Back to resultsEfficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Albutein 5%
Control
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring 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
Eligibility Criteria
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.
Sites / Locations
- Howard University
- Mid-Atlantic Geriatric/ARC
- Fundació ACE
- Hospital General Universitario Gregorio Marañon
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Albutein 5%
Control
Arm Description
Patients allocated to this arm underwent plasma exchange with Albutein 5%.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
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).
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).
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)
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)
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.
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.
Full Information
NCT ID
NCT00742417
First Posted
August 25, 2008
Last Updated
May 5, 2016
Sponsor
Instituto Grifols, S.A.
Collaborators
Grifols Biologicals, LLC
1. Study Identification
Unique Protocol Identification Number
NCT00742417
Brief Title
Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid
Official Title
Phase II Study to Evaluate the Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid, and Its Effects in Patients With Mild-moderate Alzheimer's Disease.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto Grifols, S.A.
Collaborators
Grifols Biologicals, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Albutein 5%
Arm Type
Experimental
Arm Description
Patients allocated to this arm underwent plasma exchange with Albutein 5%.
Arm Title
Control
Arm Type
Sham Comparator
Intervention Type
Biological
Intervention Name(s)
Albutein 5%
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Control
Intervention Description
Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements)
Primary Outcome Measure Information:
Title
Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels.
Description
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
Secondary Outcome Measure Information:
Title
P-Tau and Tau CSF Levels Throughout the Study.
Description
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
Title
Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company).
Description
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.
Title
Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company).
Description
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
Title
Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest).
Description
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.
Title
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD)
Description
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
Title
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC).
Description
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
Title
Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline.
Description
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
Title
Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merce Boada, MD
Organizational Affiliation
Fundació ACE
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Laura Núñez
Organizational Affiliation
Grifols Biologicals, LLC
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Antonio Paez
Organizational Affiliation
Grifols Biologicals, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Howard University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
Mid-Atlantic Geriatric/ARC
City
Manchester Township
State/Province
New Jersey
ZIP/Postal Code
08759
Country
United States
Facility Name
Fundació ACE
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08028
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid
We'll reach out to this number within 24 hrs