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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Memantine; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Melody Hackett, BS; Phone Number: 313-966-0473; Email: mgilroy@med.wayne.edu

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Wayne State University
      • Contact: Melody Hackett, BS; Phone Number: 313-966-0473; Email: mgilroy@med.wayne.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Memantine; 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.	Drug: Memantine; 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.; Other Names: Namenda
Placebo Comparator: Placebo; 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.	Other: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from baseline RAVLT at year 1
Change in Trail test performance time (baseline to year-1)	Investigate the effects of Memantine administration on visual attention and task switching	Change from baseline Trail test at year 1
Change in Stroop Color Word Test performance (baseline to year-1)	Investigate the effects of Memantine administration on cognitive interference and processing speed	Change from baseline Stroop Color Word Test at year 1
Change Judgment of Line Orientation test performance score (baseline to year-1)	Investigate the effects of Memantine administration on visuospatial skills	Change from baseline Judgment of Line Orientation test at year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from baseline to year-1 of ICV for each brain region mentioned above.
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 from baseline to year-1 of MK for each brain region mentioned above.
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 from baseline to year-1 of Cth for each brain region mentioned above.
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 )	Change from baseline to year-1 of FA for each brain region mentioned above.

Collaborators and Investigators

• Sponsor: Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 09282018

Drug and device information, study documents

• 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