Study of Memantine for Gait Disorders And Attention Deficit In Parkinson's Disease

NCT01108029 | Completed Phase 4 DMC

• 2 other identifiers: 2008-008210-382008_02/0841
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Along with cognitive and psychobehavioural disorders, gait disorders represent a major problem in the treatment of advanced Parkinson's disease (PD). PD can be considered to be a hyperglutamatergic disease because dopaminergic depletion induces hyperactivity of the subthalamic nucleus (STN) and the internal pallidum (GPi), with glutamatergic hyperactivity of the STN's efferent pathway, i.e., the subthalamopallidal, subthalamonigral and subthalamo-entopeduncular pathways (projecting to the pedunculopontine nucleus (PPN)). Excess glutamate in the PPN has also been observed in the 6-OHDA rat model of PD. Reduction of this glutamatergic hyperactivity within the PPN via the systemic or intra-peduncular administration of glutamate antagonists improves akinesia in drug-induced murine and primate models of PD, via the NMDA and AMPA receptors. High doses of memantine (10 mg/kg) improve locomotion in reserpine- and alpha-methyl-p-tyrosine-treated rats. In humans, the PPN may play a key role in gait, posture control, axial rigidity and attention. It is also involved in the gating of sensory information involved in the startle reflex, which can be studied via prepulse inhibition (PPI) of the blink reflex. At present, two uncompetitive NMDA receptor antagonists are approved for use in humans: amantadine and memantine. Reviews of the recent literature on these drugs have identified no published studies specifically on severe gait and attention disorders in PD. Memantine is a partial blocker of open NMDA channels. The value of memantine relates to the fact that it decreases excessive glutamatergic transmission by lowering the synaptic noise due to excessive activation of NMDA receptors. In this double-blind study, the investigators shall seek to demonstrate the presence or absence of an effect of memantine on gait and attention disorders. In order to study the interaction between glutamatergic hyperactivity and the dopaminergic system, the investigators shall study the phenomena both in the absence of L-dopa and following acute administration of the latter. Twenty eight volunteer, non-demented, late-stage PD patients displaying severe gait disorders will receive memantine (20 mg/day) or placebo for 3 months. The investigators expect to see a reduction in gait and attention disorders, together with an improvement in the blink reflex with PPI under memantine. This pilot study could subsequently be turned into a double-blind, placebo-controlled multicenter study.

Conditions

Parkinson's Disease; Gait Disorders, Neurologic

Keywords

Parkinson's disease; Freezing of Gait; Memantine; NMDA receptor; glutamate; No Dementia

Outcome Measures

Primary Outcomes (1)

• stride length by gait analysis with an optoelectronic system (VICON®)

  3 months of treatment

Secondary Outcomes (10)

• Kinematic and Kinetic parameters (stride length, stride time, velocity, cadence and variability of these parameters) of the gait initiation and the stabilised gait using the optoelectronic system (VICON®)

  3 months

• Gait and motor symptoms: the "Freezing Of Gait trajectory",the UPDRS motor score (part III), the dyskinesia rating scale,

  3 months

• Attention: simple and complex reactions times

  3 months

• hypertonia of axial flexor and extensor

  3 months

• Drowsiness: Epworth and Parkinson's disease Sleep Scales

  3 months

Study Arms (2)

memantine

ACTIVE COMPARATOR

memantine 20 mg/day (2 tablets 1 time a day in the morning)

Drug: memantine

placebo

PLACEBO COMPARATOR

2 tablets (1 time a day in the morning) during 3 months

Drug: placebo

Interventions

memantine DRUG

2 tablets of 10 mg of memantine 1 time a day in the morning

Also known as: EBIXA

memantine

placebo DRUG

2 tablets of placebo 1 time a day in the morning

placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson's disease of more than 5 years
• Subthalamic nucleus stimulation
• Gait disorders impeding moderately to severely the activities of daily living
• gait disorders including freezing of gait
• able to walk without physical assistance

You may not qualify if:

• Dementia (MMSE \< 27 et score de Mattis \< 130)
• Requiring dopatherapy modification
• Requiring subthalamic stimulation parameters adaptation
• Psychiatric disorders: hallucinations, unstable thymic disorders, psychosis)
• Cardiac disorders: dysrhythmia or unstable arterial hypertension
• Unstable or severe medical illness
• intolerance or contraindication to memantine

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Devos

Lille, 59037, France

Location

Related Publications (1)

• Moreau C, Delval A, Tiffreau V, Defebvre L, Dujardin K, Duhamel A, Petyt G, Hossein-Foucher C, Blum D, Sablonniere B, Schraen S, Allorge D, Destee A, Bordet R, Devos D. Memantine for axial signs in Parkinson's disease: a randomised, double-blind, placebo-controlled pilot study. J Neurol Neurosurg Psychiatry. 2013 May;84(5):552-5. doi: 10.1136/jnnp-2012-303182. Epub 2012 Oct 16.

  PMID: 23077087 RESULT

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic

Interventions

Memantine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• David Devos, MD, PhD

  Department of Neurology, University Hospital of Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2009
• First Posted: April 21, 2010
• Study Start: October 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: October 1, 2010
• Last Updated: May 14, 2026

Record last verified: 2009-07

Locations

FR (1)