Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment
Information source: Sutter Health
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mild Cognitive Impairment
Intervention: NewGam 10% IVIG (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Sutter Health Official(s) and/or principal investigator(s):
Shawn Kile, M.D., Principal Investigator, Affiliation: Sutter Health
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.
Clinical Details
Official title: A Randomized Double-Blinded Placebo-Controlled Exploratory Study of Intravenous Immunoglobulin (NewGam 10%) in Amnestic Mild Cognitive Impairment
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Change in ventricular volumetric as measured by MRI
Secondary outcome: Conversion from amnestic mild cognitive impairment (a-MCI) to Alzheimer Disease (AD)Change in ventricular volume in patients with positive cerebrospinal fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer signature Change in cognitive performance
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).
Eligibility
Minimum age: 50 Years.
Maximum age: 84 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Age from 50 to < 85 years old.
2. 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.
3. Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
4. Rosen Modified Hachinski Ischemic score ≤ 4.
5. Willing to consent to Apolipoprotein E (ApoE) testing and agree to disclose
Apolipoprotein E4 (ApoE4) status. Previous ApoE testing will be accepted.
6. Receiving stable doses of medication(s) for the treatment of non-excluded medical
condition(s) for at least 30 days prior to screening.
7. 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.
8. 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.
9. Fluency in English and evidence of adequate premorbid intellectual functioning.
10. Adequate manual dexterity, visual, and auditory abilities to perform all aspects of
the cognitive and functional assessments.
11. Venous access suitable for repeated infusion and phlebotomy.
Exclusion criteria:
1. Has significant neurological disease, other than a-MCI that may affect cognition.
2. History of clinically evident stroke or history of clinically significant carotid or
vertebrobasilar stenosis or plaque.
3. History of seizures, excluding febrile seizures in childhood.
4. Brain MRI shows moderate or severe cortical or hippocampal atrophy.
5. 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.
6. 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).
7. History of cancer within the last 5 years, with the exception of nonmetastatic basal
cell carcinoma, and squamous cell carcinoma of the skin.
8. Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting).
9. History or evidence of any clinically significant autoimmune disease or disorder of
the immune system (eg., Crohn's Disease, Rheumatoid Arthritis)
10. Women of childbearing potential.
11. Weight greater than 120 kg (264 lbs).
12. Excessive smoking defined as more than 20 cigarettes per day.
13. History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within
the last 2 years.
14. Severe liver or kidney disease verified by the PI review of alanine aminotransferase
(ALT), aspartate aminotransferase (AST) and creatinine.
15. Known coagulopathy, thrombosis, or low platelet count.
16. Known deficiency to Immunoglobulin A (IgA).
17. Positive serology for Hepatitis B or C, or HIV.
18. Concurrent or prior treatment with cholinesterase inhibitors and/or memantine, or
Axona for cognitive enhancement. Exceptions (e. g. brief exposure to one of these
medications) may be authorized if agreed upon by PI and sub-I.
19. Concurrent use of anticholinergic drugs including diphenhydramine.
20. Current use of anticonvulsant drugs for seizures, antiparkinson drugs, anticoagulant
medications (except the use of aspirin 325 mg/day or less, plavix, aggrenox, and
persantine but not for stroke).
21. Concurrent use of opioid pain relievers and related synthetic derivatives.
22. Use of experimental medications for AD or any other investigational medications or
devices within 60 days prior to screening or within 5 half-lives of use of such a
medication prior to screening, whichever is longer.
23. Prior treatment with IVIG or other experimental immunotherapeutic or vaccine for MCI
or AD, or prior treatment with a biological product for the treatment of a-MCI or AD.
Locations and Contacts
Sutter Neuroscience Medical Group, Sacramento, California 95816, United States
Additional Information
Related publications: 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.
Starting date: January 2011
Last updated: August 21, 2014
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