Alzheimer's DiseaseNCT01403519
Innovative Biomarkers in Alzheimer's Disease and Frontotemporal Dementia (FTD): Preventative and Personalized
An observational study of Alzheimer's Disease, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
Tau pathology and tangles have been associated with cognitive dysfunction causing neurodegeneration. AD, the most abundant tauopathy is characterized by amyloid plaques and tau tangles. Read more about this study
- Who is it for?
- Ages 45 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- How many people
- 70 participants
- Where
- 1 siteIsrael
- Study dates
- Jul 2011to Jan 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
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 45 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.
Who may be able to join
- Minimal cognitive impairment (MCI) and Alzheimer's disease (AD) patients, men and women, age 45-80 will be asked to participate in the present study.
- MCI will be diagnosed when on cognitive evaluation the patients will score <1.5 SD on memory tests and will not be demented. AD will be diagnosed according to NINCDS-ADRDA research criteria. Patients will be stratified by age and cognitive (dementia) status. Disease severity for AD: mild to moderate (MMSE >16) AD.
- Frontotemporal dementia: patients with a clinical diagnosis of frontotemporal dementia [behavioral variants (bv)FTD, progressive nonfluent aphasia (PNFA), or semantic dementia] and the related syndromes corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) will be included.
- Inclusion criteria (controls): men and women, ages 45-80, willing to participate in the study and donate a blood samples.
Who cannot join
- (patients and controls):
- Subjects unable/unwilling to sign an informed consent.
- Patients with associated medical condition: alcoholism, immune diseases and end stage medical conditions.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Rambam Hospital
Haifa, 31096
Judith Aharon-Peretz, M.D., 972-4-8542637, jaharon@rambam.health.gov.il
About this study
Tau pathology and tangles have been associated with cognitive dysfunction causing neurodegeneration. AD, the most abundant tauopathy is characterized by amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases including frontal atrophy associated with cognitive clinical dysfunction of frontal dysexecutive syndrome, progressive nonfluent aphasia and semantic dementia as recently reviewed (Gozes 2010). It is the investigators aim to follow other protein expression [as per recent publications (Marksteiner et al., 2011)] in blood and CSF samples from those tauopathies.
Significance: Results should establish the possibility of using tau and other proteins as markers for early detection and disease progression in FTD, also in comparison to Alzheimer's disease (AD).
Read the detailed description
Assessing biomarkers in Alzheimer's disease and frontotemporal dementia
- Specific Aims To enhance the field of biomarker recognition and facilitate preventative and personalized medicine we are now posing the following question, does the Israeli patient population present similar plasma protein profile as described before for other populations (Marksteiner et al., 2011). Studies will be carried out by RNA transcript quantification, quantitative real time polymerase chain reaction (blood cells and CSF) and immunochemical detection at the protein level (CSF and serum).
- Methods:
Lymphocytes:
Human lymphocytes are isolated from 10 ml of venous blood using the Ficoll Paque method (de Rock and Taylor 1977; McCauley and Hartmann, 1982), for RNA extraction and determinations we shall follow-up the methods described in our manuscripts (Dresner et al., 2011).
Blood plasma and serum will be prepared as outlined in www.peoimmune.com. Protein quantitation will be carried out using the Tri reagent (Sigma) which allows for simultaneous preparation of RNA, DNA and protein and plasma immunodepletion and albumin depletion kits from Sigma.
Protein quantification: this will be carried out on cellular proteins and also on plasma proteins by SDS-polyacrylamide gel electrophoresis, followed by western analysis.
CSF samples will be collected through a spinal needle inserted into the L4-L5 or L3-L4 vertebral space with the subject in the lateral decubitus position. One ml of CSF derived from each patient will be immediately immersed in ice, with subsequent maintenance at -70 degrees C (or in dry ice during shipping) until the time of the assay. Half ml of each CSF sample will be concentrated by lyophilization in a Speed-Vac (Holten, Gydevang, Denmark) to about 0.1ml. CSF protein immunoblotting will be performed using a similar methodology as described above [and see also(Kozlovsky et al., 2004)]. Protein expression will be analyzed by western blots (Shiryaev et al., 2010).
Number of patients:
We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.
Professor Aharon-Peretz will evaluate patients with suspected Alzheimer's disease and frontotemporal dementia and include patients at various disease stages in a stratified manner (mild, moderate and severe). All patients will have signed an informed consent form, as per Helsinki guidelines. Clinical evaluation will include: physical and neurological evaluation. All patients will be asked to donate 50 ml blood and selected patients will undergo lumber puncture. The lumber puncture will be performed with the neurological work up. Professor Gozes will coordinate the scientific aspect of the study.
