<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03228524</url>
  </required_header>
  <id_info>
    <org_study_id>Neuromed</org_study_id>
    <nct_id>NCT03228524</nct_id>
  </id_info>
  <brief_title>D-aspartate and Therapeutic Exercise</brief_title>
  <acronym>DAsp&amp;TerapEx</acronym>
  <official_title>Promotion of Synaptic Plasticity With D-Aspartate to Favour Recovery Form Cerebral Damage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neuromed IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neuromed IRCCS</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An important mechanism responsible for clinical recovery after neurological damage of&#xD;
      different types is synaptic plasticity. Nervous tissue can enhance or de-energize&#xD;
      inter-neuronal transmission at synaptic level in a lasting way. By increasing the efficiency&#xD;
      of synaptic transmission, through long-term potentiation (LTP), it is possible to compensate&#xD;
      for the loss of synaptic pulses on survived neurons due to brain damage and to restore their&#xD;
      function.&#xD;
&#xD;
      At synaptic level, LTP is mainly regulated by NMDA receptors. In animal models induction of&#xD;
      plasticity in surviving neurons through the stimulation of NMDA receptors has been shown to&#xD;
      limit the clinical manifestations of neuronal damage. Endogenous NMDA is synthesized by&#xD;
      methylation of D-aspartate (Asp) by D-aspartatoartate methyltransferase . Moreover, Asp acts&#xD;
      as a neurotransmitter capable of activating the NMDA receptor, since its biosynthesis,&#xD;
      degradation, absorption and release occurs in the pre-synaptic neuron, and its release&#xD;
      determines a response in Post-synaptic neurons. The expression of Asp in the SNC is very&#xD;
      abundant during the embryonic period and in early years, whereas it is significantly reduced&#xD;
      in adulthood.&#xD;
&#xD;
      Consistent with Asp ability of activating the NMDA receptor, recent studies have shown that&#xD;
      oral administration of Asp increases LTP induction in mice. Preliminary studies by our group&#xD;
      also showed an increase in LTP amplitude in subjects suffering from progressive forms of&#xD;
      Multiple Sclerosis after 2 weeks of daily per os intake of 2660mg Asp.&#xD;
&#xD;
      It is also well known that the therapeutic exercise that characterizes a rehabilitative&#xD;
      treatment is able to induce various benefits to the physical-functional and the&#xD;
      cognitive-emotional spheres. In this regard, it has been extensively demonstrated how&#xD;
      repeatedly performing a motor task can increase cortical excitability through the induction&#xD;
      of LTP mechanisms.&#xD;
&#xD;
      Hypothesis Pharmacologically promoting the induction of cortical LTP by the intake of Asp in&#xD;
      subjects with various types of brain damage (eg Multiple Sclerosis, Parkinson's Disease,&#xD;
      Dementia) may favor the therapeutic effects of rehabilitative treatment.&#xD;
&#xD;
      Specific Objectives Evaluate the effects of Asp in improving the outcome of rehabilitative&#xD;
      treatment resulting from brain damage of different origin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An important mechanism responsible for clinical recovery after neurological damage of&#xD;
      different types is synaptic plasticity. Nervous tissue can enhance or de-energize&#xD;
      inter-neuronal transmission at synaptic level in a lasting way. By increasing the efficiency&#xD;
      of synaptic transmission, through long-term potentiation (LTP), it is possible to compensate&#xD;
      for the loss of synaptic pulses on survived neurons due to brain damage and to restore their&#xD;
      function.&#xD;
&#xD;
      At synaptic level, LTP is mainly regulated by NMDA receptors. In animal models induction of&#xD;
      plasticity in surviving neurons through the stimulation of NMDA receptors has been shown to&#xD;
      limit the clinical manifestations of neuronal damage. Endogenous NMDA is synthesized by&#xD;
      methylation of D-aspartate (Asp) by D-aspartatoartate methyltransferase . Moreover, Asp acts&#xD;
      as a neurotransmitter capable of activating the NMDA receptor, since its biosynthesis,&#xD;
      degradation, absorption and release occurs in the pre-synaptic neuron, and its release&#xD;
      determines a response in Post-synaptic neurons. The expression of Asp in the SNC is very&#xD;
      abundant during the embryonic period and in early years, whereas it is significantly reduced&#xD;
      in adulthood.&#xD;
&#xD;
      Consistent with Asp ability of activating the NMDA receptor, recent studies have shown that&#xD;
      oral administration of Asp increases LTP induction in mice. Preliminary studies by our group&#xD;
      also showed an increase in LTP amplitude in subjects suffering from progressive forms of&#xD;
      Multiple Sclerosis after 2 weeks of daily per os intake of 2660mg Asp.&#xD;
&#xD;
      It is also well known that the therapeutic exercise that characterizes a rehabilitative&#xD;
      treatment is able to induce various benefits to the physical-functional and the&#xD;
