Brain InjuriesEarly Phase 1DAsp&TerapExNCT03228524
D-aspartate and Therapeutic Exercise
A Early Phase 1 study testing D-Aspartate and Therapeutic exercise in people with Brain Injuries, run by Neuromed IRCCS at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Injuries
- What is being tested?
- D-Aspartate and Therapeutic exercise
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 22 Nov 2017to 1 Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Neuromed
Pozzilli, Isernia, 86077
Stefania Passarelli, +39 0865.915217, direzionescientifica@neuromed.it
About this study
Official title: Promotion of Synaptic Plasticity With D-Aspartate to Favour Recovery Form Cerebral Damage
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Brain Injuries
- Being tested
- D-Aspartate, Therapeutic exercise, Placebo Oral Tablet
- Medical subject headings
- Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-AspartateDrug
Also called DAA, D-Aspartic acid
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 exerciseBehavioural
Also called Physiotherapy
Standard physiotherapy
Placebo Oral TabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| D-aspartato+ET | Experimental | Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise. Receives: Drug: D-Aspartate; Behavioral: Therapeutic exercise |
| Placebo+ET | Placebo comparator | Patients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise. Receives: Behavioral: Therapeutic exercise; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)
quality of life
Measured: up to 3 years
FIM
Functional Independence Measurement (FIM) (Chumney et al., 2010)
Measured: up to 3 years
stroke
NIH Stroke Scale / Score (NIHSS)
Measured: up to 3 years
disability
Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)
Measured: up to 3 years
parkinson
Unified Parkinson's Disease Rating Scale (Rammer et al. )
Measured: up to 3 years
depression
Beck Depression Inventory (BDI) (Beck, 1972)
Measured: up to 3 years
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).
Measured: up to 3 years
locomotion and posture
Stabilometric Platform
Measured: up to 3 years
locomotion and posture
Gait Analysis
Measured: up to 3 years
deglutition
Ectrophysiological and the Fibroendoscopic Deglutition Study
Measured: up to 3 years
Cognition
ad-hoc tasks
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2017
- Study start22 Nov 2017
- Primary completion1 Jul 2020 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (50)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neuromed IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mario Stampanoni Bassi, Neuromed IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03228524
- Sponsor's protocol ID
- Neuromed
- Acronym
- DAsp&TerapEx
- Status last verified
- Mar 2019
- First submitted
- 12 Jul 2017
- Last updated
- 15 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baker R, McGinley JL, Schwartz MH, Beynon S, Rozumalski A, Graham HK, Tirosh O. The gait profile score and movement analysis profile. Gait Posture. 2009 Oct;30(3):265-9. doi: 10.1016/j.gaitpost.2009.05.020. Epub 2009 Jul 24.
PubMed 19632117Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002 Jun;15(3):239-45. doi: 10.1097/00019052-200206000-00003.
PubMed 12045719Bartlett TE, Wang YT. The intersections of NMDAR-dependent synaptic plasticity and cell survival. Neuropharmacology. 2013 Nov;74:59-68. doi: 10.1016/j.neuropharm.2013.01.012. Epub 2013 Jan 25.
PubMed 23357336Bliss TV, Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):331-56. doi: 10.1113/jphysiol.1973.sp010273.
PubMed 4727084Nogueira LA, Teixeira L, Sabino P, Filho HA, Alvarenga RM, Thuler LC. Gait characteristics of multiple sclerosis patients in the absence of clinical disability. Disabil Rehabil. 2013 Aug;35(17):1472-8. doi: 10.3109/09638288.2012.738760.
PubMed 23869824Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, Grossi K, Torelli F, Prosperetti C, Cervellino A, Marfia GA, Stanzione P, Marciani MG, Boffa L, Bernardi G. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50. doi: 10.1212/01.wnl.0000257818.16952.62.
PubMed 17389310Centonze D, Rossi S, Tortiglione A, Picconi B, Prosperetti C, De Chiara V, Bernardi G, Calabresi P. Synaptic plasticity during recovery from permanent occlusion of the middle cerebral artery. Neurobiol Dis. 2007 Jul;27(1):44-53. doi: 10.1016/j.nbd.2007.03.012. Epub 2007 Apr 5.
