Alzheimer's Disease
Conditions
Keywords
Alzheimer's, Dementia, Senile, Loss of cognitive abilities, Old age, Elderly, Aging, Albumin, Caregiver, amyloid, beta amyloid, Central Nervous System Diseases, Brain Disease, Mental Disorders, Plasma Exchange
Brief summary
The purpose of this study was to evaluate the efficacy and safety of plasma exchange with 5% albumin in beta-amyloid peptide clearance in cerebrospinal fluid, and its effects in patients with mild-moderate Alzheimer's disease.
Detailed description
A phase II study was conducted primarily to determine whether plasma exchange with 5% human albumin is able to modify the concentration of beta-amyloid peptide in cerebrospinal fluid (CSF) in patients with AD. * There was two weeks for screening and randomization of both groups (treatment and control). * The subjects were randomized in a 1:1 proportion. After screening and randomization, treatment proceeded as follows: * three weeks of intensive treatment with two plasma exchanges per week * followed by a month and a half of maintenance treatment with one weekly plasma exchange, and * finally, three months of treatment with one plasma exchange every two weeks. The control group followed the same program, except for the plasma exchanges. After the treatment period ended, subjects followed-up for a 6-month period of time. The trial comprises a global multicenter (Spain and US), blind, randomized, controlled design. The trials key coordination is based in Spain where Dr. Boada (see Study Officials/Investigators) is the main study official.
Interventions
BIOLOGICALAlbutein 5%
18 Plasma Exchanges using Albutein 5%: * three weeks of intensive treatment with two plasma exchanges per week * six weeks of maintenance treatment with one weekly plasma exchange * three months of maintenance treatment with one plasma exchange every two weeks
OTHERControl
Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements)
Sponsors
Instituto Grifols, S.A.
Grifols Biologicals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of AD ( National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association \[NINCDS-ADRDA\] criterion), and Mini-mental Status Examination (MMSE) score between ≥18 and ≤26. * Current stable treatment with acetylcholine esterase inhibitors (AChEIs) for the previous three months. * A stable care taker must be available, and must attend the patient study visits. * The patient and a close relative or 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). * 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. * A brain Computed Axial Tomography (CAT) or Magnetic Resonance Imaging (MRI) study, obtained in the 12 months prior to recruitment, showing the absence of cerebrovascular disease, must be available.
Exclusion criteria
* Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters * A history of frequent adverse reactions (serious or otherwise) to blood products. * Hypersensitivity to albumin or allergies to any of the components of Albutein 5% Human Albumin. * Plasma creatinine \> 2 mg/dL. * Uncontrolled high blood pressure. * Liver cirrhosis or any liver problem with alanine aminotransferase (GPT) \> 2.5 x upper limit of normal (ULN), or bilirubin \> 2 mg/dL. * Heart diseases, including antecedents of coronary disease and heart failure. * Difficult venous access precluding plasma exchange. * Participation in other clinical trials, or the reception of any other investigational drug in the three months prior to the start of the study. * Any condition complicating adherence to the study protocol (illness with less than one year of expected survival, toxic habits, etc.). * Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange. * Fewer than six years of education. * Prior behavioral disorders requiring pharmacological treatment, including insomnia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Baseline and up to week 44 | Change in levels of Aβ1-42 in CSF in the period between baseline lumbar puncture (before the start of treatment) and lumbar puncture immediately after the end of the last plasma exchange (whenever this may be). Separate assays of Aβ1-42 were performed with Innotest and The Genetics Company commercial kits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. | Plasma levels of Aβ1-40 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). |
| Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44 | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). |
| Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using Innotest commercial kits). |
| P-Tau and Tau CSF Levels Throughout the Study. | Baseline, week 02, week 08, week 20, week 33 and week 44 | Levels of Tau and P-tau in CSF throughout the treatment phase and the follow-up phase (week 44). |
| Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | Change from baseline at week 44 | Change in the cognitive, functional and neuropsychiatric scores and overall development. * ADCS-ADL: Alzheimer's Disease Cooperative Study/Activities Of Daily Living (23 questions describing daily activity of the subject and requests the informer to describe the actions or behaviors observed. Increased autonomy associated to higher scores, maximum of 78 points and minimum of 0) * NPI: Neuropsychiatric Inventory Questions (12 symptom domains scored by frequency \[range=0 to 4, higher values being more frequent\] and severity \[range=1 to 3, higher values being more severe\], total score is sum of frequency x severity of all domains) * CDR-Sb: Clinical Dementia Rating (range=0 to 3, higher values being more severe) * ADCS-CGIC: Alzheimer's Disease Cooperative Study/Clinical Global Impression of Change (7-point Likert scale, 0=not assessed, 1=marked improvement, 2=moderate improvement, 3=minimal improvement, 4=no change, 5=minimal worsening, 6=moderate worsening and 7=marked worsening) |
| Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Week 00 (baseline), week 20 and week 44 | Structural changes in volume of the hippocampus, posterior cingular area, and other associated areas by Magnetic Resonance Imaging (MRI). Three measurements were made (week -2 or -1, 20 and 44). It was measured the variations versus the baseline. |
| Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | End of study | Percentage of patients with improved perfusion at the end of the study compared to their initial perfusion. Frontal, parietal and temporal lobes were evaluated from the quantified NeuroGam images. This rendered parametric images showed brain alterations with more than 2 standard deviations with respect to a normal data base. Initial parametric images were compared to the final ones and it was considered perfusion improvement those patients that showed less stretch and/or defect intensity. |
| Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | Change from baseline at week 44 | Change in the cognitive, functional and neuropsychiatric scores and overall development. * MMSE: Mini Mental State Examination Score (range = 0 to 30, with lower values indicating impairment) * ADAS-Cog: Alzheimer's Disease Assessment Scale, Cognitive Subscale (range = 0 to 70, with higher values indicating impairment) * NPS (Neuropsychological battery): •SDMT (Symbol Digit Modalities Test, range = 0 to 110, with lower values indicating impairment), •SVF (Semantic Verbal Fluency Test, with a maximum of 44 words in 60 seconds), •PVF F, A and S (Phonetic Verbal Fluency Test, with a maximum of 44 words in 60 seconds), •BNT (Boston Naming Test, with a maximum of 15 pictures), •RAVLT (Rey Auditory Verbal Learning Test, with 15 words the patient should listen and remind) * CSDD (Cornell Scale for Depression in Dementia, 0 = none; 1 =mild or intermittent; 2 = severe) |
Countries
Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Albutein 5% 18 Plasma Exchanges using Albutein 5%:
* three weeks of intensive treatment with two plasma exchanges per week
* six weeks of maintenance treatment with one weekly plasma exchange
* three months of maintenance treatment with one plasma exchange every two weeks | 19 |
| Control Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) | 20 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intensive Period | Adverse Event | 2 | 0 |
| Intensive Period | Withdrawal by Subject | 1 | 1 |
| Randomized | Physician Decision | 1 | 0 |
| Randomized | Withdrawal by legal representative | 0 | 1 |
| Randomized | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Control | Total | Albutein 5% |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 22 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 17 Participants | 7 Participants |
| Height | 159.3 cm STANDARD_DEVIATION 9.4 | 158.3 cm STANDARD_DEVIATION 10.1 | 156.8 cm STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 15 Participants | 30 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
| Weight | 66.0 Kg STANDARD_DEVIATION 16.6 | 65.1 Kg STANDARD_DEVIATION 15.5 | 64.0 Kg STANDARD_DEVIATION 14.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 19 | 14 / 20 |
| serious Total, serious adverse events | 3 / 19 | 2 / 20 |
Outcome results
Primary
Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels.
Change in levels of Aβ1-42 in CSF in the period between baseline lumbar puncture (before the start of treatment) and lumbar puncture immediately after the end of the last plasma exchange (whenever this may be). Separate assays of Aβ1-42 were performed with Innotest and The Genetics Company commercial kits.
Time frame: Baseline and up to week 44
Population: The efficacy analyses were performed with the full analysis set (FAS) population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions (or sham procedures) during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Albutein 5% | Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Aβ1-42 Innotest | 75.3 pg/mL |
| Albutein 5% | Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Aβ1-42 The Genetics Company | -86.2 pg/mL |
| Control (Sham Procedure) | Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Aβ1-42 Innotest | -45.5 pg/mL |
| Control (Sham Procedure) | Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Aβ1-42 The Genetics Company | -283.0 pg/mL |
Secondary
Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company).
Plasma levels of Aβ1-40 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits).
Time frame: Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44.
