HealthyNCT00605254
PET Imaging of P-glycoprotein Function Using [11C]dLop
An observational study of Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will test the use of a radioactive substance called [11C]dLop for measuring P-glycoprotein (P-gp) using positron emission tomography (PET) imaging. The P-gp protein acts as a pump in cells, affecting a variety of functions, such as limiting drug absorption and elimination and decreasing drug penetration… Read more about this study
- Who is it for?
- Ages 18 to 51 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2008to 4 Sep 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 18 to 51 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients with the diagnosis of probable Alzheimer disease. All patients must meet capacity criteria to consent to research (see Consent documents and process).
- Healthy volunteers.
Who cannot join
- Current psychiatric disease, illicit substance use, or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT less than or equal to 1.5 times the upper limit of normal.
- 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 HIV test.
- Positive result on urine screen for illicit drugs.
Show all 11Show fewer
- You cannot lie on your back for extended periods of time.
- Use of blood-thinning medications (such as warfarin; aspirin is allowed), current or prior history of coagulopathy. This will be necessary only for subjects who have arterial catheter placement.
- History of neurological disease other than Alzheimer disease.
- For oral tariquidar dose-escalation study: Subjects taking medications other than birth control pills.
- For Alzheimer s disease patients and age-matched volunteers: Subjects taking medications that are known substrates of P-gp that cannot be safely discontinued for this study.
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: Brain and Whole Body Imaging of P-Glycoprotein Function Using [11C]dLop
This study will test the use of a radioactive substance called [11C]dLop for measuring P-glycoprotein (P-gp) using positron emission tomography (PET) imaging. The P-gp protein acts as a pump in cells, affecting a variety of functions, such as limiting drug absorption and elimination and decreasing drug penetration into certain tissues, such as the brain. It is a major obstacle to successful chemotherapy because it can pump cancer drugs out of the cells, interfering with treatment. Decreased P-gp function may contribute to disorders such as Parkinson s disease and Alzheimer s disease, whereas higher levels of the protein have been found in patients with epilepsy and in several forms of drug-resistant cancer tumors. This study will determine uptake and clearance of [11C]dLop and the radiation exposure to organs of the body to assess its possible use in further studies of P-gp function.
Healthy normal volunteers between 18 and 51 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination and blood and urine tests.
Read more
Participants undergo the following procedures:
- Electrocardiogram (ECG): A test of the electrical function of the heart.
- Brain PET scans: PET imaging 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. The tracer used in this study is [18F]FMPEP-d(2). Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer and another catheter is placed in an artery in the wrist to obtain blood samples during the scan. For the procedure, the subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed to help keep the person s head still during the scan so the images will be clear. A brief scan is done just before the tracer is injected to provide measures of the brain that are helpful in calculating information from subsequent scans. After the tracer is injected, pictures are taken for about 2.5 hours, while the subject lies still on the scanner bed. Blood and urine tests are done after 24 hours after the scan.
- Magnetic resonance imaging (MRI): An MRI scan is done within 1 year (before or after) of the PET scan. This procedure uses a magnetic field and radio waves to produce images of the brain. The subject lies on a table that is moved into the scanner (a tube-like device), wearing earplugs to muffle the noise of the machine during the scanning process. The test takes about 1 hour....
Read the detailed description
P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter and is the major efflux pump in the blood-brain barrier. P-gp has several physiological roles such as limiting drug absorption, active drug elimination, and limits drug penetration into sensitive tissues (e.g., brain and testis) (Fromm, 2004). Reduced activity or expression of P-gp may contribute to neurodegenerative disorders such as Parkinson s and Alzheimer s disease. The reduced activity of P-gp (i.e., decreased neuroprotection at the blood brain barrier) may allow harmful pesticides access to the brain which can damage the brain s dopaminergic cell groups possibly leading to Parkinson s disease (Betarbet et al., 2000; Kortekaas et al., 2005). The increased deposition of beta-amyloid in Alzheimer s disease, may be due in part, to the decreased elimination of cerebral beta-amyloid in brain (Vogelgesang et al., 2002). Conversely, an overexpression of P-gp has been found in epilepsy and in several forms of multi drug resistant cancer tumors (Brandt et al., 2006; Szakacs et al., 2006). In vivo evaluation of P-gp function in the brain and throughout the body is important in disease states, and in therapeutic and diagnostic drug evaluation.
