Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
Condition: Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: Octagam 10%
Intervention description: FDA approved human normal immunoglobulin solution ready for intravenous administration
Intervention MeSH terms: gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a single center, open label, proof of concept, out-patient study.
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 50 Years
Maximum age: 84 Years
Healthy volunteers: No
Keywords: MCI, Alzheimer Disease, AD

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 50 to <85 years.

          2. Evidence of amyloid pathology on Florbetapir PET at screening.

          3. Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A)

          4. MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy
             and/or bilateral parietal atrophy.

          5. CDR score of 0.5

          6. Mini-Mental State Examination (MMSE) score of 24-30, inclusive.

          7. Rosen Modified Hachinski Ischemic score ≤4.

          8. 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.

          9. Agree to refrain from participating in any treatment or clinical trial targeting
             amyloid for the duration of the study.

         10. Agree to refrain from taking any herbal supplement considered to enhance cognition
             unless approved by the investigator for the duration of the study.

         11. Ability to attend all clinical visits and have an informant capable of accompanying
             the subject on specific clinic visits.

         12. 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).

         13. Fluency in English and evidence of adequate premorbid intellectual functioning.

         14. Adequate manual dexterity, visual, and auditory abilities to perform all aspects of
             the cognitive and functional assessments.

         15. Venous access suitable for repeated infusions and phlebotomy.

         16. In the opinion of the investigator, the subject and informant will be compliant and
             have a high probability of completing the study, including all scheduled evaluations
             and required tests.

        Exclusion Criteria:

          1. Has significant neurological disease other than MCI that in the opinion of the
             investigator 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. 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).

          5. Brain MRI shows moderate or severe cortical or hippocampal atrophy.

          6. Sensitivity to Florbetapir.

          7. 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.

          8. Ophthalmologic condition that would interfere with retinal amyloid imaging.

          9. 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.

         10. 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.

         11. History of cancer within the last 5 years, with the exception of nonmetastatic basal
             cell carcinoma, and squamous cell carcinoma of the skin.

         12. Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting).

         13. History or evidence of any clinically significant autoimmune disease or disorder of
             the immune system (e.g., Crohn's Disease, Rheumatoid Arthritis)

         14. Clinically significant infection within the last 30 days (e.g., chronic persistent or
             acute infection (eg, upper respiratory infection [URI], urinary tract infection
             [UTI]).

         15. Female subjects of childbearing potential.

         16. Other clinically significant abnormality on physical, neurological, laboratory, vital
             signs or ECG examination (e.g., atrial fibrillation) that could compromise the study
             or be detrimental to the subject.

         17. Weight greater than 120 kg (264 lbs).

         18. Excessive smoking defined as more than 20 cigarettes per day.

         19. History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within
             the last 2 years.

         20. Severe liver or kidney disease verified by the PI review of ALT, AST and creatinine.

         21. Known coagulopathy, thrombosis, or low platelet count.

         22. Hemoglobin less than 11 g/dL.

         23. Known deficiency to IgA.

         24. Positive serology for Hepatitis B or C, or HIV.

         25. History of anti-amyloid treatment, immunotherapy, or other experimental treatment for
             MCI or Alzheimer disease.

         26. Concurrent use of anticholinergic drugs including diphenhydramine.

         27. Current use of anticoagulant medications (except the use of aspirin 325 mg/day or
             less, plavix, aggrenox, and persantine but not for stroke).

         28. Concurrent use of opioid pain relievers and related synthetic derivatives.