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE1 (Intensive) (n=18; n=19) | 120.3 pg/mL | Standard Deviation 57.1 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE13 (Maintenance II) (n=15; n=19) | 150.0 pg/mL | Standard Deviation 66 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE7(Maintenance I) (n=14; n=17) | 150.7 pg/mL | Standard Deviation 51.3 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE18 (Maintenance II) (n=14; n=18) | 245.9 pg/mL | Standard Deviation 102 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE6 (Intensive) (n=15; n=19) | 255.7 pg/mL | Standard Deviation 98.4 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (33 week) (n=14; n=15) | 153.3 pg/mL | Standard Deviation 50.6 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE12 (Maintenance I) (n=14; n=18) | 287.1 pg/mL | Standard Deviation 98.6 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (44 week) (n=15; n=14) | 146.7 pg/mL | Standard Deviation 41.7 |
| Albutein 5% | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 Baseline (Albutein n=18; Control n=18) | 121.3 pg/mL | Standard Deviation 52.6 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (44 week) (n=15; n=14) | 147.1 pg/mL | Standard Deviation 23.4 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 Baseline (Albutein n=18; Control n=18) | 126.7 pg/mL | Standard Deviation 43.2 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE1 (Intensive) (n=18; n=19) | 105.8 pg/mL | Standard Deviation 47.7 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE6 (Intensive) (n=15; n=19) | 123.9 pg/mL | Standard Deviation 53.7 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE7(Maintenance I) (n=14; n=17) | 139.7 pg/mL | Standard Deviation 41.8 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE12 (Maintenance I) (n=14; n=18) | 150.4 pg/mL | Standard Deviation 54.4 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 PRE-PE13 (Maintenance II) (n=15; n=19) | 129.6 pg/mL | Standard Deviation 40.3 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-40 POST-PE18 (Maintenance II) (n=14; n=18) | 135.4 pg/mL | Standard Deviation 50.2 |
| Control (Sham Procedure) | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (33 week) (n=14; n=15) | 136.9 pg/mL | Standard Deviation 37.3 |
Secondary
Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest).
Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using Innotest commercial kits).
Time frame: Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44.
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Follow up (33 week) (n=14; n=15) | 10.1 pg/mL | Standard Deviation 12.9 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 Baseline (Albutein n=18; Control n=18) | 40.1 pg/mL | Standard Deviation 77.1 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE1 (Intensive) (n=18; n=19) | 20.4 pg/mL | Standard Deviation 21.5 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) | 29.1 pg/mL | Standard Deviation 23.2 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE7 (Maintenance I) (n=14; n=17) | 29.5 pg/mL | Standard Deviation 30.9 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) | 25.1 pg/mL | Standard Deviation 21 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) | 36.4 pg/mL | Standard Deviation 35.9 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) | 37.1 pg/mL | Standard Deviation 40.9 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Follow up (44 week) (n=15; n=14) | 11.3 pg/mL | Standard Deviation 11.4 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) | 45.3 pg/mL | Standard Deviation 42.4 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) | 41.4 pg/mL | Standard Deviation 35.5 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 Baseline (Albutein n=18; Control n=18) | 49.5 pg/mL | Standard Deviation 43.7 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Follow up (33 week) (n=14; n=15) | 10.2 pg/mL | Standard Deviation 16.7 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE1 (Intensive) (n=18; n=19) | 33.4 pg/mL | Standard Deviation 29.1 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) | 51.2 pg/mL | Standard Deviation 48.3 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) | 45.4 pg/mL | Standard Deviation 31.3 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Follow up (44 week) (n=15; n=14) | 11.7 pg/mL | Standard Deviation 20.8 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Aβ1-42 PRE-PE7 (Maintenance I) (n=14; n=17) | 58.5 pg/mL | Standard Deviation 68.1 |
Secondary
Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company).
Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits).
Time frame: Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 Baseline (Albutein n=18; Control n=18) | 2.8 pg/mL | Standard Deviation 9.3 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE1 (Intensive) (n=18; n=19) | 6.6 pg/mL | Standard Deviation 16.3 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) | 9.8 pg/mL | Standard Deviation 15.6 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE7 (Maintenance) (n=14; n=17) | 0.0 pg/mL | Standard Deviation 0 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) | 10.7 pg/mL | Standard Deviation 15.9 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) | 6.9 pg/mL | Standard Deviation 11.8 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) | 8.0 pg/mL | Standard Deviation 16.7 |
| Albutein 5% | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (44 week) (n=15; n=14) | 1.7 pg/mL | Standard Deviation 6.6 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Follow up (44 week) (n=15; n=14) | 10.2 pg/mL | Standard Deviation 18.2 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 Baseline (Albutein n=18; Control n=18) | 33.7 pg/mL | Standard Deviation 81.4 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) | 5.9 pg/mL | Standard Deviation 14.3 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE1 (Intensive) (n=18; n=19) | 20.9 pg/mL | Standard Deviation 58.4 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) | 7.1 pg/mL | Standard Deviation 14.3 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) | 4.9 pg/mL | Standard Deviation 11.8 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) | 8.2 pg/mL | Standard Deviation 17.2 |
| Control (Sham Procedure) | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Aβ1-42 PRE-PE7 (Maintenance) (n=14; n=17) | 4.5 pg/mL | Standard Deviation 12.9 |
Secondary
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC).
