Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Clinical Phase
EARLY_PHASE1
Total Enrollment
100 participants
Study Classification
INTERVENTIONAL
Study Start Date
2017-11-22
Study Completion Date
2022-12-01
Brief Summary
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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.
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.
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Detailed Description
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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.
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.
Conditions
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Brain Injuries
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
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 Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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D-aspartato+ET
Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.
Group Type
EXPERIMENTAL
D-Aspartate
Intervention Type
DRUG
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.
Therapeutic exercise
Intervention Type
BEHAVIORAL
Standard physiotherapy
Placebo+ET
Patients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise.
Group Type
PLACEBO_COMPARATOR
Therapeutic exercise
Intervention Type
BEHAVIORAL
Standard physiotherapy
Placebo Oral Tablet
Intervention Type
DRUG
Placebo
Interventions
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D-Aspartate
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.
Intervention Type
DRUG
Therapeutic exercise
Standard physiotherapy
Intervention Type
BEHAVIORAL
Placebo Oral Tablet
Placebo
Intervention Type
DRUG
Other Intervention Names
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DAA, D-Aspartic acid
Physiotherapy
Eligibility Criteria
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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.
* 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.
* 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.
Minimum Eligible Age
18 Years
Maximum Eligible Age
80 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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Neuromed IRCCS
OTHER
Sponsor Role
lead
Responsible Party
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Mario Stampanoni Bassi
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Locations
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IRCCS Neuromed
Pozzilli, Isernia, Italy
Site Status
RECRUITING
Countries
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Italy
Facility Contacts
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References
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Neuromed
Identifier Type: -
Identifier Source: org_study_id
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