Brain Injuries Clinical Trial
— DAsp&TerapExOfficial title:
Promotion of Synaptic Plasticity With D-Aspartate to Favour Recovery Form Cerebral Damage
Verified date | March 2019 |
Source | Neuromed IRCCS |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
An important mechanism responsible for clinical recovery after neurological damage of
different types is synaptic plasticity. Nervous tissue can enhance or de-energize
inter-neuronal transmission at synaptic level in a lasting way. By increasing the efficiency
of synaptic transmission, through long-term potentiation (LTP), it is possible to compensate
for the loss of synaptic pulses on survived neurons due to brain damage and to restore their
function.
At synaptic level, LTP is mainly regulated by NMDA receptors. In animal models induction of
plasticity in surviving neurons through the stimulation of NMDA receptors has been shown to
limit the clinical manifestations of neuronal damage. Endogenous NMDA is synthesized by
methylation of D-aspartate (Asp) by D-aspartatoartate methyltransferase . Moreover, Asp acts
as a neurotransmitter capable of activating the NMDA receptor, since its biosynthesis,
degradation, absorption and release occurs in the pre-synaptic neuron, and its release
determines a response in Post-synaptic neurons. The expression of Asp in the SNC is very
abundant during the embryonic period and in early years, whereas it is significantly reduced
in adulthood.
Consistent with Asp ability of activating the NMDA receptor, recent studies have shown that
oral administration of Asp increases LTP induction in mice. Preliminary studies by our group
also showed an increase in LTP amplitude in subjects suffering from progressive forms of
Multiple Sclerosis after 2 weeks of daily per os intake of 2660mg Asp.
It is also well known that the therapeutic exercise that characterizes a rehabilitative
treatment is able to induce various benefits to the physical-functional and the
cognitive-emotional spheres. In this regard, it has been extensively demonstrated how
repeatedly performing a motor task can increase cortical excitability through the induction
of LTP mechanisms.
Hypothesis Pharmacologically promoting the induction of cortical LTP by the intake of Asp in
subjects with various types of brain damage (eg Multiple Sclerosis, Parkinson's Disease,
Dementia) may favor the therapeutic effects of rehabilitative treatment.
Specific Objectives Evaluate the effects of Asp in improving the outcome of rehabilitative
treatment resulting from brain damage of different origin.
Status | Recruiting |
Enrollment | 100 |
Est. completion date | December 1, 2022 |
Est. primary completion date | July 1, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility |
This study aims to provide preliminary data on interaction between D-aspartate and
therapeutic exercise in inducing LTP cortical phenomena. The sample estimate was made by
analogy after a literature analysis. In view of the risk of abandonment quite high, our
intention is to recruit at least 100 subjects in a population of patients with cerebral
injury of various origin (such as Multiple Sclerosis, Parkinson Disease, Dementia, Skull
Trauma, Stroke, Epilepsy or Other Syndromes Neurological character), related to the
neurology department of IRRCS Neuromed by Pozzilli. Inclusion criteria: - Males or females aged between 18 and 80; - Presence of brain damage resulting from: Multiple Sclerosis, Parkinson's Disease, Dementia, Cranial Trauma, Neurosurgery, Stroke, Epilepsy, or Other Neurological Syndromes; - Patient's ability to adhere to the rehabilitation treatment provided for his / her clinical condition by competent personnel; - Female subjects can not be pregnant, can not breastfeed, have been born at least three months before the beginning of the study, undertake not to schedule a pregnancy for the duration of the study; - Patients should be able to follow protocol guidelines throughout the study; - Patients should be able to understand the aims and risks of the study; - Signature of informed consent, approved by our Ethics Committee. Exclusion criteria: - Tumors or systemic infections; - Patients with impaired hepatic function (ALT> 3 x ULN, Alcaline Phosphatase> 2 x ULN, bilirubin tot> 2 x ULN if associated with any increase in ALT or alkaline phosphatase); Severe or moderate renal failure; - Other contraindications or hypersensitivity to D-aspartate or its excipients; - Patients with other pathologies which, according to the scientific officer's opinion, prevent recruitment; - Patients unable to even partially understand and want. |
Country | Name | City | State |
---|---|---|---|
Italy | IRCCS Neuromed | Pozzilli | Isernia |
Lead Sponsor | Collaborator |
---|---|
Neuromed IRCCS |
Italy,
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* Note: There are 50 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007) | quality of life | up to 3 years | |
Primary | FIM | Functional Independence Measurement (FIM) (Chumney et al., 2010) | up to 3 years | |
Primary | stroke | NIH Stroke Scale / Score (NIHSS) | up to 3 years | |
Primary | disability | Expanded Disability Status Scale (EDSS) (Kurtzke, 1983) | up to 3 years | |
Primary | parkinson | Unified Parkinson's Disease Rating Scale (Rammer et al. ) | up to 3 years | |
Primary | depression | Beck Depression Inventory (BDI) (Beck, 1972) | up to 3 years | |
Primary | neuronal plasticity | Transcranial Magnetic Stimulation (TMS) will be used to evaluate the change of neuronal plasticity in a subgroup of patients who will not present contraindications to the method. The TMS uses short-lived magnetic fields and high intensity applied at the scalp level to activate the neurons of a small region of the cerebral cortex through an electromagnetic induction. When these impulses are applied repeatedly, it is possible to induce plastic modification of cortical excitability. If these changes are induced at the level of the motor cortex, they can be measured by recording a motor evoked potential (MEP) at the muscle level represented at the stimulated region level. Any increase or decrease in AMP amplitude, which persists after the end of TMS repetitive stimulation, indicates that there have been changes in the cortical, LTP or depression (LTD). | up to 3 years | |
Primary | locomotion and posture | Stabilometric Platform | up to 3 years | |
Primary | locomotion and posture | Gait Analysis | up to 3 years | |
Primary | deglutition | Ectrophysiological and the Fibroendoscopic Deglutition Study | up to 3 years | |
Primary | Cognition | ad-hoc tasks | up to 3 years |
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