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Inhibition of α-synuclein Cell-cell Transmission by NMDAR Blocker, Memantine

Primary Purpose

Parkinson Disease

Status
Unknown status
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
Wayne State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Diagnosed with idiopathic PD for at least 2 or more years
  2. 45 to 85 years of age
  3. Have been on stable doses of anti-Parkinson medication
  4. Able to give informed consent
  5. Able to undergo brain MRI
  6. Unilateral symptoms
  7. A score of 26 or greater on the Montreal Cognitive Assessment (MOCA), a measure of a patients short-term memory recall, the ability to determine visual-spatial relationships of objects, attention, concentration, working memory, language and orientation to time and place
  8. Use of one method of medically approved contraceptive

Exclusion Criteria:

  1. History of any surgical intervention for treating PD (i.e. deep brain stimulation)
  2. Extreme physical disability
  3. History or current diagnosis of unstable psychiatric condition
  4. Presence of dementia or any other condition that prevents the ability of the participant to provide fully informed consent
  5. Other brain disease
  6. Treatment with Memantine 30 days prior to baseline
  7. Females who are pregnant or nursing
  8. Presence of interacting medications with Memantine or co-morbid medical conditions that may be exacerbated by this agent
  9. Moderately significant drug interactions with Dextromethorphan, Amantadine, Sodium Bicarbonate, and Acetazolamide
  10. Previous Allergic reaction to Memantine
  11. Any genetic form of PD

Sites / Locations

  • Wayne State UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Memantine

Placebo

Arm Description

Memantine will be started at 10 mg tablet once/day for a week at bedtime. After one week Memantine will be administered at 10 mg tablet twice/day for 51 weeks.

Placebo will be started at 10 mg tablet once/day for a week at bedtime. After one week placebo will be administered at 10 mg tablet twice/day for 51 weeks.

Outcomes

Primary Outcome Measures

Change in Rey Auditory Verbal Learning Test (RAVLT) Scores (baseline to year-1)
Investigate the effects of Memantine administration on the global cognitive status and executive function
Change in Trail test performance time (baseline to year-1)
Investigate the effects of Memantine administration on visual attention and task switching
Change in Stroop Color Word Test performance (baseline to year-1)
Investigate the effects of Memantine administration on cognitive interference and processing speed
Change Judgment of Line Orientation test performance score (baseline to year-1)
Investigate the effects of Memantine administration on visuospatial skills

Secondary Outcome Measures

Change in the Intracellular volume (ICV), as measured by MRI NODDI sequence, in multiple brain regions, baseline to year-1.
ICV component is calculated from the NODDI MRI, using available software, for dorsolateral prefrontal cortex, precuneous, anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, thalamus, caudate, putamen, association visual cortex, and primary visual cortex. The change in ICV fro each region will be calculated from baseline to year-1, and would constitute a regional outcome measure, but due to the number of regions, they have all been described under outcome#5, since they have the same unit of measurement. Group comparisons (i.e. placebo v. memantine for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Change in the mean kurtosis (MK), an index of tissue complexity, as measured by MRI diffusion kurtosis (DKI) sequence sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
MK is calculated from the DKI MRI, using available software, for regions mentioned in outcome #5. The change in MK from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Change in cortical thickness (Cth), as measured by MRI T1 sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
Cth is calculated from T1 MRI, using available software, for regions mentioned in outcome #5. The change in Cth from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine, for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Change in fractional anisotropy (FA), as measured by diffusion tensor imaging (DTI) sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
Utilizing FA to investigate white matter integrity in corpus callosum, inferior longitudinal fasciculus, and corona radiata. The change in FA from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine, for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )

Full Information

First Posted
October 2, 2018
Last Updated
June 29, 2020
Sponsor
Wayne State University
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1. Study Identification