Change in the cognitive, functional and neuropsychiatric scores and overall development. * ADCS-ADL: Alzheimer's Disease Cooperative Study/Activities Of Daily Living (23 questions describing daily activity of the subject and requests the informer to describe the actions or behaviors observed. Increased autonomy associated to higher scores, maximum of 78 points and minimum of 0) * NPI: Neuropsychiatric Inventory Questions (12 symptom domains scored by frequency \[range=0 to 4, higher values being more frequent\] and severity \[range=1 to 3, higher values being more severe\], total score is sum of frequency x severity of all domains) * CDR-Sb: Clinical Dementia Rating (range=0 to 3, higher values being more severe) * ADCS-CGIC: Alzheimer's Disease Cooperative Study/Clinical Global Impression of Change (7-point Likert scale, 0=not assessed, 1=marked improvement, 2=moderate improvement, 3=minimal improvement, 4=no change, 5=minimal worsening, 6=moderate worsening and 7=marked worsening)
Time frame: Change from baseline at week 44
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | NPI (total score) (n=15; n=14) | -1.7 units on a scale | Standard Deviation 14.1 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | CDR Sb score (n=15; n=14) | 1.7 units on a scale | Standard Deviation 1.5 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | NPI (total distress) (n=15; n=14) | -2.1 units on a scale | Standard Deviation 7.8 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | ADCS-CGIC (n=15; n=14) | 1.5 units on a scale | Standard Deviation 0.7 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | ADCS-ADL (Albutein n=15; Control n=14) | -7.1 units on a scale | Standard Deviation 11.4 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | ADCS-CGIC (n=15; n=14) | 1.2 units on a scale | Standard Deviation 1.1 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | ADCS-ADL (Albutein n=15; Control n=14) | -4.9 units on a scale | Standard Deviation 10.9 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | NPI (total score) (n=15; n=14) | -4.0 units on a scale | Standard Deviation 13.7 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | NPI (total distress) (n=15; n=14) | -3.6 units on a scale | Standard Deviation 6.4 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | CDR Sb score (n=15; n=14) | 1.4 units on a scale | Standard Deviation 3.3 |
Secondary
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD)
Change in the cognitive, functional and neuropsychiatric scores and overall development. * MMSE: Mini Mental State Examination Score (range = 0 to 30, with lower values indicating impairment) * ADAS-Cog: Alzheimer's Disease Assessment Scale, Cognitive Subscale (range = 0 to 70, with higher values indicating impairment) * NPS (Neuropsychological battery): •SDMT (Symbol Digit Modalities Test, range = 0 to 110, with lower values indicating impairment), •SVF (Semantic Verbal Fluency Test, with a maximum of 44 words in 60 seconds), •PVF F, A and S (Phonetic Verbal Fluency Test, with a maximum of 44 words in 60 seconds), •BNT (Boston Naming Test, with a maximum of 15 pictures), •RAVLT (Rey Auditory Verbal Learning Test, with 15 words the patient should listen and remind) * CSDD (Cornell Scale for Depression in Dementia, 0 = none; 1 =mild or intermittent; 2 = severe)
Time frame: Change from baseline at week 44
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | MMSE (Albutein n=15; Control n=14) | -1.7 units on a scale | Standard Deviation 3.2 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | ADAS-Cog (n=15; n=14) | 3.9 units on a scale | Standard Deviation 6.2 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (SDMT) (n=15; n=14) | 1.3 units on a scale | Standard Deviation 11.2 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (SVF) (n=15; n=14) (n=15; n=14) | 2.5 units on a scale | Standard Deviation 3.2 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(F)) (n=15; n=14) | -0.2 units on a scale | Standard Deviation 2.6 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(A)) (n=15; n=14) | 0.2 units on a scale | Standard Deviation 3.4 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(S)) (n=15; n=14) | 1.1 units on a scale | Standard Deviation 1.8 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (BNT) (n=15; n=14) | 1.7 units on a scale | Standard Deviation 2.5 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 1) (n=15; n=14) | 1.1 units on a scale | Standard Deviation 1.9 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 2) (n=15; n=14) | 0.3 units on a scale | Standard Deviation 1.6 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 3) (n=15; n=14) | 0.1 units on a scale | Standard Deviation 2.1 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 4) (n=15; n=14) | -1.1 units on a scale | Standard Deviation 1.8 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 5) (n=15; n=14) | -0.3 units on a scale | Standard Deviation 2.1 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Delayed) (n=15; n=14) | 0.5 units on a scale | Standard Deviation 1.6 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | CSDD (patient) (n=10; n=7) | -0.8 units on a scale | Standard Deviation 2.9 |
