Patients with mild cognitive impairment (MCI) are a group recognized at being at high risk of progressing to Alzheimer disease. Treatment of MCI with immunotherapy with intravenous immunoglobulins (IVIG) could potentially reduce the risk of progression to Alzheimer disease. This study will evaluate the efficacy of intravenous immunoglobulin in patients with MCI over 24 months after the first infusion. This study will also document conversion from MCI to Alzheimer's Disease.
Screening procedures at visit 1 will take place up to 28 days prior to Visit 2 (Day 1) dosing. Screening labs and assessments will be performed during the screening period. A brain MRI will be obtained as standard of care within 6 months prior to the screening period. The first dose of study drug is administered on Day 1. Visits 2 through 6 have a ±1 day window and occur every 14 days over two months. The investigator will determine if a subject is suitable to continue following the missed infusion. Visits 7 through 12 (Month 4 through Month 24) have a ±7 day window. All study screening data from Visit 1 including laboratory results must be reviewed for study eligibility prior to receiving first dose of study drug. Visit 2 physical exams and neurological exams prior to infusion may occur within 72 hours prior to the first infusion. Prior to infusion, a review of concomitant medications and adverse events takes place to ensure that no excluded medications have been added or medication discontinued or dose changed that were required to have been stable. If the subject continues to be eligible for enrollment, the subject will be randomized, infused with study medication and will remain in the infusion clinic for at least 4 hours following the start of the infusion for safety assessments on Visit 2 (Day 1).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
52
Subjects will be randomized to receive either an infusion of IVIG at 0.4 g/kg or every 14 days for two months for a total of five infusions. Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. Twenty-five subjects will receive IVIG and 25 subjects will receive placebo.
Subjects will be randomized to receive either an infusion of 0.9% saline solution (placebo) every 14 days for two months for a total of five infusions. Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio.
Sutter Neuroscience Medical Group
Sacramento, California, United States
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
Change in ventricular volumetric as measured by MRI at baseline, 12, and 24 months following the first infusion of either 0.4 g/kg NewGam or 0.9% saline solution(placebo) every 14 days x 5. Participants will also be classified as early MCI (EMCI) if baseline CDR-SB is less than 1.5, and late MCI (LMCI) if CDR-SB is greater than or equal to 1.5.
Time frame: Baseline, 12, and 24 month MRI evaluation
Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)
The National Institute of Neurological and Communicative Disorders and Stroke - Alzheimers Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer's Criteria were proposed in 1984 by NINCDS-ADRDA criteria for diagnosing Alzheimer Disease and Clinical Dementia Rating (CDR) will be used to determine conversion from a-MCI to AD.
Time frame: Baseline to 24 months
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
Mean ventricular volume (cubic centimeters) in patients with positive cerebrospinal fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer signature at 24 months following infusion
Time frame: Baseline to 24 months following infusion
Mean Cognitive Performance at 12 Months
12 month cognitive performance in treatment (IVIG/placebo) is measured by: * Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) * Scale from 0 to 85 (0 is best cognitive performance) * Score is the sum of 12 sub-scales. * Mini Mental State Exam (MMSE) * Scale from 0 to 30 (30 is best cognitive performance) * Score is the sum of 11 sub-scales. * Clinical Dementia Rating - Sum of Boxes (CDR-SB) * Scale is 0 to 18 (0 is best cognitive performance) * Score is the sum of 6 sub-scales
Time frame: 12 months
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Mean Cognitive Performance at 24 Months
24 month cognitive performance in treatment (IVIG/placebo) is measured by: * Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) * Scale from 0 to 85 (0 is best cognitive performance) * Score is the sum of 12 sub-scales. * Mini Mental State Exam (MMSE) * Scale from 0 to 30 (30 is best cognitive performance) * Score is the sum of 11 sub-scales. * Clinical Dementia Rating - Sum of Boxes (CDR-SB) * Scale is 0 to 18 (0 is best cognitive performance) * Score is the sum of 6 sub-scales
Time frame: 24 month