P-gp function has been assessed in healthy volunteers with positron emission tomography (PET) using [11C]verapamil, nevertheless, accurate quantification of this PET radioligand is difficult due to the large contribution of radiometabolites and low signal (Ikoma et al., 2006; Lee et al., 2006; Lubberink et al., 2007). Therefore, we have recently developed [11C]dLop as an alternative radioligand for imaging P-gp function, which will allow a more accurate quantification of P-gp with a higher signal and less contribution of radiometabolites. In the current protocol, we wish to evaluate [11C]dLop in healthy volunteers to determine the kinetics of brain imaging of P-gp function. In order to simulate P-gp dysfunction in healthy volunteers we will administer the P-gp inhibitor tariquidar. We will perform brain PET scans using [11C]dLop before and after P-gp blockade in order to quantify P-gp function at the blood-brain barrier.
- Conditions
- Healthy
- Keywords
- P-Glycoprotein, Positron Emission Tomography, Blood Brain Barrier, Quantitative Imaging, Multi-Drug Transporter, Healthy Volunteer, HV
What is being measured
The primary outcome is the main question the study is designed to answer.
PET
Measured: continuous
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2008 (estimated)
- Study start24 Jan 2008
- Study completion4 Sep 2014
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 HealthyStudies 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
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 58 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
- NCT00605254
- Sponsor's protocol ID
- 080062
- Other IDs
- 08-M-0062
- Status last verified
- 4 Sep 2014
- First submitted
- 26 Jan 2008
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Awouters F, Niemegeers CJ, Janssen PA. Pharmacology of antidiarrheal drugs. Annu Rev Pharmacol Toxicol. 1983;23:279-301. doi: 10.1146/annurev.pa.23.040183.001431. No abstract available.
PubMed 6307123Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000 Dec;3(12):1301-6. doi: 10.1038/81834.
PubMed 11100151Bigott HM, Prior JL, Piwnica-Worms DR, Welch MJ. Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi. Mol Imaging. 2005 Jan-Mar;4(1):30-9. doi: 10.1162/15353500200504166.
PubMed 15967124Kreisl WC, Bhatia R, Morse CL, Woock AE, Zoghbi SS, Shetty HU, Pike VW, Innis RB. Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar. J Nucl Med. 2015 Jan;56(1):82-7. doi: 10.2967/jnumed.114.146894. Epub 2014 Dec 11.
PubMed 25500831
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain and Whole Body Imaging of P-Glycoprotein Function Using [11C]dLop
- ClinicalTrials.gov ID
- NCT00605254
- Acronym / sponsor ID
- 080062
- Conditions
- Healthy
- Keywords
- P-Glycoprotein, Positron Emission Tomography, Blood Brain Barrier, Quantitative Imaging, Multi-Drug Transporter, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 24 Jan 2008
- Study completion
- 4 Sep 2014
- First posted
- 31 Jan 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 test the use of a radioactive substance called [11C]dLop for measuring P-glycoprotein (P-gp) using positron emission tomography (PET) imaging. The P-gp protein acts as a pump in cells, affecting a variety of functions, such as limiting drug absorption and elimination and decreasing drug penetration into certain tissues, such as the brain. It is a major obstacle to successful chemotherapy because it can pump cancer drugs out of the cells, interfering with treatment. Decreased P-gp function may contribute to disorders such as Parkinson s disease and Alzheimer s disease, whereas higher levels of the protein have been found in patients with epilepsy and in several forms of drug-resistant cancer tumors. This study will determine uptake and clearance of [11C]dLop and the radiation exposure to organs of the body to assess its possible use in further studies of P-gp function.
Healthy normal volunteers between 18 and 51 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination and blood and urine tests.
Participants undergo the following procedures:
- Electrocardiogram (ECG): A test of the electrical function of the heart.
