ClinicalTrials.gov
ClinicalTrials.gov Menu

D-aspartate and Therapeutic Exercise (DAsp&TerapEx)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03228524
Recruitment Status : Recruiting
First Posted : July 25, 2017
Last Update Posted : November 27, 2017
Sponsor:
Information provided by (Responsible Party):
Neuromed IRCCS

Brief Summary:

An important mechanism responsible for clinical recovery after neurological damage of different types is synaptic plasticity. Nervous tissue can enhance or de-energize inter-neuronal transmission at synaptic level in a lasting way. By increasing the efficiency of synaptic transmission, through long-term potentiation (LTP), it is possible to compensate for the loss of synaptic pulses on survived neurons due to brain damage and to restore their function.

At synaptic level, LTP is mainly regulated by NMDA receptors. In animal models induction of plasticity in surviving neurons through the stimulation of NMDA receptors has been shown to limit the clinical manifestations of neuronal damage. Endogenous NMDA is synthesized by methylation of D-aspartate (Asp) by D-aspartatoartate methyltransferase . Moreover, Asp acts as a neurotransmitter capable of activating the NMDA receptor, since its biosynthesis, degradation, absorption and release occurs in the pre-synaptic neuron, and its release determines a response in Post-synaptic neurons. The expression of Asp in the SNC is very abundant during the embryonic period and in early years, whereas it is significantly reduced in adulthood.

Consistent with Asp ability of activating the NMDA receptor, recent studies have shown that oral administration of Asp increases LTP induction in mice. Preliminary studies by our group also showed an increase in LTP amplitude in subjects suffering from progressive forms of Multiple Sclerosis after 2 weeks of daily per os intake of 2660mg Asp.

It is also well known that the therapeutic exercise that characterizes a rehabilitative treatment is able to induce various benefits to the physical-functional and the cognitive-emotional spheres. In this regard, it has been extensively demonstrated how repeatedly performing a motor task can increase cortical excitability through the induction of LTP mechanisms.

Hypothesis Pharmacologically promoting the induction of cortical LTP by the intake of Asp in subjects with various types of brain damage (eg Multiple Sclerosis, Parkinson's Disease, Dementia) may favor the therapeutic effects of rehabilitative treatment.

Specific Objectives Evaluate the effects of Asp in improving the outcome of rehabilitative treatment resulting from brain damage of different origin.


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
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: D-aspartato+ET
Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.
Drug: 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.
Other Name: DAA, D-Aspartic acid
Behavioral: Therapeutic exercise
Standard physiotherapy
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
Standard physiotherapy
Other Name: Physiotherapy
Drug: Placebo Oral Tablet
Placebo



Primary Outcome Measures :
  1. quality of life [ Time Frame: up to 3 years ]
    Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)

  2. FIM [ Time Frame: up to 3 years ]
    Functional Independence Measurement (FIM) (Chumney et al., 2010)

  3. stroke [ Time Frame: up to 3 years ]
    NIH Stroke Scale / Score (NIHSS)

  4. disability [ Time Frame: up to 3 years ]
    Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)

  5. parkinson [ Time Frame: up to 3 years ]
    Unified Parkinson's Disease Rating Scale (Rammer et al. )

  6. depression [ Time Frame: up to 3 years ]
    Beck Depression Inventory (BDI) (Beck, 1972)

  7. 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).

  8. locomotion and posture [ Time Frame: up to 3 years ]
    Stabilometric Platform

  9. locomotion and posture [ Time Frame: up to 3 years ]
    Gait Analysis

  10. deglutition [ Time Frame: up to 3 years ]
    Ectrophysiological and the Fibroendoscopic Deglutition Study

  11. Cognition [ Time Frame: up to 3 years ]
    ad-hoc tasks



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

This study aims to provide preliminary data on interaction between D-aspartate and therapeutic exercise in inducing LTP cortical phenomena. The sample estimate was made by analogy after a literature analysis. In view of the risk of abandonment quite high, our intention is to recruit at least 100 subjects in a population of patients with cerebral injury of various origin (such as Multiple Sclerosis, Parkinson Disease, Dementia, Skull Trauma, Stroke, Epilepsy or Other Syndromes Neurological character), related to the neurology department of IRRCS Neuromed by Pozzilli.

Inclusion criteria:

  • Males or females aged between 18 and 80;
  • Presence of brain damage resulting from: Multiple Sclerosis, Parkinson's Disease, Dementia, Cranial Trauma, Neurosurgery, Stroke, Epilepsy, or Other Neurological Syndromes;
  • Patient's ability to adhere to the rehabilitation treatment provided for his / her clinical condition by competent personnel;
  • Female subjects can not be pregnant, can not breastfeed, have been born at least three months before the beginning of the study, undertake not to schedule a pregnancy for the duration of the study;
  • Patients should be able to follow protocol guidelines throughout the study;
  • Patients should be able to understand the aims and risks of the study;
  • Signature of informed consent, approved by our Ethics Committee.

Exclusion criteria:

  • Tumors or systemic infections;
  • Patients with impaired hepatic function (ALT> 3 x ULN, Alcaline Phosphatase> 2 x ULN, bilirubin tot> 2 x ULN if associated with any increase in ALT or alkaline phosphatase); Severe or moderate renal failure;
  • Other contraindications or hypersensitivity to D-aspartate or its excipients;
  • Patients with other pathologies which, according to the scientific officer's opinion, prevent recruitment;
  • Patients unable to even partially understand and want.

Information from the National Library of Medicine

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


Locations
Italy
IRCCS Neuromed Recruiting
Pozzilli, Isernia, Italy, 86077
Contact: Stefania Passarelli    +39 0865.915217    direzionescientifica@neuromed.it   
Sponsors and Collaborators
Neuromed IRCCS

Publications:

Responsible Party: Neuromed IRCCS
ClinicalTrials.gov Identifier: NCT03228524     History of Changes
Other Study ID Numbers: Neuromed
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: November 27, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
N-Methylaspartate
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs