Ignite Creation Date:
2024-05-06 @ 8:16 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06315972
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-20
First Post:
2024-03-12
Brief Title:
Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity
Sponsor:
LMU Klinikum
Organization:
LMU Klinikum
Study Overview
Official Title:
Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OligoTreat
Brief Summary:
Schizophrenia SZ is a broad clinical entity characterized by different subjective symptomsbehavioural 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 1072 mgday corresponding to clemastine 8 mgday 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
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 1072 mgday corresponding to clemastine 8 mgday 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None