- Brain PET scans: PET imaging 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. The tracer used in this study is [18F]FMPEP-d(2). Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer and another catheter is placed in an artery in the wrist to obtain blood samples during the scan. For the procedure, the subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed to help keep the person s head still during the scan so the images will be clear. A brief scan is done just before the tracer is injected to provide measures of the brain that are helpful in calculating information from subsequent scans. After the tracer is injected, pictures are taken for about 2.5 hours, while the subject lies still on the scanner bed. Blood and urine tests are done after 24 hours after the scan.
- Magnetic resonance imaging (MRI): An MRI scan is done within 1 year (before or after) of the PET scan. This procedure uses a magnetic field and radio waves to produce images of the brain. The subject lies on a table that is moved into the scanner (a tube-like device), wearing earplugs to muffle the noise of the machine during the scanning process. The test takes about 1 hour....
Detailed description
P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter and is the major efflux pump in the blood-brain barrier. P-gp has several physiological roles such as limiting drug absorption, active drug elimination, and limits drug penetration into sensitive tissues (e.g., brain and testis) (Fromm, 2004). Reduced activity or expression of P-gp may contribute to neurodegenerative disorders such as Parkinson s and Alzheimer s disease. The reduced activity of P-gp (i.e., decreased neuroprotection at the blood brain barrier) may allow harmful pesticides access to the brain which can damage the brain s dopaminergic cell groups possibly leading to Parkinson s disease (Betarbet et al., 2000; Kortekaas et al., 2005). The increased deposition of beta-amyloid in Alzheimer s disease, may be due in part, to the decreased elimination of cerebral beta-amyloid in brain (Vogelgesang et al., 2002). Conversely, an overexpression of P-gp has been found in epilepsy and in several forms of multi drug resistant cancer tumors (Brandt et al., 2006; Szakacs et al., 2006). In vivo evaluation of P-gp function in the brain and throughout the body is important in disease states, and in therapeutic and diagnostic drug evaluation.
P-gp function has been assessed in healthy volunteers with positron emission tomography (PET) using [11C]verapamil, nevertheless, accurate quantification of this PET radioligand is difficult due to the large contribution of radiometabolites and low signal (Ikoma et al., 2006; Lee et al., 2006; Lubberink et al., 2007). Therefore, we have recently developed [11C]dLop as an alternative radioligand for imaging P-gp function, which will allow a more accurate quantification of P-gp with a higher signal and less contribution of radiometabolites. In the current protocol, we wish to evaluate [11C]dLop in healthy volunteers to determine the kinetics of brain imaging of P-gp function. In order to simulate P-gp dysfunction in healthy volunteers we will administer the P-gp inhibitor tariquidar. We will perform brain PET scans using [11C]dLop before and after P-gp blockade in order to quantify P-gp function at the blood-brain barrier.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 51 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Patients with the diagnosis of probable Alzheimer disease. All patients must meet capacity criteria to consent to research (see Consent documents and process).
- Healthy volunteers.
Key exclusion criteria (11 listed)
- Current psychiatric disease, illicit substance use, or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT less than or equal to 1.5 times the upper limit of normal.
- 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 HIV test.
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
PET
Time frame: continuous
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 17 Dec 2019.
- Background: PubMed 6307123Awouters F, Niemegeers CJ, Janssen PA. Pharmacology of antidiarrheal drugs. Annu Rev Pharmacol Toxicol. 1983;23:279-301. doi: 10.1146/annurev.pa.23.040183.001431. No abstract available.
- Background: PubMed 11100151Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000 Dec;3(12):1301-6. doi: 10.1038/81834.
- Background: PubMed 15967124Bigott HM, Prior JL, Piwnica-Worms DR, Welch MJ. Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi. Mol Imaging. 2005 Jan-Mar;4(1):30-9. doi: 10.1162/15353500200504166.
- Derived from this study: PubMed 25500831Kreisl WC, Bhatia R, Morse CL, Woock AE, Zoghbi SS, Shetty HU, Pike VW, Innis RB. Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar. J Nucl Med. 2015 Jan;56(1):82-7. doi: 10.2967/jnumed.114.146894. Epub 2014 Dec 11.
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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 Healthy, 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 11 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 17 Dec 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?
PET (time frame: continuous). 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 NCT00605254, 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 17 Dec 2019.