A Study to Evaluate Albumin and Immunoglobulin in Alzheimer's Disease (AMBAR)

• Cognitive, functional and neuropsychiatric scores and overall development as measured by MMSE, NPS battery, ADCS-ADL, NPICDR-Sb, ADCS-CGIC, CSDD, C-SSRS. [ Time Frame: 14 months ] [ Designated as safety issue: No ]
• Levels of AB1-40 and AB1-42 in CSF [ Time Frame: 14 months ] [ Designated as safety issue: No ]
• Levels of AB1-40 and AB1-42 in plasma [ Time Frame: 14 months ] [ Designated as safety issue: No ]
• Changes in volumetric MRI parameters [ Time Frame: 14 months ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the changes in the cognitive, functional, behavioral and global domains based on the different applicable psychometric batteries and scales.

A clinical trial comprised of 350 subjects with probable mild to moderate Alzheimer's Disease (AD) will be conducted primarily to determine whether plasmapheresis with infusion of human albumin combined with Intravenous immunoglobulin (IVIG) is able to modify patient's cognitive, functional, behavioral and global domains. There will be 3 treatment groups and one control group. The subjects will be randomized in a 1:1:1:1 proportion.

• Biological: Albumin
  Human albumin 20%
  Other Names:

  • Albutein 20%
  • Human Albumin Grifols 20%
• Biological: Immune globulin
  Intravenous (human) immune globulin 5%
  Other Names:

  • Flebogamma DIF 5%
  • flebogammadif 5%

• Experimental: Treatment group 1
  Plasmapheresis with infusion of 20% albumin and IGIV (high dose)
  Interventions:

  • Biological: Albumin
  • Biological: Immune globulin
• Experimental: Treatment group 2
  Plasmapheresis with infusion of 20% albumin and IGIV (intermediate dose)
  Interventions:

  • Biological: Albumin
  • Biological: Immune globulin
• Experimental: Treatment group 3
  Plasmapheresis with infusion of 20% albumin
  Interventions:

  • Biological: Albumin
  • Biological: Immune globulin
• No Intervention: Control group
  Standard treatment with previously prescribed medications

Main Inclusion Criteria:

1. Males or females between 55-85 years of age at the time of signing of the informed consent document.
2. A diagnosis of Alzheimer's disease (NINCDS-ADRDA criterion), and MMSE score between >/=18 and </=26.
3. Current stable treatment with AChEIs for the previous three months.
4. The patient and a close relative or the legal representative must read the patient information sheet, agree to participation in the trial, and then sign the informed consent document (the patient personally and the close relative/legal representative).
5. The patient must be able to follow the study protocol, receive the treatment in the established time period, and continue during the follow-up interval.
6. A brain CAT or MRI study obtained in the 12 months prior to screening, showing the absence of cerebrovascular disease, must be available .
7. A stable care taker must be available, and must attend the patient study visits.

Main Exclusion Criteria:

1. Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such as for example:
2. Hemoglobin < 10 mg/dL
3. Difficult venous access precluding plasma exchange.
4. A history of frequent adverse reactions (serious or otherwise) to blood products.
5. Hypersensitivity to albumin or allergies to any of the components of Albutein® 5%.
6. History of immunoglobulin A (IgA) deficiency.
7. Known allergies to Flebogamma® DIF components such as sorbitol.
8. History of thromboembolic complications of intravenous immunoglobulins.
9. Plasma creatinine > 2 mg/dl.
10. Uncontrolled high blood pressure.
11. Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dL.
12. Heart diseases, including antecedents of coronary disease and heart failure.
13. Participation in other clinical trials, or the receipt of any other investigational drug in the three months prior to the start of the study.
14. Any condition complicating adherence to the study protocol (illness with less than one year of expected survival, toxic habits, etc.).
15. Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange.