Alzheimer DiseaseNCT00677885
P-glycoprotein Function in Brain Diseases
An observational study of Alzheimer Disease and Parkinson Disease, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will measure the function of a protein called P-glycoprotein (P-gp), which is found at the blood-brain barrier, a membrane that normally prevents toxic material from entering the brain. Impaired P-gp function may allow toxins to enter the brain and cause some people to develop certain brain diseases. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Alzheimer Disease, Parkinson Disease, Frontotemporal Lobar Degeneration
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2008to 25 Aug 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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with the diagnosis of probable Alzheimer disease, Parkinson disease, or frontotemporal dementia. All patients must either meet capacity criteria to consent to research, or be able to assign a surrogate decision-maker who is able to consent to research on the subject s behalf.
- Healthy volunteers.
Who cannot join
- Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities.
- Subjects on blood-thinning medications, having coagulation disorders, or clinically significant abnormal blood clotting test (PT/PTT).
- Prior participation in other research protocols or clinical care in the last year such that radiation exposure, including that from this protocol, would exceed the guidelines set by the Radiation Safety Committee (RSC).
- Pregnancy or breast feeding.
- Positive result on urine screen for illicit drugs.
Show all 10Show fewer
- Subjects who cannot lie on their back for extended periods of time.
- History of neurological disease other than Alzheimer disease, Parkinson disease, or frontotemporal dementia.
- Subjects who have a cardiac pacemaker or metal in their body.
- Subjects taking cyclosporine A.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Measurement of P-Glycoprotein Function in Alzheimer Disease, Parkinson Disease, and Frontotemporal Dementia Using Positron Emission Tomography
This study will measure the function of a protein called P-glycoprotein (P-gp), which is found at the blood-brain barrier, a membrane that normally prevents toxic material from entering the brain. Impaired P-gp function may allow toxins to enter the brain and cause some people to develop certain brain diseases.
Healthy subjects and people with Alzheimer s disease, Parkinson s disease or frontotemporal dementia who are 35 years of age or older and in overall good health may be eligible for this study.
Read more
Participants undergo the following procedures during three outpatient visits to the NIH Clinical Center:
- Medical history, psychological evaluation, physical examination and blood and urine tests, including tests for illegal and addictive drugs.
- PET scan: This test uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain so the activity can be seen with a special camera. Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer. The subject lies on the scanner bed, with a special mask fitted to the head and attached to the bed to help keep the head still during the scan so the images obtained are clear. A brief initial scan is done to calibrate the scanner. Then, a radioactive tracer called [(15)O]H(2)O is injected into the catheter and the PET camera takes pictures of blood flow to the brain for about 60 seconds. Next, another tracer, [(11)C]dLop, is injected into the catheter and pictures are taken for about 2 hours to determine how much of this tracer is allowed to enter the brain.
- Magnetic resonance imaging (MRI): This procedure is done within 1 year (before or after) the PET scan. MRI uses a magnetic field and radio waves to produce images of the brain. For this procedure, the patient lies on a table that can slide in and out of the scanner (a tube-like device), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scan.
Read the detailed description
Objective
Alzheimer disease (AD), Parkinson disease (PD), and frontotemporal dementia (FTD) are associated with the accumulation of neurotoxic material in the brain. Potentially toxic material is normally restricted from the brain by P-glycoprotein, a transporter protein expressed by endothelial cells at the blood-brain barrier. Disruption of the blood-brain barrier has been reported in animal models of AD, PD, and FTD, and specific dysfunction of P-gp has been linked to AD and PD pathology. Therefore, P-gp may be protective against certain neurodegenerative diseases, and P-gp dysfunction may be a risk factor for developing AD, PD, or FTD.
Positron emission tomography (PET) imaging can measure P-gp function. If P-gp function is abnormal, a radiolabeled P-gp substrate will cross the blood-brain barrier and enter the brain. Intact P-gp function, on the other hand, will prevent the substrate from entering the brain. If P-gp dysfunction is a risk factor for developing AD, PD, or FTD, then patients with these diseases should have more radiolabeled substrate in the brain than healthy controls.
We have developed a novel radioligand, [(11)C]N-desmethyl-loperamide [(11)C]dLop), which is a P-gp substrate. Our goal is to use PET imaging with [(11)C]dLop to see if P-gp function is reduced in AD, PD, and FTD.
Study population
In this protocol, we wish to evaluate 15 patients with AD, 15 patients with PD, 15 patients with FTD, and 15 healthy volunteers.
Design
Subjects will undergo screening with a history, physical exam, ECG, and blood and urine laboratory testing. Subjects will receive a dedicated brain PET with [(11)C]dLop and a brain MRI. Since [11C]dLop uptake is influenced by blood flow, a [(15)O]H2O PET scan will be performed to determine flow to the brain.
Outcome measures
Our outcome measure will be the amount of [(11)C]dLop uptake in the brain in AD, PD, and FTD patients and in healthy controls. Brain uptake will be measured as the percent standardized uptake value (%SUV). Percent SUV reflects the measured brain radioactivity after [(11)C]dLop injection, corrected for patient weight and the injected dose of [(11)C]dLop. As an exploratory outcome measure, we also will correct brain uptake for cerebral blood flow. Blood flow will be determined using [(15)O]H2O PET.
- Keywords
- Alzheimer Disease, Parkinson's Disease, Frontotemporal Dementia, PET Imaging, AD, Parkinson Disease, PD
- Medical subject headings
- Alzheimer Disease, Parkinson Disease, Frontotemporal Lobar Degeneration, Frontotemporal Dementia
What is being measured
The primary outcome is the main question the study is designed to answer.
P-gp function in AD, PD, and FTD patients and in healthy volunteers. P-gp function will be determined by calculating the brain uptake of [11C]dLop
Secondary outcomes (1)
Comparing P-gp function with the severity of disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2008 (estimated)
- Study start9 May 2008
- Study completion25 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- 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
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- William C Kreisl, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00677885
- Sponsor's protocol ID
- 080124
- Other IDs
- 08-M-0124
- Status last verified
- 25 Aug 2014
- First submitted
- 13 May 2008
- Last updated
- 22 Nov 2019
- Results posted
- No
Publications
Hochman JH, Pudvah N, Qiu J, Yamazaki M, Tang C, Lin JH, Prueksaritanont T. Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm Res. 2004 Sep;21(9):1686-91. doi: 10.1023/b:pham.0000041466.84653.8c.
PubMed 15497697Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. doi: 10.1124/jpet.102.039255.
PubMed 12438524Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J. Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. doi: 10.1021/jm021012t.
PubMed 12699389
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of P-Glycoprotein Function in Alzheimer Disease, Parkinson Disease, and Frontotemporal Dementia Using Positron Emission Tomography
- ClinicalTrials.gov ID
- NCT00677885
- Acronym / sponsor ID
- 080124
- Keywords
- Alzheimer Disease, Parkinson's Disease, Frontotemporal Dementia, PET Imaging, AD, Parkinson Disease, PD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 9 May 2008
- Study completion
- 25 Aug 2014
- First posted
- 15 May 2008 (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.
This study will measure the function of a protein called P-glycoprotein (P-gp), which is found at the blood-brain barrier, a membrane that normally prevents toxic material from entering the brain. Impaired P-gp function may allow toxins to enter the brain and cause some people to develop certain brain diseases.
Healthy subjects and people with Alzheimer s disease, Parkinson s disease or frontotemporal dementia who are 35 years of age or older and in overall good health may be eligible for this study.
Participants undergo the following procedures during three outpatient visits to the NIH Clinical Center:
- Medical history, psychological evaluation, physical examination and blood and urine tests, including tests for illegal and addictive drugs.
- PET scan: This test uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain so the activity can be seen with a special camera. Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer. The subject lies on the scanner bed, with a special mask fitted to the head and attached to the bed to help keep the head still during the scan so the images obtained are clear. A brief initial scan is done to calibrate the scanner. Then, a radioactive tracer called [(15)O]H(2)O is injected into the catheter and the PET camera takes pictures of blood flow to the brain for about 60 seconds. Next, another tracer, [(11)C]dLop, is injected into the catheter and pictures are taken for about 2 hours to determine how much of this tracer is allowed to enter the brain.