Unique Protocol Identification Number
NCT03858270
Brief Title
Inhibition of α-synuclein Cell-cell Transmission by NMDAR Blocker, Memantine
Official Title
Inhibition of α-synuclein Cell-cell Transmission by NMDAR Blocker, Memantine
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
April 1, 2022 (Anticipated)
Study Completion Date
July 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wayne State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Lewy Body Dementia (LBD), is the second most common form of dementia after Alzheimer's Disease. Dementia is defined as a serious loss in cognitive ability due to damages or disease in the brain beyond what is normal aging. With Lewy Body Dementia, protein deposits, or Lewy Bodies, accumulate in nerve cells throughout the brain, affecting motor control, memory and thinking. LBD can also form with the progression of Parkinson's disease (PD). PD is a degenerative nervous system disorder that affects movement ability. Using more sensitive MRI imaging techniques the investigators are attempting to see if disease progression can be monitored more closely. At the same time, the study medication Memantine will be compared to a placebo to determine if it can be used to slow the progression of PD. The purpose of this study is to assess if disease progression can be better monitored through brain imaging and if Memantine will help slow disease progression.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Memantine
Arm Type
Experimental
Arm Description
Memantine will be started at 10 mg tablet once/day for a week at bedtime. After one week Memantine will be administered at 10 mg tablet twice/day for 51 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be started at 10 mg tablet once/day for a week at bedtime. After one week placebo will be administered at 10 mg tablet twice/day for 51 weeks.
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Namenda
Intervention Description
Memantine will be started at 10 mg tablet once/day for a week at bedtime. After one week Memantine will be administered at 10 mg tablet twice/day for 51 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo will be started at 10 mg tablet once/day for a week at bedtime. After one week Placebo will be administered at 10 mg tablet twice/day for 51 weeks.
Primary Outcome Measure Information:
Title
Change in Rey Auditory Verbal Learning Test (RAVLT) Scores (baseline to year-1)
Description
Investigate the effects of Memantine administration on the global cognitive status and executive function
Time Frame
Change from baseline RAVLT at year 1
Title
Change in Trail test performance time (baseline to year-1)
Description
Investigate the effects of Memantine administration on visual attention and task switching
Time Frame
Change from baseline Trail test at year 1
Title
Change in Stroop Color Word Test performance (baseline to year-1)
Description
Investigate the effects of Memantine administration on cognitive interference and processing speed
Time Frame
Change from baseline Stroop Color Word Test at year 1
Title
Change Judgment of Line Orientation test performance score (baseline to year-1)
Description
Investigate the effects of Memantine administration on visuospatial skills
Time Frame
Change from baseline Judgment of Line Orientation test at year 1
Secondary Outcome Measure Information:
Title
Change in the Intracellular volume (ICV), as measured by MRI NODDI sequence, in multiple brain regions, baseline to year-1.
Description
ICV component is calculated from the NODDI MRI, using available software, for dorsolateral prefrontal cortex, precuneous, anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, thalamus, caudate, putamen, association visual cortex, and primary visual cortex. The change in ICV fro each region will be calculated from baseline to year-1, and would constitute a regional outcome measure, but due to the number of regions, they have all been described under outcome#5, since they have the same unit of measurement. Group comparisons (i.e. placebo v. memantine for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Time Frame
Change from baseline to year-1 of ICV for each brain region mentioned above.
Title
Change in the mean kurtosis (MK), an index of tissue complexity, as measured by MRI diffusion kurtosis (DKI) sequence sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
Description
MK is calculated from the DKI MRI, using available software, for regions mentioned in outcome #5. The change in MK from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Time Frame
Change from baseline to year-1 of MK for each brain region mentioned above.
Title
Change in cortical thickness (Cth), as measured by MRI T1 sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
Description
Cth is calculated from T1 MRI, using available software, for regions mentioned in outcome #5. The change in Cth from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine, for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Time Frame
Change from baseline to year-1 of Cth for each brain region mentioned above.
Title
Change in fractional anisotropy (FA), as measured by diffusion tensor imaging (DTI) sequence, in multiple brain regions (mentioned in outcome #5), baseline to year-1.
Description
Utilizing FA to investigate white matter integrity in corpus callosum, inferior longitudinal fasciculus, and corona radiata. The change in FA from each region will be calculated from baseline to year-1. Group comparisons (i.e. placebo v. memantine, for each region) will be corrected for multiple comparisons as appropriate (E.g Bonferroni )
Time Frame
Change from baseline to year-1 of FA for each brain region mentioned above.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Diagnosed with idiopathic PD for at least 2 or more years 45 to 85 years of age Have been on stable doses of anti-Parkinson medication Able to give informed consent Able to undergo brain MRI Unilateral symptoms A score of 26 or greater on the Montreal Cognitive Assessment (MOCA), a measure of a patients short-term memory recall, the ability to determine visual-spatial relationships of objects, attention, concentration, working memory, language and orientation to time and place Use of one method of medically approved contraceptive Exclusion Criteria: History of any surgical intervention for treating PD (i.e. deep brain stimulation) Extreme physical disability History or current diagnosis of unstable psychiatric condition Presence of dementia or any other condition that prevents the ability of the participant to provide fully informed consent Other brain disease Treatment with Memantine 30 days prior to baseline Females who are pregnant or nursing Presence of interacting medications with Memantine or co-morbid medical conditions that may be exacerbated by this agent Moderately significant drug interactions with Dextromethorphan, Amantadine, Sodium Bicarbonate, and Acetazolamide Previous Allergic reaction to Memantine Any genetic form of PD
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melody Hackett, BS
Phone
313-966-0473
Email
mgilroy@med.wayne.edu
Facility Information:
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melody Hackett, BS
Phone
313-966-0473
Email
mgilroy@med.wayne.edu

12. IPD Sharing Statement

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Inhibition of α-synuclein Cell-cell Transmission by NMDAR Blocker, Memantine

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