Alzheimer's DiseaseNCT00900770
Implications of Amyloid Pathology
An observational study of Alzheimer's Disease, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
The purpose of this study is to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical Alzheimer's Disease (AD). Read more about this study
- Who is it for?
- Ages 60 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Mar 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 60 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Longitudinal cohort of the Massachusetts Alzheimer's Disease Research Center and community volunteers
Who may be able to join
- Age range from 60 to 90 years
- Clinical Dementia Rating (CDR) Score of 0
- Mini Mental State Exam of 27-30
- A study partner who can answer questions pertaining to daily functioning
- Perform within 1.5 standard deviation of age and education matched norms on screening tests of attention and executive function, language, visuospatial perception and episodic memory
- Stable medications for at least 30 days
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- Fluent in English
- Modified Hachinski Score of <4
- Geriatric Depression Scale Score <10
Who cannot join
- Diagnosis of MCI or dementia
- Individuals with contraindications to MRI (i.e., implanted metal including pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes and those with a history of claustrophobia)
- Unstable medications or on medications with CNS effects including cholinesterase inhibitors, memantine, and antidepressants
- Major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder, or treatment with ECT (mild depression that is well treated with stable dose of SSRI antidepressants will be allowed)
- Multiple sclerosis or other autoimmune disorders
- Huntington's disease
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- Head injury, post-traumatic dementia or seizures
- Metabolic encephalopathy, CNS infection, hydrocephalus
- Cardiovascular disease, stroke, congestive heart failure
- Substance abuse within the past 2 years
- Active cancer
- Active hematological, renal, pulmonary, endocrine or hepatic disorders
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Kelly O'Keefe, 617-726-6212, kokeefe1@partners.org
Meghan Frey, 617-732-8085, mfrey1@partners.org
About this study
Official title: Implications of Amyloid Deposition in Clinically Normal Older Individuals
The purpose of this study is to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical Alzheimer's Disease (AD).
Read the detailed description
There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.
This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate evidence of abnormality consistent with prodromal AD.
The study will use a combination of functional, structural, and cognitive measures to detect early effects of amyloid deposition, and will utilize PIB retention in order to characterize the relationship of amyloid to neuropsychological and imaging markers of prodromal AD. The relationship of PIB retention to genetic, plasma and cerebrospinal fluid (CSF) biomarkers will be explored. These preliminary data will be used to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical AD. When completed, this project will either provide evidence that the presence of amyloid deposition is a useful biomarker for incipient AD or raise the possibility that amyloid deposition examined in isolation is insufficient to predict early symptoms and progression of AD.
- Conditions
- Alzheimer's Disease
- Keywords
- dementia, mild cognitive impairment, beta amyloid
- Medical subject headings
- Alzheimer Disease, Dementia, Cognitive Dysfunction, Plaque, Amyloid
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 |
|---|---|---|
| PIB+ NC | PIB positive, cognitively normal individuals with foci of elevated PIB retention in cortical regions typically affected in AD | |
| PIB- NC | PIB negative, cognitively normal individuals without amyloid deposition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pittsburgh Compound B (PiB) and F-18 fluorodeoxyglucose (FDG) PET Scan
Measured: at 1 month
Secondary outcomes (2)
Cognitive and functional assessments
Measured: Baseline and annually for 5 years
Lumbar Puncture (optional)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2009 (estimated)
- Study startNov 2008
- Primary completionMar 2014 (estimated)
- Study completionMar 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Reisa Sperling, MD, Principal investigator, Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00900770
- Sponsor's protocol ID
- IA0158
- Other IDs
- 2P50AG005134-268381, 2P50AG005134
- Status last verified
- Dec 2009
- First submitted
- 11 May 2009
- Last updated
- 29 Dec 2009
- Results posted
- No
Publications
Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, Grodstein F, Wright CI, Blacker D, Rosas HD, Sperling RA, Atri A, Growdon JH, Hyman BT, Morris JC, Fischl B, Buckner RL. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009 Mar;19(3):497-510. doi: 10.1093/cercor/bhn113. Epub 2008 Jul 16.
PubMed 18632739Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008 Nov;65(11):1509-17. doi: 10.1001/archneur.65.11.1509.
PubMed 19001171Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, Knopman DS, Boeve BF, Klunk WE, Mathis CA, Petersen RC. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008 Mar;131(Pt 3):665-80. doi: 10.1093/brain/awm336. Epub 2008 Feb 7.
PubMed 18263627Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006 Aug 8;67(3):446-52. doi: 10.1212/01.wnl.0000228230.26044.a4.
