D-aspartate and Therapeutic Exercise

NCT03228524 | Unknown Early Phase 1

• 1 other identifier: Neuromed
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Injuries

Outcome Measures

Primary Outcomes (11)

• Barthel's Activities of Daily Living (ADL) (O'Sullivan et al 2007)

  quality of life

  up to 3 years

• FIM

  Functional Independence Measurement (FIM) (Chumney et al., 2010)

  up to 3 years

• stroke

  NIH Stroke Scale / Score (NIHSS)

  up to 3 years

• disability

  Expanded Disability Status Scale (EDSS) (Kurtzke, 1983)

  up to 3 years

• parkinson

  Unified Parkinson's Disease Rating Scale (Rammer et al. )

  up to 3 years

• depression

  Beck Depression Inventory (BDI) (Beck, 1972)

  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).

  up to 3 years

• locomotion and posture

  Stabilometric Platform

  up to 3 years

• locomotion and posture

  Gait Analysis

  up to 3 years

• deglutition

  Ectrophysiological and the Fibroendoscopic Deglutition Study

  up to 3 years

• Cognition

  ad-hoc tasks

  up to 3 years

Study Arms (2)

D-aspartato+ET

EXPERIMENTAL

Patients will be administered oral D-aspartate (2660 mg once daily) for 6 weks. Moreover, patients will receive therapeutic exercise.

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.

Behavioral: Therapeutic exercise; Drug: Placebo Oral Tablet

Interventions

D-Aspartate 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.

Also known as: DAA, D-Aspartic acid

D-aspartato+ET

Therapeutic exercise BEHAVIORAL

Standard physiotherapy

Also known as: Physiotherapy

D-aspartato+ET; Placebo+ET

Placebo Oral Tablet DRUG

Placebo

Placebo+ET

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neuromed IRCCS: lead

Study Sites (1)

IRCCS Neuromed

Pozzilli, Isernia, 86077, Italy

RECRUITING

Related Publications (50)

• 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.

  PMID: 19632117 BACKGROUND

• Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002 Jun;15(3):239-45. doi: 10.1097/00019052-200206000-00003.

  PMID: 12045719 BACKGROUND

• Bartlett 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.

  PMID: 23357336 BACKGROUND

• Bliss 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.

  PMID: 4727084 BACKGROUND

• Nogueira 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.

  PMID: 23869824 BACKGROUND

• Centonze 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.

  PMID: 17389310 BACKGROUND

• Centonze 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.

  PMID: 17490888 BACKGROUND

• Mori 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.

  PMID: 24305808 BACKGROUND

• Chang 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.

  PMID: 1770987 BACKGROUND

• Chumney 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.

  PMID: 20437324 BACKGROUND

• Ramaker 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.

  PMID: 12360535 BACKGROUND

• Comber 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.

  PMID: 27693958 BACKGROUND

• Compston A, Coles A. Multiple sclerosis. Lancet. 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X.

  PMID: 11955556 BACKGROUND

• D'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.

  PMID: 10744627 BACKGROUND

• Di 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.

  PMID: 19805417 BACKGROUND

• Duncan ID, Brower A, Kondo Y, Curlee JF Jr, Schultz RD. Extensive remyelination of the CNS leads to functional recovery. Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6832-6. doi: 10.1073/pnas.0812500106. Epub 2009 Apr 2.

  PMID: 19342494 BACKGROUND

• Errico F, Nistico R, Napolitano F, Mazzola C, Astone D, Pisapia T, Giustizieri M, D'Aniello A, Mercuri NB, Usiello A. Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging. 2011 Dec;32(12):2229-43. doi: 10.1016/j.neurobiolaging.2010.01.002. Epub 2010 Jan 25.

  PMID: 20097447 BACKGROUND

• Errico F, Nistico R, Palma G, Federici M, Affuso A, Brilli E, Topo E, Centonze D, Bernardi G, Bozzi Y, D'Aniello A, Di Lauro R, Mercuri NB, Usiello A. Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci. 2008 Feb;37(2):236-46. doi: 10.1016/j.mcn.2007.09.012. Epub 2007 Oct 5.

  PMID: 17981050 BACKGROUND

• Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. doi: 10.1016/j.neuron.2007.06.026.