PubMed 17490888Mori F, Rossi S, Piccinin S, Motta C, Mango D, Kusayanagi H, Bergami A, Studer V, Nicoletti CG, Buttari F, Barbieri F, Mercuri NB, Martino G, Furlan R, Nistico R, Centonze D. Synaptic plasticity and PDGF signaling defects underlie clinical progression in multiple sclerosis. J Neurosci. 2013 Dec 4;33(49):19112-9. doi: 10.1523/JNEUROSCI.2536-13.2013.
PubMed 24305808Chang PL, Isaacs KR, Greenough WT. Synapse formation occurs in association with the induction of long-term potentiation in two-year-old rat hippocampus in vitro. Neurobiol Aging. 1991 Sep-Oct;12(5):517-22. doi: 10.1016/0197-4580(91)90082-u.
PubMed 1770987Chumney D, Nollinger K, Shesko K, Skop K, Spencer M, Newton RA. Ability of Functional Independence Measure to accurately predict functional outcome of stroke-specific population: systematic review. J Rehabil Res Dev. 2010;47(1):17-29. doi: 10.1682/jrrd.2009.08.0140.
PubMed 20437324Ramaker C, Marinus J, Stiggelbout AM, Van Hilten BJ. Systematic evaluation of rating scales for impairment and disability in Parkinson's disease. Mov Disord. 2002 Sep;17(5):867-76. doi: 10.1002/mds.10248.
PubMed 12360535Comber L, Galvin R, Coote S. Gait deficits in people with multiple sclerosis: A systematic review and meta-analysis. Gait Posture. 2017 Jan;51:25-35. doi: 10.1016/j.gaitpost.2016.09.026. Epub 2016 Sep 26.
PubMed 27693958Compston A, Coles A. Multiple sclerosis. Lancet. 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X.
PubMed 11955556D'Aniello A, Di Fiore MM, Fisher GH, Milone A, Seleni A, D'Aniello S, Perna AF, Ingrosso D. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release. FASEB J. 2000 Apr;14(5):699-714. doi: 10.1096/fasebj.14.5.699.
PubMed 10744627Di Lazzaro V, Profice P, Pilato F, Capone F, Ranieri F, Pasqualetti P, Colosimo C, Pravata E, Cianfoni A, Dileone M. Motor cortex plasticity predicts recovery in acute stroke. Cereb Cortex. 2010 Jul;20(7):1523-8. doi: 10.1093/cercor/bhp216. Epub 2009 Oct 5.
PubMed 19805417
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Promotion of Synaptic Plasticity With D-Aspartate to Favour Recovery Form Cerebral Damage
- ClinicalTrials.gov ID
- NCT03228524
- Acronym / sponsor ID
- DAsp&TerapEx / Neuromed
- Conditions
- Brain Injuries
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Neuromed IRCCSUniversity, hospital or other
- Study start
- 22 Nov 2017 (actual)
- Primary completion
- 1 Jul 2020 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 25 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| D-aspartato+ET | Experimental | Drug: D-Aspartate, Behavioral: Therapeutic exercisePatients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise. |
| Placebo+ET | Placebo comparator | Behavioral: Therapeutic exercise, Drug: Placebo Oral TabletPatients will be administered oral placebo for 6 weks. Moreover, patients will receive therapeutic exercise. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-AspartateAlso: DAA, D-Aspartic acidPatients 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. | Drug | D-aspartato+ET |
| Therapeutic exerciseAlso: PhysiotherapyStandard physiotherapy | Behavioural | D-aspartato+ET, Placebo+ET |
| Placebo Oral TabletPlacebo | Drug | Placebo+ET |
Primary outcome
Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)
Time frame: up to 3 years
quality of life
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2019.
- Background: PubMed 19632117Baker R, McGinley JL, Schwartz MH, Beynon S, Rozumalski A, Graham HK, Tirosh O. The gait profile score and movement analysis profile. Gait Posture. 2009 Oct;30(3):265-9. doi: 10.1016/j.gaitpost.2009.05.020. Epub 2009 Jul 24.
- Background: PubMed 12045719Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002 Jun;15(3):239-45. doi: 10.1097/00019052-200206000-00003.
- Background: PubMed 23357336Bartlett TE, Wang YT. The intersections of NMDAR-dependent synaptic plasticity and cell survival. Neuropharmacology. 2013 Nov;74:59-68. doi: 10.1016/j.neuropharm.2013.01.012. Epub 2013 Jan 25.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing D-Aspartate and Therapeutic exercise in people with Brain Injuries, run by Neuromed IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007) (time frame: up to 3 years). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03228524, which also lists 50 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019.