Study coordinators:
Scientific: Professor Illana Gozes, PhD, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Director, The Adams Super Center for Brain Studies, Tel Aviv University: igozes@post.tau.ac.il Clinical material: Professor Judith Aharon-Peretz, MD, Head of "Cognitive Neurology Unit" Rambam Rambam-Health Care Campus, Haifa, Israel
- Conditions
- Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's disease patients | Patients blood and CSF samples | |
| Control group | Blood and CSF samples | |
| FTD patients | Blood ad CSF samples |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2014 (estimated)
- Study completionJan 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Investigators
- Judith Aharon-Peretz, M.D., Principal investigator, Rambam Health Care CampusIllana Gozes, Ph.D., Principal investigator, Tel Aviv University, Sackler School of Medicine, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403519
- Sponsor's protocol ID
- 437-10CTIL
- Status last verified
- Jul 2011
- First submitted
- 6 Jul 2011
- Last updated
- 27 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Gozes I. Tau pathology and future therapeutics. Curr Alzheimer Res. 2010 Dec;7(8):685-96. doi: 10.2174/156720510793611628.
PubMed 20678069Marksteiner J, Kemmler G, Weiss EM, Knaus G, Ullrich C, Mechtcheriakov S, Oberbauer H, Auffinger S, Hinterholzl J, Hinterhuber H, Humpel C. Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2011 Mar;32(3):539-40. doi: 10.1016/j.neurobiolaging.2009.03.011. Epub 2009 Apr 22.
PubMed 19395124de Rock E, Taylor N. An easy method of layering blood over Ficoll-Paque gradients. J Immunol Methods. 1977;17(3-4):373-4. doi: 10.1016/0022-1759(77)90120-x. No abstract available.
PubMed 562380McCauley I, Hartmann PE. The estimation of B lymphocytes and their subpopulations in pigs. A comparison between a method using whole blood and one using Ficoll-Paque purified mononuclear cells. J Immunol Methods. 1982;50(1):33-8. doi: 10.1016/0022-1759(82)90301-5.
PubMed 6979582Dresner E, Agam G, Gozes I. Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia. Eur Neuropsychopharmacol. 2011 May;21(5):355-61. doi: 10.1016/j.euroneuro.2010.06.004. Epub 2010 Jul 3.
PubMed 20598862Kozlovsky N, Regenold WT, Levine J, Rapoport A, Belmaker RH, Agam G. GSK-3beta in cerebrospinal fluid of schizophrenia patients. J Neural Transm (Vienna). 2004 Aug;111(8):1093-8. doi: 10.1007/s00702-003-0127-0. Epub 2004 Apr 27.
PubMed 15254796Shiryaev N, Jouroukhin Y, Gozes I. 3R tau expression modifies behavior in transgenic mice. J Neurosci Res. 2010 Sep;88(12):2727-35. doi: 10.1002/jnr.22431.
PubMed 20544828
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Innovative Biomarkers in Alzheimer's Disease and Frontotemporal Dementia (FTD): Preventative and Personalized
- ClinicalTrials.gov ID
- NCT01403519
- Acronym / sponsor ID
- 437-10CTIL
- Conditions
- Alzheimer's Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Jan 2014 (estimated)
- Study completion
- Jan 2014 (estimated)
- First posted
- 27 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tau pathology and tangles have been associated with cognitive dysfunction causing neurodegeneration. AD, the most abundant tauopathy is characterized by amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases including frontal atrophy associated with cognitive clinical dysfunction of frontal dysexecutive syndrome, progressive nonfluent aphasia and semantic dementia as recently reviewed (Gozes 2010). It is the investigators aim to follow other protein expression [as per recent publications (Marksteiner et al., 2011)] in blood and CSF samples from those tauopathies.
Significance: Results should establish the possibility of using tau and other proteins as markers for early detection and disease progression in FTD, also in comparison to Alzheimer's disease (AD).
Detailed description
Assessing biomarkers in Alzheimer's disease and frontotemporal dementia
- Specific Aims To enhance the field of biomarker recognition and facilitate preventative and personalized medicine we are now posing the following question, does the Israeli patient population present similar plasma protein profile as described before for other populations (Marksteiner et al., 2011). Studies will be carried out by RNA transcript quantification, quantitative real time polymerase chain reaction (blood cells and CSF) and immunochemical detection at the protein level (CSF and serum).
- Methods:
Lymphocytes:
Human lymphocytes are isolated from 10 ml of venous blood using the Ficoll Paque method (de Rock and Taylor 1977; McCauley and Hartmann, 1982), for RNA extraction and determinations we shall follow-up the methods described in our manuscripts (Dresner et al., 2011).
Blood plasma and serum will be prepared as outlined in www.peoimmune.com. Protein quantitation will be carried out using the Tri reagent (Sigma) which allows for simultaneous preparation of RNA, DNA and protein and plasma immunodepletion and albumin depletion kits from Sigma.
Protein quantification: this will be carried out on cellular proteins and also on plasma proteins by SDS-polyacrylamide gel electrophoresis, followed by western analysis.
