D-aspartate and Therapeutic Exercise (DAsp&TerapEx)
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|ClinicalTrials.gov Identifier: NCT03228524|
Recruitment Status : Recruiting
First Posted : July 25, 2017
Last Update Posted : November 27, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain Injuries||Drug: D-Aspartate Behavioral: Therapeutic exercise Drug: Placebo Oral Tablet||Early Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Recruited patients will be randomized to receive 2660 mg D-aspartate oral dosing once daily or placebo, in addition to the conventional treatment provided by the relevant staff, for a period of 6 weeks. Patients will also be undergoing a Therapeutic Exercise Program (ET). All conventional therapies taken by patients will be recorded by the operators. Patients will be divided into two D-aspartate + ET and Placebo + ET groups and will be evaluated at zero time before starting treatment (T-0W) after 6 weeks to evaluate the effects at the end of treatment (T-6W) , And at 12 weeks (T-12W) to evaluate the maintenance of long-term effects.|
|Masking:||None (Open Label)|
|Official Title:||Promotion of Synaptic Plasticity With D-Aspartate to Favour Recovery Form Cerebral Damage|
|Actual Study Start Date :||November 22, 2017|
|Estimated Primary Completion Date :||July 1, 2018|
|Estimated Study Completion Date :||December 1, 2022|
Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.
Patients will be randomized to receive oral D-aspartatoe (2660 mg, once daily) or placebo,as an addition to conventional therapy as indicated by physicians, for a 6 weeks period.
Other Name: DAA, D-Aspartic acid
Behavioral: Therapeutic exercise
Other Name: Physiotherapy
Placebo Comparator: Placebo+ET
Patients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise.
Behavioral: Therapeutic exercise
Other Name: Physiotherapy
Drug: Placebo Oral Tablet
- quality of life [ Time Frame: up to 3 years ]Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)
- FIM [ Time Frame: up to 3 years ]Functional Independence Measurement (FIM) (Chumney et al., 2010)
- stroke [ Time Frame: up to 3 years ]NIH Stroke Scale / Score (NIHSS)
- disability [ Time Frame: up to 3 years ]Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)
- parkinson [ Time Frame: up to 3 years ]Unified Parkinson's Disease Rating Scale (Rammer et al. )
- depression [ Time Frame: up to 3 years ]Beck Depression Inventory (BDI) (Beck, 1972)
- neuronal plasticity [ Time Frame: up to 3 years ]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).
- locomotion and posture [ Time Frame: up to 3 years ]Stabilometric Platform
- locomotion and posture [ Time Frame: up to 3 years ]Gait Analysis
- deglutition [ Time Frame: up to 3 years ]Ectrophysiological and the Fibroendoscopic Deglutition Study
- Cognition [ Time Frame: up to 3 years ]ad-hoc tasks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03228524
|Pozzilli, Isernia, Italy, 86077|
|Contact: Stefania Passarelli +39 0865.915217 email@example.com|