| Albutein 5% | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | CSDD (caregiver) (n=13; n=11) | 1.0 units on a scale | Standard Deviation 4.1 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | CSDD (caregiver) (n=13; n=11) | 1.8 units on a scale | Standard Deviation 3.7 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | MMSE (Albutein n=15; Control n=14) | -3.8 units on a scale | Standard Deviation 5.9 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 1) (n=15; n=14) | -0.1 units on a scale | Standard Deviation 2 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | ADAS-Cog (n=15; n=14) | 6.6 units on a scale | Standard Deviation 10.5 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 5) (n=15; n=14) | -1.4 units on a scale | Standard Deviation 1.8 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (SDMT) (n=15; n=14) | -0.5 units on a scale | Standard Deviation 2.5 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 2) (n=15; n=14) | -1.0 units on a scale | Standard Deviation 1.5 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (SVF) (n=15; n=14) (n=15; n=14) | -0.4 units on a scale | Standard Deviation 3.8 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | CSDD (patient) (n=10; n=7) | -2.1 units on a scale | Standard Deviation 5.6 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(F)) (n=15; n=14) | 0.6 units on a scale | Standard Deviation 3.8 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 3) (n=15; n=14) | -0.3 units on a scale | Standard Deviation 2 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(A)) (n=15; n=14) | 0.2 units on a scale | Standard Deviation 3.2 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Delayed) (n=15; n=14) | 0.1 units on a scale | Standard Deviation 1 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (PVF(S)) (n=15; n=14) | -0.6 units on a scale | Standard Deviation 3.3 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (RAVLT Intermediate 4) (n=15; n=14) | -0.9 units on a scale | Standard Deviation 2.5 |
| Control (Sham Procedure) | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | NPS (BNT) (n=15; n=14) | 0.3 units on a scale | Standard Deviation 4.1 |
Secondary
Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline.
Structural changes in volume of the hippocampus, posterior cingular area, and other associated areas by Magnetic Resonance Imaging (MRI). Three measurements were made (week -2 or -1, 20 and 44). It was measured the variations versus the baseline.
Time frame: Week 00 (baseline), week 20 and week 44
Population: We analyzed two groups of patients, a treatment group of 20 patients, and a control group, also of 20 patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 00) | 1.90 cubic centimetres (cc) | Standard Deviation 0.41 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 20) | 1.76 cubic centimetres (cc) | Standard Deviation 0.45 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 44) | 1.64 cubic centimetres (cc) | Standard Deviation 0.43 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 00) | 2.04 cubic centimetres (cc) | Standard Deviation 0.41 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 20) | 1.98 cubic centimetres (cc) | Standard Deviation 0.41 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 44) | 1.88 cubic centimetres (cc) | Standard Deviation 0.35 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 00) | 10.60 cubic centimetres (cc) | Standard Deviation 1.34 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 20) | 10.22 cubic centimetres (cc) | Standard Deviation 1.58 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 44) | 10.60 cubic centimetres (cc) | Standard Deviation 1.48 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 00) | 1034.38 cubic centimetres (cc) | Standard Deviation 99.77 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 20) | 990.31 cubic centimetres (cc) | Standard Deviation 83.42 |
| Albutein 5% | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 44) | 985.43 cubic centimetres (cc) | Standard Deviation 86.1 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 20) | 1042.70 cubic centimetres (cc) | Standard Deviation 119.93 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 00) | 1.91 cubic centimetres (cc) | Standard Deviation 0.48 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 00) | 10.38 cubic centimetres (cc) | Standard Deviation 0.8 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 20) | 1.85 cubic centimetres (cc) | Standard Deviation 0.4 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 00) | 1064.38 cubic centimetres (cc) | Standard Deviation 130.29 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus L (week 44) | 1.76 cubic centimetres (cc) | Standard Deviation 0.39 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 20) | 10.39 cubic centimetres (cc) | Standard Deviation 0.8 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 00) | 2.14 cubic centimetres (cc) | Standard Deviation 0.38 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Total Intracranial Volume (week 44) | 1026.51 cubic centimetres (cc) | Standard Deviation 148.43 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 20) | 2.07 cubic centimetres (cc) | Standard Deviation 0.32 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Post Cingulate (week 44) | 10.23 cubic centimetres (cc) | Standard Deviation 1.06 |
| Control (Sham Procedure) | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Hippocampus R (week 44) | 1.96 cubic centimetres (cc) | Standard Deviation 0.34 |
Secondary
P-Tau and Tau CSF Levels Throughout the Study.