  PMID: 17640522 BACKGROUND

• Irvine KA, Blakemore WF. Remyelination protects axons from demyelination-associated axon degeneration. Brain. 2008 Jun;131(Pt 6):1464-77. doi: 10.1093/brain/awn080. Epub 2008 May 18.

  PMID: 18490361 BACKGROUND

• Kalron A, Nitzani D, Magalashvili D, Dolev M, Menascu S, Stern Y, Rosenblum U, Pasitselsky D, Frid L, Zeilig G, Barmatz C, Givon U, Achiron A. A personalized, intense physical rehabilitation program improves walking in people with multiple sclerosis presenting with different levels of disability: a retrospective cohort. BMC Neurol. 2015 Mar 4;15:21. doi: 10.1186/s12883-015-0281-9.

  PMID: 25884887 BACKGROUND

• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.

  PMID: 6685237 BACKGROUND

• Lamprecht R, LeDoux J. Structural plasticity and memory. Nat Rev Neurosci. 2004 Jan;5(1):45-54. doi: 10.1038/nrn1301. No abstract available.

  PMID: 14708003 BACKGROUND

• Li R, Huang FS, Abbas AK, Wigstrom H. Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity. BMC Neurosci. 2007 Jul 26;8:55. doi: 10.1186/1471-2202-8-55.

  PMID: 17655746 BACKGROUND

• Malenka RC, Nicoll RA. NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci. 1993 Dec;16(12):521-7. doi: 10.1016/0166-2236(93)90197-t.

  PMID: 7509523 BACKGROUND

• Maletic-Savatic M, Malinow R, Svoboda K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science. 1999 Mar 19;283(5409):1923-7. doi: 10.1126/science.283.5409.1923.

  PMID: 10082466 BACKGROUND

• Mattson MP. Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res. 1988 Apr-Jun;472(2):179-212. doi: 10.1016/0165-0173(88)90020-3.

  PMID: 2898278 BACKGROUND

• Molina-Luna K, Pekanovic A, Rohrich S, Hertler B, Schubring-Giese M, Rioult-Pedotti MS, Luft AR. Dopamine in motor cortex is necessary for skill learning and synaptic plasticity. PLoS One. 2009 Sep 17;4(9):e7082. doi: 10.1371/journal.pone.0007082.

  PMID: 19759902 BACKGROUND

• Mori F, Codeca C, Kusayanagi H, Monteleone F, Boffa L, Rimano A, Bernardi G, Koch G, Centonze D. Effects of intermittent theta burst stimulation on spasticity in patients with multiple sclerosis. Eur J Neurol. 2010 Feb;17(2):295-300. doi: 10.1111/j.1468-1331.2009.02806.x. Epub 2009 Oct 23.

  PMID: 19863647 BACKGROUND

• Mori F, Kusayanagi H, Nicoletti CG, Weiss S, Marciani MG, Centonze D. Cortical plasticity predicts recovery from relapse in multiple sclerosis. Mult Scler. 2014 Apr;20(4):451-7. doi: 10.1177/1352458513512541. Epub 2013 Nov 21.

  PMID: 24263385 BACKGROUND

• Mostert S, Kesselring J. Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Mult Scler. 2002 Apr;8(2):161-8. doi: 10.1191/1352458502ms779oa.

  PMID: 11990874 BACKGROUND

• Motl RW, McAuley E. Longitudinal analysis of physical activity and symptoms as predictors of change in functional limitations and disability in multiple sclerosis. Rehabil Psychol. 2009 May;54(2):204-10. doi: 10.1037/a0015770.

  PMID: 19469611 BACKGROUND

• Ota N, Shi T, Sweedler JV. D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids. 2012 Nov;43(5):1873-86. doi: 10.1007/s00726-012-1364-1. Epub 2012 Aug 8.

  PMID: 22872108 BACKGROUND

• Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Bruck W, Lucchinetti C, Lassmann H. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006 Dec;129(Pt 12):3165-72. doi: 10.1093/brain/awl217. Epub 2006 Aug 18.

  PMID: 16921173 BACKGROUND

• Pau M, Coghe G, Corona F, Marrosu MG, Cocco E. Effect of spasticity on kinematics of gait and muscular activation in people with Multiple Sclerosis. J Neurol Sci. 2015 Nov 15;358(1-2):339-44. doi: 10.1016/j.jns.2015.09.352. Epub 2015 Sep 18.