      cognitive-emotional spheres. In this regard, it has been extensively demonstrated how&#xD;
      repeatedly performing a motor task can increase cortical excitability through the induction&#xD;
      of LTP mechanisms.&#xD;
&#xD;
      Hypothesis Pharmacologically promoting the induction of cortical LTP by the intake of Asp in&#xD;
      subjects with various types of brain damage (eg Multiple Sclerosis, Parkinson's Disease,&#xD;
      Dementia) may favor the therapeutic effects of rehabilitative treatment.&#xD;
&#xD;
      Specific Objectives A double-blind study to evaluate the effects of D-aspartate in improving&#xD;
      the outcome of rehabilitative treatment resulting from brain damage of different origin (eg&#xD;
      Multiple Sclerosis, Parkinson's Disease, Dementia). This will be made possible thanks to the&#xD;
      specific skills of a multidisciplinary team of neurologists and physiatrists, healthcare&#xD;
      professionals such as physiotherapists, occupational therapists, psychologists, speech&#xD;
      therapists and the support of a biomedical engineer. These professional figures are already&#xD;
      available at the UCK Neurosurgery of the IRCCS Neuromed directed by the proposer and actively&#xD;
      collaborate to optimize the therapeutic exercise of patients with neurological damage.&#xD;
&#xD;
      Population of the study This study aims to provide preliminary data on interaction between&#xD;
      D-aspartate and therapeutic exercise in inducing LTP cortical phenomena. The sample estimate&#xD;
      was made by analogy after a literature analysis. In view of the quite high risk of drop out,&#xD;
      our intention is to recruit at least 100 subjects in a population of patients with cerebral&#xD;
      injury of various origin, coming to the neurology department of IRRCS Neuromed, Pozzilli.&#xD;
&#xD;
      Inclusion and exclusion criteria are as specified below.&#xD;
&#xD;
      Study design Double-blind prospective study, between randomized, placebo-controlled parallel&#xD;
      groups.&#xD;
&#xD;
      Recruited patients will be randomized to receive 2660 mg D-aspartate oral dosing once daily&#xD;
      or placebo, in addition to the conventional treatment provided by the relevant staff, for a&#xD;
      period of 6 weeks. Patients will also be undergoing a Therapeutic Exercise Program (ET). All&#xD;
      conventional therapies taken by patients will be recorded by the operators. Patients will be&#xD;
      evaluated at zero time before starting treatment (T-0W) after 6 weeks to evaluate the effects&#xD;
      at the end of treatment (T-6W) , and at 12 weeks (T-12W) to evaluate the maintenance of&#xD;
      long-term effects. Randomization will be balanced in accordance with age, sex and schooling.&#xD;
&#xD;
      The physiotherapy and/or speech therapy approach will differ among patients considering the&#xD;
      different types of brain damage and the different levels of disability, according to the&#xD;
      rehabilitation unit team for each case.&#xD;
&#xD;
      Expected results The present study aims to investigate whether the association between&#xD;
      pharmacological treatment with D-aspartate and therapeutic exercise may be more effective&#xD;
      than just therapeutic exercise in favor of synaptic plasticity and clinical recovery under&#xD;
      it, in patients with various forms of brain damage.&#xD;
&#xD;
      The expected result based on previous studies on mice (Errico, 2008, Errico, 2011) is that&#xD;
      D-aspartate, promoting neuronal plasticity and acting in synergy with therapeutic exercise,&#xD;
      strengthens the recovery of deficits in patients with various types of brain damage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 22, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)</measure>
    <time_frame>up to 3 years</time_frame>
    <description>quality of life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FIM</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Functional Independence Measurement (FIM) (Chumney et al., 2010)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>stroke</measure>
    <time_frame>up to 3 years</time_frame>
    <description>NIH Stroke Scale / Score (NIHSS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>disability</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>parkinson</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Unified Parkinson's Disease Rating Scale (Rammer et al. )</description>
  </primary_outcome>
  <primary_outcome>
    <measure>depression</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Beck Depression Inventory (BDI) (Beck, 1972)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neuronal plasticity</measure>
    <time_frame>up to 3 years</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>locomotion and posture</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Stabilometric Platform</description>
  </primary_outcome>
  <primary_outcome>
