Corticobasal syndrome (CBS) is a rapidly progressive neurodegenerative disorder with an average survival time of about 6-8 years after the first clinical manifestation. No potent symptomatic treatment is currently available. A disease-modifying therapy does not exist either. Neuroinflammation is key to the pathogenesis in neurodegenerative diseases with Tau- and/or AD-pathology. There is strong evidence that phenylbutyrate can modulate microglial function by enhancing their phagocytic activity, most likely by epigenetic mechanisms. So the main goal of this clinical trial is to study a potential disease-modifying effect of treatment with glycerol phenylbutyrate (GPB), which is a prodrug of phenylbutyric acid, for 26 weeks assessed by the levels of the biomarker neurofilament light chain (NfL) indicating disease progression in CBS. Given the aggressive nature of CBS, it is feasible to study effects of GPB on plasma NfL levels.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
Duration of Treatment: 26 weeks, twice daily Dosage: * weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo) * weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)
Duration of Treatment: 26 weeks, twice daily Dosage: * weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo) * weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)
Klinikum der Universität München (KUM), Campus Großhadern, Klinik und Poliklinik für Neurologie & German Center for Neurodegenerative Diseases (DZNE), Department of Neurology
Munich, Bavaria, Germany
RECRUITINGKlinikum rechts der Isar Technische Universität München Klinik und Poliklinik für Neurologie & German Center for Neurodegenerative Diseases (DZNE), Department of Neurology
Munich, Bavaria, Germany
RECRUITINGTo assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glycerol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with
To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glyc-erol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with CBS.
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III), min value 0- max value 132 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: Progressive Supranuclear Palsy Rating Scale (PSP-RS), min value 0- max value 100 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale:Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS), min value 0- max value 21 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: Cortical Basal ganglia Functional Scale (CBFS), min value 0- max value 124 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: Dementia Apraxia Test (DATE), min value 0 (worse outcome) - max value 60
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: MONTREAL COGNITIVE ASSESSMENT (MoCA), min value 0 (worse outcome) - max value 30
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: SCHWAB AND ENGLAND ACTIVITIES OF DAILY LIVING SCALE (SEADL), min value 0 (worse outcome) - max value 100%
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: Clinical Global Impression (CGI-s), min value 1- max value 7 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
To assess longitudinal changes in clinical scales
To assess longitudinal changes in clinical scale: PSP RATING SCALE (PSP-QoL), min value 0- max value 180 (worse outcome)
Time frame: 26 weeks (between V1 and V3)
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