D-aspartate and Therapeutic Exercise

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Neuromed IRCCS
• Treatments: N-Methylaspartate

Criteria

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.