    <measure>locomotion and posture</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Gait Analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>deglutition</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Ectrophysiological and the Fibroendoscopic Deglutition Study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognition</measure>
    <time_frame>up to 3 years</time_frame>
    <description>ad-hoc tasks</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Brain Injuries</condition>
  <arm_group>
    <arm_group_label>D-aspartato+ET</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo+ET</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>D-Aspartate</intervention_name>
    <description>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.</description>
    <arm_group_label>D-aspartato+ET</arm_group_label>
    <other_name>DAA, D-Aspartic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Therapeutic exercise</intervention_name>
    <description>Standard physiotherapy</description>
    <arm_group_label>D-aspartato+ET</arm_group_label>
    <arm_group_label>Placebo+ET</arm_group_label>
    <other_name>Physiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo+ET</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        This study aims to provide preliminary data on interaction between D-aspartate and&#xD;
        therapeutic exercise in inducing LTP cortical phenomena. The sample estimate was made by&#xD;
        analogy after a literature analysis. In view of the risk of abandonment quite high, our&#xD;
        intention is to recruit at least 100 subjects in a population of patients with cerebral&#xD;
        injury of various origin (such as Multiple Sclerosis, Parkinson Disease, Dementia, Skull&#xD;
        Trauma, Stroke, Epilepsy or Other Syndromes Neurological character), related to the&#xD;
        neurology department of IRRCS Neuromed by Pozzilli.&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Males or females aged between 18 and 80;&#xD;
&#xD;
          -  Presence of brain damage resulting from: Multiple Sclerosis, Parkinson's Disease,&#xD;
             Dementia, Cranial Trauma, Neurosurgery, Stroke, Epilepsy, or Other Neurological&#xD;
             Syndromes;&#xD;
&#xD;
          -  Patient's ability to adhere to the rehabilitation treatment provided for his / her&#xD;
             clinical condition by competent personnel;&#xD;
&#xD;
          -  Female subjects can not be pregnant, can not breastfeed, have been born at least three&#xD;
             months before the beginning of the study, undertake not to schedule a pregnancy for&#xD;
             the duration of the study;&#xD;
&#xD;
          -  Patients should be able to follow protocol guidelines throughout the study;&#xD;
&#xD;
          -  Patients should be able to understand the aims and risks of the study;&#xD;
&#xD;
          -  Signature of informed consent, approved by our Ethics Committee.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Tumors or systemic infections;&#xD;
&#xD;
          -  Patients with impaired hepatic function (ALT&gt; 3 x ULN, Alcaline Phosphatase&gt; 2 x ULN,&#xD;
             bilirubin tot&gt; 2 x ULN if associated with any increase in ALT or alkaline&#xD;
             phosphatase); Severe or moderate renal failure;&#xD;
&#xD;
          -  Other contraindications or hypersensitivity to D-aspartate or its excipients;&#xD;
&#xD;
          -  Patients with other pathologies which, according to the scientific officer's opinion,&#xD;
             prevent recruitment;&#xD;
&#xD;
          -  Patients unable to even partially understand and want.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>IRCCS Neuromed</name>
      <address>
        <city>Pozzilli</city>
        <state>Isernia</state>
        <zip>86077</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefania Passarelli</last_name>
      <phone>+39 0865.915217</phone>
      <email>direzionescientifica@neuromed.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
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  <verification_date>March 2019</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>March 13, 2019</last_update_submitted>
  <last_update_submitted_qc>March 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Neuromed IRCCS</investigator_affiliation>
    <investigator_full_name>Mario Stampanoni Bassi</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03228524
org study id: Neuromed
nct id: NCT03228524
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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 A double-blind study to evaluate the effects of D-aspartate in improving
      the outcome of rehabilitative treatment resulting from brain damage of different origin (eg
      Multiple Sclerosis, Parkinson's Disease, Dementia). This will be made possible thanks to the
      specific skills of a multidisciplinary team of neurologists and physiatrists, healthcare
      professionals such as physiotherapists, occupational therapists, psychologists, speech
      therapists and the support of a biomedical engineer. These professional figures are already
      available at the UCK Neurosurgery of the IRCCS Neuromed directed by the proposer and actively
      collaborate to optimize the therapeutic exercise of patients with neurological damage.

