A Randomized Double-Blinded Placebo-Controlled Exploratory Study of Intravenous Immunoglobulin (NewGam 10%) in Amnestic Mild Cognitive Impairment
Overview
- Phase
- Phase 2
- Intervention
- NewGam 10% IVIG
- Conditions
- Mild Cognitive Impairment
- Sponsor
- Sutter Health
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Shawn Kile, M.D.
MD
Sutter Health
Eligibility Criteria
Inclusion Criteria
- •Age from 50 to \< 85 years old.
- •Diagnosis of Mild Cognitive Impairment, Amnestic type (single or multi domain) according to Petersen criteria (Appendix B) and supported by a CDR score of 0.
- •Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
- •Rosen Modified Hachinski Ischemic score ≤
- •Willing to consent to Apolipoprotein E (ApoE) testing and agree to disclose Apolipoprotein E4 (ApoE4) status. Previous ApoE testing will be accepted.
- •Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening.
- •Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits for two years or the duration of the study.
- •The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years; agrees to have at least 2 separate communications with the study participant per month for the duration of the study (one of these communications must be in person); and attends and completes the CDR interview at 8 study visits along with the subject.
- •Fluency in English and evidence of adequate premorbid intellectual functioning.
- •Adequate manual dexterity, visual, and auditory abilities to perform all aspects of the cognitive and functional assessments.
Exclusion Criteria
- Not provided
Arms & Interventions
intravenous immunoglobulin (IVIG)
IVIG (NewGam 10%)at 0.4 g/kg
Intervention: NewGam 10% IVIG
Saline solution
0.9% saline solution
Intervention: Placebo
Outcomes
Primary Outcomes
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
Time Frame: Baseline, 12, and 24 month MRI evaluation
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.
Secondary Outcomes
- Mean Cognitive Performance at 12 Months(12 months)
- Mean Cognitive Performance at 24 Months(24 month)
- Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)(Baseline to 24 months)
- Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature(Baseline to 24 months following infusion)