Trial Outcomes & Findings for Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment (NCT NCT01300728)
NCT ID: NCT01300728
Last Updated: 2022-10-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Baseline, 12, and 24 month MRI evaluation
Results posted on
2022-10-27
Participant Flow
Fifty-two participants were randomized; however, 2 participants in the IVIG group did not complete the series of 5 infusions, and 1 placebo participant was excluded due to significant language symptoms which were a barrier to cognitive testing. This resulted having a data set consisting of a total of 49 subjects.
Participant milestones
| Measure |
Intravenous Immunoglobulin (IVIG)
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
0.9% saline solution
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.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
26
|
|
Overall Study
COMPLETED
|
24
|
25
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Intravenous Immunoglobulin (IVIG)
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
0.9% saline solution
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment
Baseline characteristics by cohort
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 Participants
0.9% saline solution
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.
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
72.26 years
STANDARD_DEVIATION 7.91 • n=5 Participants
|
72.40 years
STANDARD_DEVIATION 7.36 • n=7 Participants
|
72.32 years
STANDARD_DEVIATION 7.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Mean Cognitive Performance
MMSE
|
26.75 units on a scale
STANDARD_DEVIATION 2.15 • n=5 Participants
|
26.44 units on a scale
STANDARD_DEVIATION 2.6 • n=7 Participants
|
26.59 units on a scale
STANDARD_DEVIATION 2.37 • n=5 Participants
|
|
Mean Cognitive Performance
ADAS-cog
|
10.63 units on a scale
STANDARD_DEVIATION 4.23 • n=5 Participants
|
10.29 units on a scale
STANDARD_DEVIATION 5.68 • n=7 Participants
|
10.46 units on a scale
STANDARD_DEVIATION 4.97 • n=5 Participants
|
|
Mean Cognitive Performance
CDR_SB
|
1.96 units on a scale
STANDARD_DEVIATION 0.95 • n=5 Participants
|
1.58 units on a scale
STANDARD_DEVIATION 0.90 • n=7 Participants
|
1.78 units on a scale
STANDARD_DEVIATION 0.94 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 12, and 24 month MRI evaluationPopulation: Annualized Percent Change in ventricular volume (APCV) at 12 and 24 months was computed as: ((12 or 24 month volume) - (Baseline volume))/(Baseline volume)/(Time (years) between Baseline and 12 or 24 month visit)
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.
Outcome measures
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 Participants
0.9% saline solution
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.
|
|---|---|---|
|
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
APCV Baseline to12 months
|
5.87 percent change per participant year
Standard Deviation 3.91
|
8.14 percent change per participant year
Standard Deviation 4.43
|
|
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
APCV Baseline to 24 months
|
6.26 percent change per participant year
Standard Deviation 4.17
|
7.08 percent change per participant year
Standard Deviation 4.05
|
SECONDARY outcome
Timeframe: Baseline to 24 monthsThe 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.
Outcome measures
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 Participants
0.9% saline solution
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.
|
|---|---|---|
|
Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)
|
16 participants
|
10 participants
|
SECONDARY outcome
Timeframe: Baseline to 24 months following infusionMean ventricular volume (cubic centimeters) in patients with positive cerebrospinal fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer signature at 24 months following infusion
Outcome measures
| Measure |
Intravenous Immunoglobulin (IVIG)
n=16 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=15 Participants
0.9% saline solution
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.
|
|---|---|---|
|
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
Aβ42 (cc)
|
294.00 cubic centimeters (cc)
Standard Deviation 96.55
|
353.41 cubic centimeters (cc)
Standard Deviation 112.99
|
|
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
tau (cc)
|
107.47 cubic centimeters (cc)
Standard Deviation 58.65
|
96.18 cubic centimeters (cc)
Standard Deviation 65.47
|
|
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
p-tau (cc)
|
43.59 cubic centimeters (cc)
Standard Deviation 19.90
|
39.47 cubic centimeters (cc)
Standard Deviation 30.27
|
SECONDARY outcome
Timeframe: 12 months12 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
Outcome measures
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 Participants
0.9% saline solution
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.
|
|---|---|---|
|
Mean Cognitive Performance at 12 Months
Mini Mental State Exam (MMSE)
|
26.04 units on a scale
Standard Deviation 3.76
|
25.38 units on a scale
Standard Deviation 4.28
|
|
Mean Cognitive Performance at 12 Months
Alzheimer's Disease Assessment Scale (ADAS-Cog)
|
11.03 units on a scale
Standard Deviation 6.66
|
11.00 units on a scale
Standard Deviation 9.14
|
|
Mean Cognitive Performance at 12 Months
Clinical Dementia Rating Sum of Boxes (CDR-SB)
|
2.7 units on a scale
Standard Deviation 1.63
|
2.65 units on a scale
Standard Deviation 2.13
|
SECONDARY outcome
Timeframe: 24 month24 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
Outcome measures
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 Participants
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 Participants
0.9% saline solution
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.
|
|---|---|---|
|
Mean Cognitive Performance at 24 Months
Mini Mental State Exam (MMSE)
|
24.00 units on a scale
Standard Deviation 4.91
|
24.46 units on a scale
Standard Deviation 4.79
|
|
Mean Cognitive Performance at 24 Months
Alzheimer's Disease Assessment Scale (ADAS-Cog)
|
15.39 units on a scale
Standard Deviation 10.55
|
13.25 units on a scale
Standard Deviation 11.77
|
|
Mean Cognitive Performance at 24 Months
Clinical Dementia Rating Sum of Boxes (CDR-SB)
|
4.33 units on a scale
Standard Deviation 3.48
|
3.37 units on a scale
Standard Deviation 2.73
|
Adverse Events
Intravenous Immunoglobulin (IVIG)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Saline Solution
Serious events: 0 serious events
Other events: 2 other events
Deaths: 2 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intravenous Immunoglobulin (IVIG)
n=24 participants at risk
IVIG (NewGam 10%)at 0.4 g/kg
NewGam 10% IVIG: 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.
|
Saline Solution
n=25 participants at risk
0.9% saline solution
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.
|
|---|---|---|
|
General disorders
Insomnia
|
4.2%
1/24 • Number of events 1 • 2 years
|
0.00%
0/25 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
4.2%
1/24 • Number of events 1 • 2 years
|
0.00%
0/25 • 2 years
|
|
General disorders
Low grade fever
|
4.2%
1/24 • Number of events 1 • 2 years
|
0.00%
0/25 • 2 years
|
|
General disorders
Headache
|
4.2%
1/24 • Number of events 1 • 2 years
|
0.00%
0/25 • 2 years
|
|
General disorders
Chills
|
0.00%
0/24 • 2 years
|
4.0%
1/25 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Emesis
|
0.00%
0/24 • 2 years
|
4.0%
1/25 • Number of events 1 • 2 years
|
|
General disorders
Fatigue
|
0.00%
0/24 • 2 years
|
4.0%
1/25 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Decreased appetite
|
0.00%
0/24 • 2 years
|
4.0%
1/25 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/24 • 2 years
|
4.0%
1/25 • Number of events 1 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place