CSF samples will be collected through a spinal needle inserted into the L4-L5 or L3-L4 vertebral space with the subject in the lateral decubitus position. One ml of CSF derived from each patient will be immediately immersed in ice, with subsequent maintenance at -70 degrees C (or in dry ice during shipping) until the time of the assay. Half ml of each CSF sample will be concentrated by lyophilization in a Speed-Vac (Holten, Gydevang, Denmark) to about 0.1ml. CSF protein immunoblotting will be performed using a similar methodology as described above [and see also(Kozlovsky et al., 2004)]. Protein expression will be analyzed by western blots (Shiryaev et al., 2010).
Number of patients:
We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.
Professor Aharon-Peretz will evaluate patients with suspected Alzheimer's disease and frontotemporal dementia and include patients at various disease stages in a stratified manner (mild, moderate and severe). All patients will have signed an informed consent form, as per Helsinki guidelines. Clinical evaluation will include: physical and neurological evaluation. All patients will be asked to donate 50 ml blood and selected patients will undergo lumber puncture. The lumber puncture will be performed with the neurological work up. Professor Gozes will coordinate the scientific aspect of the study.
Study coordinators:
Scientific: Professor Illana Gozes, PhD, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Director, The Adams Super Center for Brain Studies, Tel Aviv University: igozes@post.tau.ac.il Clinical material: Professor Judith Aharon-Peretz, MD, Head of "Cognitive Neurology Unit" Rambam Rambam-Health Care Campus, Haifa, Israel
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's disease patients | – | –Patients blood and CSF samples |
| Control group | – | –Blood and CSF samples |
| FTD patients | – | –Blood ad CSF samples |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.
Key inclusion criteria (4 listed)
- Minimal cognitive impairment (MCI) and Alzheimer's disease (AD) patients, men and women, age 45-80 will be asked to participate in the present study.
- MCI will be diagnosed when on cognitive evaluation the patients will score <1.5 SD on memory tests and will not be demented. AD will be diagnosed according to NINCDS-ADRDA research criteria. Patients will be stratified by age and cognitive (dementia) status. Disease severity for AD: mild to moderate (MMSE >16) AD.
- Frontotemporal dementia: patients with a clinical diagnosis of frontotemporal dementia [behavioral variants (bv)FTD, progressive nonfluent aphasia (PNFA), or semantic dementia] and the related syndromes corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) will be included.
- Inclusion criteria (controls): men and women, ages 45-80, willing to participate in the study and donate a blood samples.
Key exclusion criteria (3 listed)
- (patients and controls):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2011.
- Background: PubMed 20678069Gozes I. Tau pathology and future therapeutics. Curr Alzheimer Res. 2010 Dec;7(8):685-96. doi: 10.2174/156720510793611628.
- Background: PubMed 19395124Marksteiner J, Kemmler G, Weiss EM, Knaus G, Ullrich C, Mechtcheriakov S, Oberbauer H, Auffinger S, Hinterholzl J, Hinterhuber H, Humpel C. Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2011 Mar;32(3):539-40. doi: 10.1016/j.neurobiolaging.2009.03.011. Epub 2009 Apr 22.
- Background: PubMed 562380de Rock E, Taylor N. An easy method of layering blood over Ficoll-Paque gradients. J Immunol Methods. 1977;17(3-4):373-4. doi: 10.1016/0022-1759(77)90120-x. No abstract available.
- Background: PubMed 6979582McCauley I, Hartmann PE. The estimation of B lymphocytes and their subpopulations in pigs. A comparison between a method using whole blood and one using Ficoll-Paque purified mononuclear cells. J Immunol Methods. 1982;50(1):33-8. doi: 10.1016/0022-1759(82)90301-5.
- Background: PubMed 20598862Dresner E, Agam G, Gozes I. Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia. Eur Neuropsychopharmacol. 2011 May;21(5):355-61. doi: 10.1016/j.euroneuro.2010.06.004. Epub 2010 Jul 3.
- Background: PubMed 15254796Kozlovsky N, Regenold WT, Levine J, Rapoport A, Belmaker RH, Agam G. GSK-3beta in cerebrospinal fluid of schizophrenia patients. J Neural Transm (Vienna). 2004 Aug;111(8):1093-8. doi: 10.1007/s00702-003-0127-0. Epub 2004 Apr 27.
- Background: PubMed 20544828Shiryaev N, Jouroukhin Y, Gozes I. 3R tau expression modifies behavior in transgenic mice. J Neurosci Res. 2010 Sep;88(12):2727-35. doi: 10.1002/jnr.22431.
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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.
Judith Aharon-Peretz, M.D. principal investigator
Rambam Health Care Campus
Illana Gozes, Ph.D. principal investigator
Tel Aviv University, Sackler School of Medicine, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer's Disease, run by Rambam Health Care Campus at 1 site in Israel.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 27 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01403519, which also lists 7 linked publications.
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 27 Jul 2011.