PubMed 16894106
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implications of Amyloid Deposition in Clinically Normal Older Individuals
- ClinicalTrials.gov ID
- NCT00900770
- Acronym / sponsor ID
- IA0158
- Conditions
- Alzheimer's Disease
- Keywords
- dementia, mild cognitive impairment, beta amyloid
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- Nov 2008
- Primary completion
- Mar 2014 (estimated)
- Study completion
- Mar 2014 (estimated)
- First posted
- 13 May 2009 (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.
The purpose of this study is to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical Alzheimer's Disease (AD).
Detailed description
There is compelling evidence supporting amyloid as one of the key pathologic agents in AD. Autopsy studies suggest the amount and location of fibrillar amyloid deposition does not relate strongly to the degree and type of clinical impairment, compared to tau pathology and neuronal loss. A substantial percentage of individuals known to be cognitively intact prior to death demonstrate significant amyloid pathology at autopsy. PIB-PET studies of older normal individuals have also demonstrated significant amyloid deposition in substantial percentages.
This study will test the hypothesis that amyloid is associated with synaptic dysfunction and neuronal damage. While some individuals are able to compensate for amyloid-related toxicity for an extended time period, sensitive imaging and neuropsychological markers will reveal that normal subjects with evidence of high amyloid burden do demonstrate evidence of abnormality consistent with prodromal AD.
The study will use a combination of functional, structural, and cognitive measures to detect early effects of amyloid deposition, and will utilize PIB retention in order to characterize the relationship of amyloid to neuropsychological and imaging markers of prodromal AD. The relationship of PIB retention to genetic, plasma and cerebrospinal fluid (CSF) biomarkers will be explored. These preliminary data will be used to determine whether asymptomatic older individuals with high amyloid burden will subsequently manifest cognitive impairment and eventually progress to clinical AD. When completed, this project will either provide evidence that the presence of amyloid deposition is a useful biomarker for incipient AD or raise the possibility that amyloid deposition examined in isolation is insufficient to predict early symptoms and progression of AD.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PIB+ NC | – | –PIB positive, cognitively normal individuals with foci of elevated PIB retention in cortical regions typically affected in AD |
| PIB- NC | – | –PIB negative, cognitively normal individuals without amyloid deposition |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Longitudinal cohort of the Massachusetts Alzheimer's Disease Research Center and community volunteers
Key inclusion criteria (9 listed)
- Age range from 60 to 90 years
- Clinical Dementia Rating (CDR) Score of 0
- Mini Mental State Exam of 27-30
- A study partner who can answer questions pertaining to daily functioning
- Perform within 1.5 standard deviation of age and education matched norms on screening tests of attention and executive function, language, visuospatial perception and episodic memory
Key exclusion criteria (12 listed)
- Diagnosis of MCI or dementia
- Individuals with contraindications to MRI (i.e., implanted metal including pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes and those with a history of claustrophobia)
- Unstable medications or on medications with CNS effects including cholinesterase inhibitors, memantine, and antidepressants
- Major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder, or treatment with ECT (mild depression that is well treated with stable dose of SSRI antidepressants will be allowed)
- Multiple sclerosis or other autoimmune disorders
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
Pittsburgh Compound B (PiB) and F-18 fluorodeoxyglucose (FDG) PET Scan
Time frame: at 1 month
2 secondary outcomes
Cognitive and functional assessments
Time frame: Baseline and annually for 5 years
Lumbar Puncture (optional)
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2009.
- Background: PubMed 18632739Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, Grodstein F, Wright CI, Blacker D, Rosas HD, Sperling RA, Atri A, Growdon JH, Hyman BT, Morris JC, Fischl B, Buckner RL. The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009 Mar;19(3):497-510. doi: 10.1093/cercor/bhn113. Epub 2008 Jul 16.
- Background: PubMed 19001171Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008 Nov;65(11):1509-17. doi: 10.1001/archneur.65.11.1509.
- Background: PubMed 18263627Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, Knopman DS, Boeve BF, Klunk WE, Mathis CA, Petersen RC. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008 Mar;131(Pt 3):665-80. doi: 10.1093/brain/awm336. Epub 2008 Feb 7.
- Background: PubMed 16894106Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006 Aug 8;67(3):446-52. doi: 10.1212/01.wnl.0000228230.26044.a4.
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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.
Reisa Sperling, MD principal investigator
Director of Clinical Research, Memory Disorders Unit, Brigham and Women's Hospital
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 National Institute on Aging (NIA) at 1 site in United States.
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 9 inclusion and 12 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 29 Dec 2009. 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 United States. 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.
What does the primary outcome measure?
Pittsburgh Compound B (PiB) and F-18 fluorodeoxyglucose (FDG) PET Scan (time frame: at 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00900770, which also lists 4 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 29 Dec 2009.