Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Intravenous Immunoglobulin; Placebo
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Immunotherapy; Amyloid beta protein; Antibodies; Alzheimer's; Dementia

Summary:

      The overall goal of this double-blind Phase II study is to evaluate the safety, efficacy and
      biological mechanisms of action of Intravenous Immunoglobulin (IVIg) in the treatment of mild
      to moderate stage Alzheimer's disease (AD). IVIg contains antibodies against the amyloid beta
      protein that is the central component of the AD senile plaque. It is hypothesized that IVIg
      treatment will reduce the levels of beta amyloid in the brain and improve cognitive abilities
      relative to placebo. A total of 24 patients with mild to moderate AD capable of giving
      informed consent will be randomly assigned to receive either IVIg (16 patients)or saline
      placebo (8 patients) for six months. This study includes comparison of four dosing regimens
      of IVIg. Cognitive, behavioral and functional measures will be collected at baseline, three
      months and six months of treatment. Plasma samples will be collected before and after
      infusions. Subjects will undergo a lumbar puncture before and after the six months of
      treatment for cerebrospinal fluid (CSF) biomarker analyses. In addition, Positron Emission
      Tomography (PET) imaging substudies will be performed at two time points during the study.
      Following the initial 6 month placebo-controlled period, all participants have the
      opportunity to receive IVIg for an additional 12 month period in an extension study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of probable Alzheimer's disease (AD) of mild to moderate severity (as
             determined by a Mini Mental State Examination (MMSE) score of 14 - 26 inclusive).

          2. Ability to give informed consent, designate a decision-maker or have an already
             recognized decision-maker (such as a legal guardian or health care proxy).

          3. Ability to comply with testing and infusion regimen.

          4. An able caregiver willing to participate (such as a spouse, child, other relative,
             close friend, aide or other professional caregiver closely involved in helping the
             patient take care of himself/herself).

          5. Venous access suitable for repeated infusion and phlebotomy.

          6. On stable doses of approved AD medications for at least 3 months.

          7. As applicable, on stable doses of psychoactive medications (e.g. antidepressants,
             antipsychotics) for at least 6 weeks.

          8. Neuroimaging performed after symptom onset consistent with the patient's diagnosis.

          9. Clinical laboratory values within normal limits or if abnormal, judged clinically
             insignificant by the Principal Investigator.

         10. Women who want to take part in this study must either be post-menopausal, surgically
             sterilized or agree to avoid becoming pregnant during the entire period of their
             participation in this study.

        Exclusion Criteria:

          1. Non-Alzheimer dementia.

          2. Active renal disease.

          3. Abnormally high serum viscosity levels.

          4. Immunoglobulin A (IgA) deficiency.

          5. Untreated congestive heart failure, unstable angina or a history of recent myocardial
             infarction.

          6. Unstable arrhythmia.

          7. Untreated or poorly controlled hypercholesterolemia.

          8. Untreated or poorly controlled hypertension.

          9. Poorly controlled diabetes.

         10. Thrombosis (central or peripheral) in the past year.

         11. Modified Hachinski score > 5.

         12. Active cancer diagnosis, except basal cell carcinoma.

         13. Active autoimmune or neuroimmunologic disorder.

         14. History of IVIg treatment in past 6 months.

         15. Untreated major depression or other major psychiatric disorders.

         16. Known coagulopathy or platelet counts < 100,000.

         17. Positive serology for Hepatitis B or C, or HIV.

         18. Active migraines or frequent headaches (3 or more times per week).

         19. Taking immunosuppressive drugs.

         20. Chronic (more than thrice weekly) use of non-steroidal anti-inflammatory drugs
             (NSAIDs), excluding aspirin 81 milligrams daily.

         21. Received an investigational treatment for AD within 3 months of study entry.

         22. A history of or current disorder or disease that in a physician co-investigator's
             judgment may impede the subject's participation in the study, pose immoderate risk to
             the patient or confound the results of the study