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2 results on '"CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA )"'

1. Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

Author

Frédéric Dutheil, Yves Boirie, Ana Marques, Elodie Durand, Maria Livia Fantini, Franck Durif, Isabelle Rieu, Aurélien Mulliez, Groupe de sociologie politique et morale (GSPM), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne (LAPSCO), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), École d’Orthoptie - Clermont-Ferrand (EO - UdA), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Groupe de sociologie politique et morale ( GSPM ), École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne ( LAPSCO ), Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), École d’Orthoptie - Clermont-Ferrand ( EO - UdA ), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I ( UdA ), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Unité de Nutrition Humaine ( UNH ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, Blood Glucose, Male, Parkinson's disease, Dopamine, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Administration, Oral, Neurodegenerative disease, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, Insulin, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Diabetes, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, 3. Good health, Neurology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, medicine.symptom, medicine.drug, medicine.medical_specialty, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Aged, Glucose Metabolism Disorders, Retrospective Studies, Autonomous nervous system, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Dysautonomia, Metabolism, Glucose Tolerance Test, medicine.disease, 030104 developmental biology, Endocrinology, Autonomic Nervous System Diseases, Blood sugar regulation, Neurology (clinical), Geriatrics and Gerontology, business, Body mass index, 030217 neurology & neurosurgery
Abstract

Objective To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. Methods Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). Results Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l-1; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p Conclusion Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia.

Published
2018

2. Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial

Author

Dutheil, Frédéric, Durand, Élodie, Rieu, Isabelle, Mulliez, Aurélien, Fantini, Maria Livia, Boirie, Yves, Fernagut, Pierre-Olivier, Azulay, J.P., Vidailhet, M., Tranchant, C., Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilios, Azulay, Jean-Philippe, Haddad, Raphaël, Guimarães-Costa, Raquel, Mariani, Louise-Laure, Cormier-Dequaire, Florence, Thalamas, Claire, Galitzky, Monique, Boraud, Thomas, Debilly, Bérengère, Eusebio, Alexandre, Houot, Marion, Dellapina, Estelle, Chaigneau, Véronique, Salis, Alexandrine, Lacomblez, Lucette, Benel, Laurent, Rascol, Olivier, Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Plateforme F-CRIN, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Avignon Université (AU), École d’Orthoptie - Clermont-Ferrand (EO - UdA), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut National de la Recherche Agronomique (INRA), CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, CIC Pitié Neurosciences, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), Physiologie et physiopathologie de la signalisation cellulaire (PPSC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CIC - Biotherapie - Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Toulouse, Fédération des Maladies du Système Nerveux, Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, Dyskinesia, Drug-Induced, Parkinson's disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Dopamine Agents, law.invention, Antiparkinson Agents, Levodopa, 0302 clinical medicine, Randomized controlled trial, law, Medicine, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Cross-Over Studies, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, 3. Good health, Clinical trial, Treatment Outcome, Neurology, Female, medicine.symptom, Naftazone, medicine.drug, medicine.medical_specialty, Population, Placebo, 03 medical and health sciences, Double-Blind Method, Internal medicine, Humans, education, Aged, Levodopa-induced dyskinesia, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, 030104 developmental biology, Dyskinesia, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Naphthoquinones
Abstract

International audience; Introduction: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study.Methods: We conducted a double-blind randomized placebo-controlled cross-over trial in PD patients with motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for 14 days. The two co-primary endpoints were the area under curve (AUC) of motor (MDS-UPDRS part III) and dyskinesia (AIMS) scores during an acute levodopa challenge performed at the end of each period. Secondary endpoints were UDysRS and axial symptoms scores during the challenge; AIMS, UDysRS, and time spent with or without dyskinesia the day before the challenge. The primary analysis was performed in the per protocol population.Results: Sixteen patients were included in the analysis. There was no difference between naftazone and placebo for the AUC of MDS-UPDRS III (-89, 95%CI[-1071; 893], p = 0.85), and AIMS (70, 95%CI[-192; 332], p = 0.57). At the end of treatment periods, AIMS score tended to be lower with naftazone than placebo (4.4 ± 3.4 versus 6.7 ± 4.4, p = 0.07), but UDysRS scores and other secondary outcomes were not different. Naftazone was safe and well tolerated.Conclusions: This study did not confirm previous results on the efficacy of naftazone on dyskinesia nor motor fluctuations highlighting the problem of translating results obtained in preclinical models into clinical trials. Further investigation of naftazone may be conducted in PD with longer treatment duration.

Published
2018

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