Alzheimer's DiseasePhase 2NCT00742417
Efficacy and Safety of Plasma Exchange With 5% Albumin in Beta-amyloid Peptide Clearance in Cerebral Spinal Fluid
A Phase 2 study testing Albutein 5% in people with Alzheimer's Disease, run by Instituto Grifols, S.A. at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Albutein 5%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jul 2007to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States2 sites
Howard University
Washington D.C., District of Columbia, 20059
Mid-Atlantic Geriatric/ARC
Whiting, New Jersey, 08759
Spain2 sites
Fundació ACE
Barcelona, Catalonia, 08028
Hospital General Universitario Gregorio Marañon
Madrid, Madrid, 28007
About this study
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.
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.
Read the 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.
- Conditions
- Alzheimer's Disease
- Being tested
- Albutein 5%, Control
- 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
- Medical subject headings
- Alzheimer Disease, Dementia, Plaque, Amyloid, Central Nervous System Diseases, Brain Diseases, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Albutein 5%Biological
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
ControlOther
Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements)
| Study group | Role | What they receive |
|---|---|---|
| Albutein 5% | Experimental | Patients allocated to this arm underwent plasma exchange with Albutein 5%. Receives: Biological: Albutein 5% |
| Control | Sham comparator | Not described Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and up to week 44
Secondary outcomes (8)
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).
Measured: Baseline, week 02, week 08, week 20, week 33 and 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).
Measured: 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.
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).
Measured: 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
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).
Measured: 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.
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)
Measured: Change from baseline at week 44
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)
Measured: Change from baseline at week 44
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.
Measured: Week 00 (baseline), week 20 and week 44
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.
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2008 (estimated)
- Study startJul 2007
- Primary completionFeb 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Grifols, S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Grifols Biologicals, LLC
- Responsible party
- Sponsor
- Investigators
- Merce Boada, MD, Principal investigator, Fundació ACELaura Núñez, Study director, Grifols Biologicals, LLCAntonio Paez, Study chair, Grifols Biologicals, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00742417
- Sponsor's protocol ID
- IG0602
- Status last verified
- May 2016
- First submitted
- 25 Aug 2008
- Last updated
- 14 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00742417
- Acronym / sponsor ID
- IG0602
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's, Dementia, Senile, Loss of cognitive abilities, Old age, Elderly, Aging, Albumin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Instituto Grifols, S.A.Industry (pharma, biotech, devices)
- Collaborators
- Grifols Biologicals, LLC
- Study start
- Jul 2007
- Primary completion
- Feb 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 27 Aug 2008 (estimated)
- Results
- Posted 14 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albutein 5% | Experimental | Biological: Albutein 5%Patients allocated to this arm underwent plasma exchange with Albutein 5%. |
| Control | Sham comparator | Other: Control |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Biological | Albutein 5% |
| ControlControl group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) | Other | Control |
Primary outcome
Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels.
Time frame: 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.
8 secondary outcomes
P-Tau and Tau CSF Levels Throughout the Study.
Time frame: Baseline, week 02, week 08, week 20, week 33 and week 44
Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company).
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.
Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company).
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
Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest).
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.
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD)
Time frame: Change from baseline at week 44
Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC).
Time frame: Change from baseline at week 44
Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline.
Time frame: Week 00 (baseline), week 20 and week 44
Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT)
Time frame: End of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Merce Boada, MD principal investigator
Fundació ACE
Laura Núñez study director
Grifols Biologicals, LLC
Antonio Paez study chair
Grifols Biologicals, LLC
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Albutein 5% in people with Alzheimer's Disease, run by Instituto Grifols, S.A. at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. (time frame: Baseline and up to week 44). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2016.