Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment
Condition: Mild Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Intervention: NewGam 10% IVIG; Placebo
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 52.0
Sex: All
Minimum age: 50 Years
Maximum age: 84 Years
Healthy volunteers: No
Keywords: Intravenous immunotherapy; Conversion to Alzheimer Disease

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.
    

Eligibility 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.