  PMID: 26409825 BACKGROUND

• Pau M, Coghe G, Atzeni C, Corona F, Pilloni G, Marrosu MG, Cocco E, Galli M. Novel characterization of gait impairments in people with multiple sclerosis by means of the gait profile score. J Neurol Sci. 2014 Oct 15;345(1-2):159-63. doi: 10.1016/j.jns.2014.07.032. Epub 2014 Jul 19.

  PMID: 25073571 BACKGROUND

• Richards DA, Mateos JM, Hugel S, de Paola V, Caroni P, Gahwiler BH, McKinney RA. Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6166-71. doi: 10.1073/pnas.0501881102. Epub 2005 Apr 14.

  PMID: 15831587 BACKGROUND

• Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

  PMID: 19833552 BACKGROUND

• Schirmer L, Merkler D, Konig FB, Bruck W, Stadelmann C. Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in traumatic brain injury lesions. Brain Pathol. 2013 Jan;23(1):2-12. doi: 10.1111/j.1750-3639.2012.00608.x. Epub 2012 Jun 25.

  PMID: 22612622 BACKGROUND

• Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, Malinow R. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science. 1999 Jun 11;284(5421):1811-6. doi: 10.1126/science.284.5421.1811.

  PMID: 10364548 BACKGROUND

• Singer BH, Gamelli AE, Fuller CL, Temme SJ, Parent JM, Murphy GG. Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5437-42. doi: 10.1073/pnas.1015425108. Epub 2011 Mar 14.

  PMID: 21402918 BACKGROUND

• Solari A, Filippini G, Mendozzi L, Ghezzi A, Cifani S, Barbieri E, Baldini S, Salmaggi A, Mantia LL, Farinotti M, Caputo D, Mosconi P. Validation of Italian multiple sclerosis quality of life 54 questionnaire. J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):158-62. doi: 10.1136/jnnp.67.2.158.

  PMID: 10406981 BACKGROUND

• Stuifbergen AK, Blozis SA, Harrison TC, Becker HA. Exercise, functional limitations, and quality of life: A longitudinal study of persons with multiple sclerosis. Arch Phys Med Rehabil. 2006 Jul;87(7):935-43. doi: 10.1016/j.apmr.2006.04.003.

  PMID: 16813781 BACKGROUND

• Trapp BD, Ransohoff R, Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol. 1999 Jun;12(3):295-302. doi: 10.1097/00019052-199906000-00008.

  PMID: 10499174 BACKGROUND

• Tyc F, Boyadjian A. Plasticity of motor cortex induced by coordination and training. Clin Neurophysiol. 2011 Jan;122(1):153-62. doi: 10.1016/j.clinph.2010.05.022. Epub 2010 Jun 17.

  PMID: 21168091 BACKGROUND

• Wolff JR, Joo F, Dames W. Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat. Nature. 1978 Jul 6;274(5666):72-4. doi: 10.1038/274072a0. No abstract available.

  PMID: 661998 BACKGROUND

• Wolff JR, Missler M. Synaptic remodelling and elimination as integral processes of synaptogenesis. APMIS Suppl. 1993;40:9-23.

  PMID: 8311996 BACKGROUND

• Yaka R, Biegon A, Grigoriadis N, Simeonidou C, Grigoriadis S, Alexandrovich AG, Matzner H, Schumann J, Trembovler V, Tsenter J, Shohami E. D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury. FASEB J. 2007 Jul;21(9):2033-41. doi: 10.1096/fj.06-7856com. Epub 2007 Mar 9.

  PMID: 17351125 BACKGROUND

• Zepeda A, Aguilar-Arredondo A, Michel G, Ramos-Languren LE, Escobar ML, Arias C. Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat. Brain Struct Funct. 2013 Mar;218(2):437-53. doi: 10.1007/s00429-012-0407-4. Epub 2012 Apr 6.

  PMID: 22481229 BACKGROUND

• Ziemann U, Ilic TV, Pauli C, Meintzschel F, Ruge D. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex. J Neurosci. 2004 Feb 18;24(7):1666-72. doi: 10.1523/JNEUROSCI.5016-03.2004.

  PMID: 14973238 BACKGROUND

MeSH Terms

Conditions

Brain Injuries

Interventions

D-Aspartic Acid; Exercise Therapy; Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Aspartic Acid; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 25, 2017
• Study Start: November 22, 2017
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2022
• Last Updated: March 15, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)