Dynamic Neuroimaging Biomarkers in Huntington's Disease
Dynamic Neuroimaging Biomarkers in Huntington's Disease
NCT ID: NCT02639871 Phase: Status: COMPLETED Enrollment: 81 Completion: 2019-06-24
Conditions
Brain Neuroimaging Biomarkers in Huntington Disease
Summary
There is no curative treatment available today in Huntington disease (HD) despite the identification of the mutated gene 20 years ago. Nonetheless, safe and promising therapeutic strategies targeting brain energy metabolism are now becoming available.
In view of the small effect sizes of any clinical parameter in HD, robust neuroimaging biomarkers reflecting brain energy metabolism are therefore urgently needed to better assess the potential of therapeutics targeting the mitochondria, and especially the Krebs cycle. Identifying such biomarkers at the presymptomatic phase in HD also provides a unique window for therapeutic intervention, which can be used as a proof-of-concept for the real challenge of tomorrow's medicine: the prevention of neurodegeneration HDeNERGY is an observational study consisting of the transfer of methods from preclinical to clinical studies and their application in HD. HDeNERGY aim at optimizing MRI/MRS methods to study the dynamics of brain energy metabolism. At the CENIR (Centre de neuro-imagerie et de recherche, Paris) the determination of creatine kinase rate will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20) together with the methods previously validated in HD patients (Mochel et al., 2012b) to determine the ratio of inorganic phosphate (Pi)/ phosphocreatine (PCr) during visual stimulation in presymptomatic individuals. The Chemical Exchange Saturation Transfer (CEST) method on the 3T clinical scanner of CENIR will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20).
The cerebral synthesis rate of creatine phosphate and of brain glutamate concentrations and pH values will be compared between controls, HD patients and HD presymptomatic individuals, and correlated with clinical pa
Primary Outcome
Cerebral synthesis rate of creatine phosphate