R-BH4 or placebo | — |
Countries
Italy
Outcome results
None listed