- Magnetic resonance imaging (MRI): This procedure is done within 1 year (before or after) the PET scan. MRI uses a magnetic field and radio waves to produce images of the brain. For this procedure, the patient lies on a table that can slide in and out of the scanner (a tube-like device), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scan.
Detailed description
Objective
Alzheimer disease (AD), Parkinson disease (PD), and frontotemporal dementia (FTD) are associated with the accumulation of neurotoxic material in the brain. Potentially toxic material is normally restricted from the brain by P-glycoprotein, a transporter protein expressed by endothelial cells at the blood-brain barrier. Disruption of the blood-brain barrier has been reported in animal models of AD, PD, and FTD, and specific dysfunction of P-gp has been linked to AD and PD pathology. Therefore, P-gp may be protective against certain neurodegenerative diseases, and P-gp dysfunction may be a risk factor for developing AD, PD, or FTD.
Positron emission tomography (PET) imaging can measure P-gp function. If P-gp function is abnormal, a radiolabeled P-gp substrate will cross the blood-brain barrier and enter the brain. Intact P-gp function, on the other hand, will prevent the substrate from entering the brain. If P-gp dysfunction is a risk factor for developing AD, PD, or FTD, then patients with these diseases should have more radiolabeled substrate in the brain than healthy controls.
We have developed a novel radioligand, [(11)C]N-desmethyl-loperamide [(11)C]dLop), which is a P-gp substrate. Our goal is to use PET imaging with [(11)C]dLop to see if P-gp function is reduced in AD, PD, and FTD.
Study population
In this protocol, we wish to evaluate 15 patients with AD, 15 patients with PD, 15 patients with FTD, and 15 healthy volunteers.
Design
Subjects will undergo screening with a history, physical exam, ECG, and blood and urine laboratory testing. Subjects will receive a dedicated brain PET with [(11)C]dLop and a brain MRI. Since [11C]dLop uptake is influenced by blood flow, a [(15)O]H2O PET scan will be performed to determine flow to the brain.
Outcome measures
Our outcome measure will be the amount of [(11)C]dLop uptake in the brain in AD, PD, and FTD patients and in healthy controls. Brain uptake will be measured as the percent standardized uptake value (%SUV). Percent SUV reflects the measured brain radioactivity after [(11)C]dLop injection, corrected for patient weight and the injected dose of [(11)C]dLop. As an exploratory outcome measure, we also will correct brain uptake for cerebral blood flow. Blood flow will be determined using [(15)O]H2O PET.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with the diagnosis of probable Alzheimer disease, Parkinson disease, or frontotemporal dementia. All patients must either meet capacity criteria to consent to research, or be able to assign a surrogate decision-maker who is able to consent to research on the subject s behalf.
- Healthy volunteers.
Key exclusion criteria (10 listed)
- Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities.
- Subjects on blood-thinning medications, having coagulation disorders, or clinically significant abnormal blood clotting test (PT/PTT).
- Prior participation in other research protocols or clinical care in the last year such that radiation exposure, including that from this protocol, would exceed the guidelines set by the Radiation Safety Committee (RSC).
- Pregnancy or breast feeding.
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
P-gp function in AD, PD, and FTD patients and in healthy volunteers. P-gp function will be determined by calculating the brain uptake of [11C]dLop
1 secondary outcome
Comparing P-gp function with the severity of disease
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Background: PubMed 15497697Hochman JH, Pudvah N, Qiu J, Yamazaki M, Tang C, Lin JH, Prueksaritanont T. Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm Res. 2004 Sep;21(9):1686-91. doi: 10.1023/b:pham.0000041466.84653.8c.
- Background: PubMed 12438524Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. doi: 10.1124/jpet.102.039255.
- Background: PubMed 12699389Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J. Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. doi: 10.1021/jm021012t.
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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.
William C Kreisl, M.D. principal investigator
National Institute of Mental Health (NIMH)
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 Disease and Parkinson Disease, run by National Institute of Mental Health (NIMH) 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 2 inclusion and 10 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 22 Nov 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
P-gp function in AD, PD, and FTD patients and in healthy volunteers. P-gp function will be determined by calculating the brain uptake of [11C]dLop. 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 NCT00677885, which also lists 3 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 22 Nov 2019.