Levels of Tau and P-tau in CSF throughout the treatment phase and the follow-up phase (week 44).
Time frame: Baseline, week 02, week 08, week 20, week 33 and week 44
Population: The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (baseline) (Albutein n=18; Control n=19) | 87.7 pg/mL | Standard Deviation 51.4 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 02) (n=16; n=19) | 87.5 pg/mL | Standard Deviation 43.8 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 08) (n=15; n=18) | 78.9 pg/mL | Standard Deviation 46.3 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 20) (n=15; n=18) | 88.4 pg/mL | Standard Deviation 42 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 33) (n=14; n=15) | 91.9 pg/mL | Standard Deviation 57.6 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 44) (n=14; n=14) | 89.9 pg/mL | Standard Deviation 54.5 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (baseline) (n=18; n=19) | 571.2 pg/mL | Standard Deviation 354.4 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 02) (n=16; n=19) | 669.8 pg/mL | Standard Deviation 496.8 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 08) (n=15; n=18) | 482.2 pg/mL | Standard Deviation 307.4 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 20) (n=15; n=18) | 537.1 pg/mL | Standard Deviation 253.5 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 33) (n=14; n=15) | 539.5 pg/mL | Standard Deviation 309.6 |
| Albutein 5% | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 44) (n=14; n=14) | 544.3 pg/mL | Standard Deviation 299.4 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 33) (n=14; n=15) | 483.5 pg/mL | Standard Deviation 318.5 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (baseline) (Albutein n=18; Control n=19) | 79.0 pg/mL | Standard Deviation 35.1 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (baseline) (n=18; n=19) | 589.6 pg/mL | Standard Deviation 344.2 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 02) (n=16; n=19) | 94.1 pg/mL | Standard Deviation 46.7 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 20) (n=15; n=18) | 555.6 pg/mL | Standard Deviation 308.3 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 08) (n=15; n=18) | 78.0 pg/mL | Standard Deviation 41.3 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 02) (n=16; n=19) | 711.0 pg/mL | Standard Deviation 388.8 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 20) (n=15; n=18) | 84.1 pg/mL | Standard Deviation 36.8 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 44) (n=14; n=14) | 544.1 pg/mL | Standard Deviation 347.4 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 33) (n=14; n=15) | 78.7 pg/mL | Standard Deviation 40.4 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | Tau (week 08) (n=15; n=18) | 526.3 pg/mL | Standard Deviation 326.9 |
| Control (Sham Procedure) | P-Tau and Tau CSF Levels Throughout the Study. | P-Tau (week 44) (n=14; n=14) | 85.1 pg/mL | Standard Deviation 46.5 |
Secondary
Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT)
Percentage of patients with improved perfusion at the end of the study compared to their initial perfusion. Frontal, parietal and temporal lobes were evaluated from the quantified NeuroGam images. This rendered parametric images showed brain alterations with more than 2 standard deviations with respect to a normal data base. Initial parametric images were compared to the final ones and it was considered perfusion improvement those patients that showed less stretch and/or defect intensity.
Time frame: End of study
Population: We analyzed two groups of patients, a treatment group of 20 patients, and a control group, also of 20 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albutein 5% | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Parietal | 25 percentage of participants |
| Albutein 5% | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Temporal | 25 percentage of participants |
| Albutein 5% | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Frontal | 5 percentage of participants |
| Control (Sham Procedure) | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Parietal | 20 percentage of participants |
| Control (Sham Procedure) | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Temporal | 10 percentage of participants |
| Control (Sham Procedure) | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Frontal | 5 percentage of participants |