Details

Details

Title A multicenter, randomized, controlled study to evaluate the efficacy and safety of short-term plasma exchange followed by long-term plasmapheresis with infusion of human albumin combined with intravenous immunoglobulin in patients with mild-moderate Alzheimer’s disease.

CC 14-351

Hospital Main Campus

Disease Von Willebrand Diseaes (VWD)

Description

Description

Primary objective
  • To evaluate the changes in the cognitive, functional, behavioral and global domains based on the different applicable psychometric batteries and scales.
Secondary objectives:
  • To determine the changes in the concentration of beta-amyloid peptide in plasma and cerebrospinal fluid (CSF) in the treatment group of patients with Alzheimer's disease (AD)
  • To evaluate the structural changes in volume of the hippocampus, posterior cingulate area, and other associated areas based on neuroimaging studies with MRI (variations versus baseline).
  • To determine functional brain changes through FDG-PET (fluordeoxyglucose-PET).
  • To determine whether plasma exchange with human albumin combined with IVIG is safe, taking into account the following factors:
    • Type, severity and frequency of adverse reactions during and after the procedure and infusions.
    • Changes in vital signs and clinically relevant changes, according to the laboratory test findings.
    • Control of episodes of cerebrovascular accidents with MRI.
Inclusion Criteria

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 and/or memantine 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, should be available. Nevertheless, it is mandatory to use the MRI obtained during the screening period to rule out any cerebrovascular disease such as microhemorrages, infarction, hematoma, stroke, meningioma or other finding that could affect patient safety.
  7. A stable care taker must be available, and must attend the patient study visits.
Exclusion Criteria

Exclusion Criteria

  1. Any contraindication for plasma exchange due to behavioral disorders or abnormalcoagulation parameters, such as for example:
    • Hypocalcemia (Ca++ < 8.7 mg/dL).
    • Thrombocytopenia (<100,000/mL).
    • Fibrinogen <1.5 g/L.
    • Prothrombin time (Quick) p<60% versus control (INR>1.5).
    • Beta-blocker treatment and bradycardia <55/min.
    • Treatment with ACEIs (increased risk of allergic reactions).
  2. Hemoglobin < 10 g/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 (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher despite regular treatment during the last 3 months).
  11. Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dL.
  12. Heart diseases as evidenced by myocardial infarction, severe or unstable angina, or heart failure (New York Heart Association Class II, III or IV) in the past 12 months.
  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, known drugs or alcohol abuse, etc.).
  15. Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange.
  16. Fewer than six years of education (exclusion criteria under medical criterion).
  17. Less than three months with stable treatment for behavioral disorders including insomnia.
  18. Patients being treated with anticoagulants or antiplatelet therapy (antiaggregants) should not be recruited in the study.