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Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment (MCI)

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ClinicalTrials.gov Identifier: NCT01300728
Recruitment Status : Active, not recruiting
First Posted : February 23, 2011
Results First Posted : March 31, 2016
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Shawn Kile, M.D., Sutter Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Mild Cognitive Impairment
Interventions Drug: NewGam 10% IVIG
Other: Placebo
Enrollment 52
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 26 26
Completed 24 25
Not Completed 2 1
Reason Not Completed
Withdrawal by Subject             1             1
Physician Decision             1             0
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 24 25 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 25 participants 49 participants
72.26  (7.91) 72.40  (7.36) 72.32  (7.56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 25 participants 49 participants
Female
14
  58.3%
14
  56.0%
28
  57.1%
Male
10
  41.7%
11
  44.0%
21
  42.9%
Mean Cognitive Performance   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 24 participants 25 participants 49 participants
MMSE 26.75  (2.15) 26.44  (2.6) 26.59  (2.37)
ADAS-cog 10.63  (4.23) 10.29  (5.68) 10.46  (4.97)
CDR_SB 1.96  (0.95) 1.58  (0.90) 1.78  (0.94)
[1]
Measure Description:

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
1.Primary Outcome
Title Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description

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)

Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 24 25
Mean (Standard Deviation)
Unit of Measure: percent change per participant year
APCV Baseline to12 months 5.87  (3.91) 8.14  (4.43)
APCV Baseline to 24 months 6.26  (4.17) 7.08  (4.05)
2.Secondary Outcome
Title Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 24 25
Measure Type: Number
Unit of Measure: participants
16 10
3.Secondary Outcome
Title Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: cubic centimeters (cc)
Aβ42 (cc) 294.00  (96.55) 353.41  (112.99)
tau (cc) 107.47  (58.65) 96.18  (65.47)
p-tau (cc) 43.59  (19.90) 39.47  (30.27)
4.Secondary Outcome
Title Mean Cognitive Performance at 12 Months
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 24 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
Mini Mental State Exam (MMSE) 26.04  (3.76) 25.38  (4.28)
Alzheimer's Disease Assessment Scale (ADAS-Cog) 11.03  (6.66) 11.00  (9.14)
Clinical Dementia Rating Sum of Boxes (CDR-SB) 2.7  (1.63) 2.65  (2.13)
5.Secondary Outcome
Title Mean Cognitive Performance at 24 Months
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 24 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
Mini Mental State Exam (MMSE) 24.00  (4.91) 24.46  (4.79)
Alzheimer's Disease Assessment Scale (ADAS-Cog) 15.39  (10.55) 13.25  (11.77)
Clinical Dementia Rating Sum of Boxes (CDR-SB) 4.33  (3.48) 3.37  (2.73)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intravenous Immunoglobulin (IVIG) Saline Solution
Hide Arm/Group Description

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.

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.

All-Cause Mortality
Intravenous Immunoglobulin (IVIG) Saline Solution
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Intravenous Immunoglobulin (IVIG) Saline Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/25 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Intravenous Immunoglobulin (IVIG) Saline Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/24 (4.17%)      2/25 (8.00%)    
Gastrointestinal disorders     
Nausea [1]  1/24 (4.17%)  1 0/25 (0.00%)  0
Emesis [1]  0/24 (0.00%)  0 1/25 (4.00%)  1
Decreased appetite [1]  0/24 (0.00%)  0 1/25 (4.00%)  1
General disorders     
Insomnia [1]  1/24 (4.17%)  1 0/25 (0.00%)  0
Low grade fever [1]  1/24 (4.17%)  1 0/25 (0.00%)  0
Headache [2]  1/24 (4.17%)  1 0/25 (0.00%)  0
Chills [2]  0/24 (0.00%)  0 1/25 (4.00%)  1
Fatigue [1]  0/24 (0.00%)  0 1/25 (4.00%)  1
Skin and subcutaneous tissue disorders     
Rash [1]  0/24 (0.00%)  0 1/25 (4.00%)  1
[1]
Severity = mild
[2]
Severity = moderate
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Shawn Kile, MD
Organization: Sutter Neurology Medical Group
Phone: (916) 454-6850
EMail: KileS@sutterhealth.org
Layout table for additonal information
Responsible Party: Shawn Kile, M.D., Sutter Health
ClinicalTrials.gov Identifier: NCT01300728     History of Changes
Other Study ID Numbers: IVIG-KILE-032010
First Submitted: February 22, 2011
First Posted: February 23, 2011
Results First Submitted: August 8, 2015
Results First Posted: March 31, 2016
Last Update Posted: October 8, 2019