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Study of Memantine for Gait Disorders And Attention Deficit In Parkinson's Disease (FOGG-I)

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ClinicalTrials.gov Identifier: NCT01108029
Recruitment Status : Completed
First Posted : April 21, 2010
Last Update Posted : March 26, 2012
Information provided by (Responsible Party):
University Hospital, Lille

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Gait Disorders, Neurologic Drug: memantine Drug: placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of Memantine to Treat Gait Disorders And Attention Deficit In Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Monocentric Trial
Study Start Date : October 2009
Actual Primary Completion Date : September 2010
Actual Study Completion Date : October 2010

Arm Intervention/treatment
Active Comparator: memantine
memantine 20 mg/day (2 tablets 1 time a day in the morning)
Drug: memantine
2 tablets of 10 mg of memantine 1 time a day in the morning
Other Name: EBIXA

Placebo Comparator: placebo
2 tablets (1 time a day in the morning) during 3 months
Drug: placebo
2 tablets of placebo 1 time a day in the morning

Primary Outcome Measures :
  1. stride length by gait analysis with an optoelectronic system (VICON®) [ Time Frame: 3 months of treatment ]

Secondary Outcome Measures :
  1. 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®) [ Time Frame: 3 months ]
  2. Gait and motor symptoms: the "Freezing Of Gait trajectory",the UPDRS motor score (part III), the dyskinesia rating scale, [ Time Frame: 3 months ]
  3. Attention: simple and complex reactions times [ Time Frame: 3 months ]
  4. hypertonia of axial flexor and extensor [ Time Frame: 3 months ]
    hypertonia of axial flexor and extensor measured on mean and total work at 30°/s (Joules) by passive flexion and extension on isokinetic dynamometer (Cybex 6000)

  5. Drowsiness: Epworth and Parkinson's disease Sleep Scales [ Time Frame: 3 months ]
  6. Apathy Lille Apathy Rating Scale [ Time Frame: 3 months ]
  7. Depression: MADRS [ Time Frame: 3 months ]
  8. Safety and Tolerability Endpoints [ Time Frame: 3 months ]
    • Safety : Recording of all serious and non serious adverse events reported by the patients, electrocardiogram, blood pressure and biological analyzes (blood counts, ionogramme, urea, creatinemia, transaminases, alkaline phosphatase, bilirubinemia, gamma GT, magnesium)
    • Tolerability Number of subjects (%) who discontinue the study Number of subjects (%) who discontinue the study due to AEs Safety Measures AE incidence Safety laboratory values Vital signs Blood pressure monitoring ECG Physical and neurological examination

  9. strength of axial flexor and extensor [ Time Frame: 3 months ]
    strength of axial flexor and extensor measured on mean and total work of 3 repetitions at 30°/s (Joules) and of 5 repetitions at 120°/s (Joules) by active flexion and extension on isokinetic dynamometer

  10. DaT scan [ Time Frame: 3 months ]
    The inhibition of the presynaptic dopamine transporter by memantine was assessed by the mean DAT density of the bilateral striatum (putamen and caudate nuclei) using [99mTc]TRODAT-1 SPECT before and after 3 months of treatment.

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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): NCT01108029

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Lille, France, 59037
Sponsors and Collaborators
University Hospital, Lille
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Principal Investigator: David Devos, MD, PhD Department of Neurology, University Hospital of Lille
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01108029    
Other Study ID Numbers: 2008-008210-38
2008_02/0841 ( Other Identifier: sponsor )
First Posted: April 21, 2010    Key Record Dates
Last Update Posted: March 26, 2012
Last Verified: July 2009
Keywords provided by University Hospital, Lille:
Parkinson's disease
Freezing of Gait
NMDA receptor
No Dementia
Additional relevant MeSH terms:
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Parkinson Disease
Nervous System Diseases
Gait Disorders, Neurologic
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurologic Manifestations
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents