LMU Klinikum — Biomedical Watch V2

Traitements6programmes

Essais3liés

Publications4liées

SourceDBlocale

Traitements

6

Molécule	Indication / population	Phase	Objectif	Pays	Résultat
clemastine (8 mg/day)Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Cognitive deficits occur as early as the prodromal phase of the illness and significantly determine its outcome. Pathophysiologically, SZ is regarded as a disconnectome disorder in which frontal and temporal brain regions are functionally disconnected, which contributes substantially to the development of cognitive dysfunction. Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, the study will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes.	SEP	Phase 2	Remyélinisation		À vérifier
GENOMIT — Global Registry and Natural History Study for Mitochondrial DisordersThe main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.	Épilepsie, Myopathies	À vérifier	Remyélinisation indirecte / réparation	Austria, Germany, Italy	À vérifier
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular DisordersThe primary aim is to characterize the prevalence, severity and quality of musculoskeletal nociceptive pain in adult patients with neuromuscular disorders (NMD). The secondary objectives are to evaluate whether severity and distribution of muscle pain is associated with muscle function, and to assess whether muscle pain is associated with alterations of muscle elasticity and muscle stiffness. Results of patients with neuromuscular disorders will be compared to age- and gender-matched healthy volunteers. Approx. 70 patients with neuromuscular disorders and 20 healthy volunteers will be enrolled, including patients with the following neuromuscular disorders: histologically confirmed inclusion body myositis (IBM), genetically confirmed late-onset Pompe disease (LOPD), genetically confirmed spinal muscular atrophy type 3 (SMA3), genetically confirmed facio-scapulo-humeral muscle dystrophy (FSHD), genetically confirmed myotonic dystrophy type 1 or type 2 (DM1, DM2). The duration of patient recruitment will be around 12 months.	Myopathies	À vérifier	Traitement symptomatique	Germany	À vérifier
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular DisordersThe primary aim is to characterize the prevalence, severity and quality of musculoskeletal nociceptive pain in adult patients with neuromuscular disorders (NMD). The secondary objectives are to evaluate whether severity and distribution of muscle pain is associated with muscle function, and to assess whether muscle pain is associated with alterations of muscle elasticity and muscle stiffness. Results of patients with neuromuscular disorders will be compared to age- and gender-matched healthy volunteers. Approx. 70 patients with neuromuscular disorders and 20 healthy volunteers will be enrolled, including patients with the following neuromuscular disorders: histologically confirmed inclusion body myositis (IBM), genetically confirmed late-onset Pompe disease (LOPD), genetically confirmed spinal muscular atrophy type 3 (SMA3), genetically confirmed facio-scapulo-humeral muscle dystrophy (FSHD), genetically confirmed myotonic dystrophy type 1 or type 2 (DM1, DM2). The duration of patient recruitment will be around 12 months.	Myopathies	À vérifier	Traitement symptomatique	Germany	À vérifier
GENOMIT — Global Registry and Natural History Study for Mitochondrial DisordersThe main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.	Myopathies	À vérifier	Remyélinisation indirecte / réparation	Austria, Germany, Italy	À vérifier
clemastine (8 mg/day)Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Cognitive deficits occur as early as the prodromal phase of the illness and significantly determine its outcome. Pathophysiologically, SZ is regarded as a disconnectome disorder in which frontal and temporal brain regions are functionally disconnected, which contributes substantially to the development of cognitive dysfunction. Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, the study will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes.	SEP	Phase 2	Remyélinisation		À vérifier

Essais cliniques

3

Molécule	Indication / population	Phase	NCT	Titre	Statut
clemastine (8 mg/day)	SEP	Phase 2	NCT06315972	OligoTreat — Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity	NOT_YET_RECRUITING
GENOMIT — Global Registry and Natural History Study for Mitochondrial Disorders	Myopathies	À vérifier	NCT05554835	GENOMIT — Global Registry and Natural History Study for Mitochondrial Disorders	RECRUITING
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders	Myopathies	À vérifier	NCT04907162	Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders	COMPLETED

Publications

4

Molécule	Indication / population	Titre	Journal	Date
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders		Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).	Calcified tissue international
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders		Brain signatures of nociplastic pain: Fibromyalgia Index and descending modulation at population level.	Brain : a journal of neurology
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders		Pain in neuromyelitis optica spectrum disorder: determination of prevalence and characteristics.	Acta neurologica Belgica
Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders		Central and Peripheral Sensitization in Temporomandibular Disorders: Proposed Mechanisms of Botulinum Toxin Therapy.	Toxins