Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease

NCT03319810 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SIMR_Kile_IVIG POC
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof of concept study to determine if changes in brain amyloid levels are evident three months after infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. Amyloid levels will be measured by Florbetapir PET and retinal scan.

Conditions

Mild Cognitive Impairment

Keywords

MCI, Alzheimer Disease, AD

Outcome Measures

Primary Outcomes (2)

• Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months

  Amyloid deposition in the brain is thought to lead to the development of cognitive decline and conversion to AD. Each participant's amyloid burden can also be quantified through the computation of a Standard Uptake Value ratio (SUVr).

  Baseline to 3 months

• Change in Baseline Retinal Amyloid Imaging (RAI) at 3 Months

  This is a noninvasive imaging technique that can detect amyloid-beta deposition in the retinas of the eye.

  Baseline to 3 months

Study Arms (1)

infusion of IVIG

EXPERIMENTAL

Biological: Octagam 10%

Interventions

Octagam 10% BIOLOGICAL

FDA approved human normal immunoglobulin solution ready for intravenous administration

infusion of IVIG

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 50 to \<85 years.
• Evidence of amyloid pathology on Florbetapir PET at screening.
• Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A)
• MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy and/or bilateral parietal atrophy.
• CDR score of 0.5
• Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
• Rosen Modified Hachinski Ischemic score ≤4.
• Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening. Cholinesterase inhibitors and memantine are allowed if doses have stable been least 30 days prior to screening.
• Agree to refrain from participating in any treatment or clinical trial targeting amyloid for the duration of the study.
• Agree to refrain from taking any herbal supplement considered to enhance cognition unless approved by the investigator for the duration of the study.
• Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits.
• The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years and has had approximately 2 or more separate communications with the study participant per month (at least one of these communications in person).
• 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 infusions and phlebotomy.

You may not qualify if:

• Has significant neurological disease other than MCI that in the opinion of the investigator 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.
• History of screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to multiple microhemorrhages (2 or more), history or evidence of a single prior hemorrhage \> 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a single prior infarct \> 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions of significance as determined by the PI (e.g., arachnoid cysts or brain tumors such as meningioma).
• Brain MRI shows moderate or severe cortical or hippocampal atrophy.
• Sensitivity to Florbetapir.
• Other present/planned ionized radiation that, in combination with planned exposure to PET ligands for this study, would result in cumulative exposure that would exceed recommended limits.
• Ophthalmologic condition that would interfere with retinal amyloid imaging.
• Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) or symptom (e.g., hallucinations) that in the opinion of the investigator could affect the subject's ability to complete the study.
• Current clinically significant systemic illness that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study including but not limited to renal failure or myocardial infarction.
• 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 (e.g., Crohn's Disease, Rheumatoid Arthritis)
• Clinically significant infection within the last 30 days (e.g., chronic persistent or acute infection (eg, upper respiratory infection \[URI\], urinary tract infection \[UTI\]).
• Female subjects of childbearing potential.

Sponsors & Collaborators

• Sutter Health: lead

Study Sites (1)

Sutter Neuroscience Medical Group

Sacramento, California, 95816, United States

Location

Related Publications (1)

• 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 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Limitations and Caveats

Small number of subjects analyzed.

Results Point of Contact

• Title: Carol Parise, PhD, Research Scientist
• Organization: Sutter Institute for Medical Research

PariseC@sutterhealth.org

(916) 887-4744

Study Officials

• Shawn Kile, MD

  Sutter Health

  PRINCIPAL INVESTIGATOR

• Carol Parise, PhD

  Sutter Health

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single center, open label, proof of concept, out-patient study.

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 24, 2017
• Study Start: January 4, 2018
• Primary Completion: July 19, 2018
• Study Completion: July 19, 2018
• Last Updated: June 25, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)