Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment

NCT01300728 | Completed Phase 2 Results DMC

• 1 other identifier: IVIG-KILE-032010
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Keywords

Intravenous immunotherapy; Conversion to Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 12, and 24 month MRI evaluation

Secondary Outcomes (4)

• 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

• Mean Cognitive Performance at 12 Months

  12 months

• Mean Cognitive Performance at 24 Months

  24 month

Study Arms (2)

intravenous immunoglobulin (IVIG)

EXPERIMENTAL

IVIG (NewGam 10%)at 0.4 g/kg

Drug: NewGam 10% IVIG

Saline solution

PLACEBO COMPARATOR

0.9% saline solution

Other: Placebo

Interventions

NewGam 10% IVIG DRUG

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.

intravenous immunoglobulin (IVIG)

Placebo OTHER

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.

Saline solution

Eligibility Criteria

• Age: 50 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0.5.
• Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
• Rosen Modified Hachinski Ischemic score ≤ 4.
• 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.
• Venous access suitable for repeated infusion and phlebotomy.

You may not qualify if:

• Has significant neurological disease, other than a-MCI that may affect cognition.
• History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque.
• History of seizures, excluding febrile seizures in childhood.
• Brain MRI shows moderate or severe cortical or hippocampal atrophy.
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, CSF shunts, claustrophobia, metal fragments or foreign objects in the eyes, skin, or body that would contraindicate a brain MRI scan.
• Current presence of a clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR).
• History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma, and squamous cell carcinoma of the skin.
• Uncontrolled hypertension (diastolic BP\> 100 mmHg or systolic BP\> 160 mmHg, sitting).
• History or evidence of any clinically significant autoimmune disease or disorder of the immune system (eg., Crohn's Disease, Rheumatoid Arthritis)
• Women of childbearing potential.
• Weight greater than 120 kg (264 lbs).
• Excessive smoking defined as more than 20 cigarettes per day.
• History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within the last 2 years.
• Severe liver or kidney disease verified by the PI review of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine.
• Known coagulopathy, thrombosis, or low platelet count.

Sponsors & Collaborators

• Sutter Health: lead

Study Sites (1)

Sutter Neuroscience Medical Group

Sacramento, California, 95816, United States

Location

Related Publications (3)

• Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009 Nov;30(11):1728-36. doi: 10.1016/j.neurobiolaging.2007.12.021. Epub 2008 Feb 21.

  PMID: 18294736 BACKGROUND

• Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Chan M, Ghassemi A. IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia. J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):106-112. doi: 10.1136/jnnp-2015-311486. Epub 2015 Sep 29.

  PMID: 26420886 RESULT

• Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Au Y, Chan M, Ghassemi A. Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease. BMC Neurosci. 2021 Aug 6;22(1):49. doi: 10.1186/s12868-021-00651-2.

  PMID: 34362303 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Shawn Kile, MD
• Organization: Sutter Neurology Medical Group

KileS@sutterhealth.org

(916) 454-6850

Study Officials

• Shawn Kile, M.D.

  Sutter Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 22, 2011
• First Posted: February 23, 2011
• Study Start: January 1, 2011
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: October 27, 2022
• Results First Posted: March 31, 2016

Record last verified: 2022-07

Locations

US (1)