      Population of the study 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 quite high risk of drop out,
      our intention is to recruit at least 100 subjects in a population of patients with cerebral
      injury of various origin, coming to the neurology department of IRRCS Neuromed, Pozzilli.

      Inclusion and exclusion criteria are as specified below.

      Study design Double-blind prospective study, between randomized, placebo-controlled parallel
      groups.

      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
      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. Randomization will be balanced in accordance with age, sex and schooling.

      The physiotherapy and/or speech therapy approach will differ among patients considering the
      different types of brain damage and the different levels of disability, according to the
      rehabilitation unit team for each case.

      Expected results The present study aims to investigate whether the association between
      pharmacological treatment with D-aspartate and therapeutic exercise may be more effective
      than just therapeutic exercise in favor of synaptic plasticity and clinical recovery under
      it, in patients with various forms of brain damage.

      The expected result based on previous studies on mice (Errico, 2008, Errico, 2011) is that
      D-aspartate, promoting neuronal plasticity and acting in synergy with therapeutic exercise,
      strengthens the recovery of deficits in patients with various types of brain damage.
allocation: Randomized
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.
primary purpose: Treatment
masking: None (Open Label)
measure: Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)
time frame: up to 3 years
description: quality of life
measure: FIM
time frame: up to 3 years
description: Functional Independence Measurement (FIM) (Chumney et al., 2010)
measure: stroke
time frame: up to 3 years
description: NIH Stroke Scale / Score (NIHSS)
measure: disability
time frame: up to 3 years
description: Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)
measure: parkinson
time frame: up to 3 years
description: Unified Parkinson's Disease Rating Scale (Rammer et al. )
measure: depression
time frame: up to 3 years
description: Beck Depression Inventory (BDI) (Beck, 1972)
measure: neuronal plasticity
time frame: up to 3 years
description: 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).
measure: locomotion and posture
time frame: up to 3 years
description: Stabilometric Platform
measure: locomotion and posture
time frame: up to 3 years
description: Gait Analysis
measure: deglutition
time frame: up to 3 years
description: Ectrophysiological and the Fibroendoscopic Deglutition Study
measure: Cognition
time frame: up to 3 years
description: ad-hoc tasks
arm group label: D-aspartato+ET
arm group type: Experimental
description: Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.
arm group label: Placebo+ET
arm group type: Placebo Comparator
description: Patients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise.
intervention type: Drug
intervention name: D-Aspartate
description: 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.
arm group label: D-aspartato+ET
other name: DAA, D-Aspartic acid
intervention type: Behavioral
intervention name: Therapeutic exercise
description: Standard physiotherapy
arm group label: D-aspartato+ET
arm group label: Placebo+ET
other name: Physiotherapy
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Placebo
arm group label: Placebo+ET
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
status: Recruiting
contact: 
country: Italy
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responsible party type: Principal Investigator
investigator affiliation: Neuromed IRCCS
investigator full name: Mario Stampanoni Bassi
investigator title: Principal Investigator
mesh term: Brain Injuries
sharing ipd: No