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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01108029
First received: July 20, 2009
Last updated: March 23, 2012
Last verified: July 2009
  Purpose

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 Intervention Phase
Parkinson's Disease
Gait Disorders, Neurologic
Drug: memantine
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • stride length by gait analysis with an optoelectronic system (VICON®) [ Time Frame: 3 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Gait and motor symptoms: the "Freezing Of Gait trajectory",the UPDRS motor score (part III), the dyskinesia rating scale, [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Attention: simple and complex reactions times [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • hypertonia of axial flexor and extensor [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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)

  • Drowsiness: Epworth and Parkinson's disease Sleep Scales [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Apathy Lille Apathy Rating Scale [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Depression: MADRS [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Safety and Tolerability Endpoints [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    • 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

  • strength of axial flexor and extensor [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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

  • DaT scan [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 28
Study Start Date: October 2009
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108029

Locations
France
Devos
Lille, France, 59037
Sponsors and Collaborators
University Hospital, Lille
Investigators
Principal Investigator: David Devos, MD, PhD Department of Neurology, University Hospital of Lille
  More Information

No publications provided by University Hospital, Lille

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01108029     History of Changes
Other Study ID Numbers: 2008-008210-38, 2008_02/0841
Study First Received: July 20, 2009
Last Updated: March 23, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
Parkinson's disease
Freezing of Gait
Memantine
NMDA receptor
glutamate
No Dementia

Additional relevant MeSH terms:
Nervous System Diseases
Parkinson Disease
Gait Disorders, Neurologic
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurologic Manifestations
Signs and Symptoms
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014