Drug ResistanceNCT01386476
(18F)FCWAY and the Blood-Brain Barrier
An observational study of Drug Resistance, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: The blood-brain barrier helps protect the brain from infections and toxins in the blood stream. But it can also prevent certain drugs from reaching the brain to treat diseases or other problems. Researchers are interested in chemicals that will help show how the barrier works. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Resistance
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2011to 1 Sep 2016
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be 18 to 50 years old.
- Subjects must be currently healthy, based on history, physical exam, and laboratory testing.
- With the exception of birth control pills, subjects must agree not to take any medication, prescription or over-the-counter, one week before and one week after receiving tariquidar.
- Subjects must be able and willing to give written informed consent.
Who cannot join
- Subjects routinely taking prescription medications, except birth control pills. That is, subjects should not discontinue mediations merely to participate in this study.
- Subjects taking recreational or over-the-counter drugs.
- Subjects will be excluded if they have any current Axis I diagnosis, including a current diagnosis of alcohol or substance abuse.
- History of psychotic symptoms or suicide attempt.
- Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes or a history of seizures, because seizures may increase the function of P-gp.
- Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
Show all 12Show fewer
- Pregnancy or breast feeding.
- Positive urine drug screen.
- Unlikely to tolerate small, enclosed spaces, as in the MRI.
- Metallic foreign bodies that would be affected by the MRI magnet or fear of enclosed spaces likely to make the subject unable to complete an MRI scan.
- Positive HIV status.
- Inability to lie flat on camera bed for about 2 (Omega) hours.
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: The Serotonin-1A Receptor Radioligand (18F)FCWAY as a Potential Substrate for Efflux Transport at the Blood-Brain Barrier
Background:
- The blood-brain barrier helps protect the brain from infections and toxins in the blood stream. But it can also prevent certain drugs from reaching the brain to treat diseases or other problems. Researchers are interested in chemicals that will help show how the barrier works. One possible chemical, (18F)FCWAY, may be useful for studying the barrier. More tests are needed to determine how effective it is.
Read more
Objectives:
- To test whether (18F)FCWAY can be used to help study the blood-brain barrier.
Eligibility:
- Healthy volunteers between 18 and 50 years of age.
Design:
- This study requires a screening visit and two scanning visits.
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
- At the first scanning visit, participants will have a magnetic resonance imaging scan to provide baseline images of the brain.
- Before the second visit, some participants will stay overnight in the hospital. They will receive the drug tariquidar, which may help the (18F)FCWAY show the blood-brain barrier more clearly.
- At the second scanning visit, all participants will have a positron emission tomography scan with (18F)FCWAY to see how well the drug shows the blood-brain barrier on the scan.
Read the detailed description
Objective:
We use the radioligand [(11)C]dLop (N-desmethyl-loperamide) in positron emission tomography (PET) studies to measure function of P-gp, an efflux transporter at the blood-brain barrier. Because [(11)C]dLop is an avid substrate for P-gp, we see almost no radioactivity in brain at baseline in healthy volunteers. However, we do see increased radioactivity in brain in some patients with dementia, or when we co-administer a medication which blocks the function of P-gp. While [(11)C]dLop is useful for detecting increased radioactivity in brain, a disadvantage of [(11)C]dLop is that it is not useful for detecting decreased radioactivity in brain. The reason for this is that we have a floor effect, where we are unable to detect less radioactivity than zero. Preclinical studies indicate that increases in P-gp activity (which would manifest as decreased radioactivity in brain) correlate with drug-resistant epilepsy and HIV. To better understand diseases associated with not only increased but also decreased P-gp activity, we wish to identify a radioligand which is a moderate substrate of P-gp. We suspect that [(18)F]FCWAY is a moderate substrate for P-gp, because some radioligand gets into brain at baseline, but more gets into brain after administering a drug (disulfiram) which inhibits P-gp. The objective of this study is to determine whether the serotonin 1A antagonist [(18)F]FCWAY is a substrate of P-gp by determining whether the P-gp inhibitor, tariquidar, increases uptake of the radioligand into brain.
Study Population:
We will study up to 45 healthy adults, ages 18-50. Participants must be free of medications, with the exception of birth control pills, as medications may confound our data. or iii patients who received a single PET scan as stated under i), will be invited back to have the option of receiving the second PET scan with tariquidar. A maximum of 15 ubjects will receive both scans.
Design:
Healthy adults will undergo either 1) a single PET scan of the brain with [(18)F]FCWAY (at baseline, or during infusion of intravenous tariquidar or 2) two PET scans (both a baseline and a tariquidar scan).
Outcome Measures:
If [(18)F]FCWAY is a substrate of P-gp, pre-treatment with tariquidar will increase its brain uptake of [(18)F]FCWAY and delay the time of peak uptake.
- Conditions
- Drug Resistance
- Keywords
- 5-HT1A Receptors, Blood Brain Barrier, Drug Resistance, Healthy Volunteer, HV
What is being measured
The primary outcome is the main question the study is designed to answer.
Tariquidar will increase uptake of 18F-FCWAY in brain
Secondary outcomes (1)
Tariquidar will delay brain peak of 18F-FCWAY
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study start15 Jun 2011
- Study completion1 Sep 2016
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 Drug ResistanceStudies 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
- Other
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386476
- Sponsor's protocol ID
- 110195
- Other IDs
- 11-M-0195
- Status last verified
- 1 Sep 2016
- First submitted
- 30 Jun 2011
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Kannan P, John C, Zoghbi SS, Halldin C, Gottesman MM, Innis RB, Hall MD. Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. Clin Pharmacol Ther. 2009 Oct;86(4):368-77. doi: 10.1038/clpt.2009.138. Epub 2009 Jul 22.
PubMed 19625998Zhang XY, Yasuno F, Zoghbi SS, Liow JS, Hong J, McCarron JA, Pike VW, Innis RB. Quantification of serotonin 5-HT1A receptors in humans with [11C](R)-(-)-RWAY: radiometabolite(s) likely confound brain measurements. Synapse. 2007 Jul;61(7):469-77. doi: 10.1002/syn.20392.
PubMed 17415792Liow JS, Lu S, McCarron JA, Hong J, Musachio JL, Pike VW, Innis RB, Zoghbi SS. Effect of a P-glycoprotein inhibitor, Cyclosporin A, on the disposition in rodent brain and blood of the 5-HT1A receptor radioligand, [11C](R)-(-)-RWAY. Synapse. 2007 Feb;61(2):96-105. doi: 10.1002/syn.20348.
PubMed 17117422
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Serotonin-1A Receptor Radioligand (18F)FCWAY as a Potential Substrate for Efflux Transport at the Blood-Brain Barrier
- ClinicalTrials.gov ID
- NCT01386476
- Acronym / sponsor ID
- 110195
- Conditions
- Drug Resistance
- Keywords
- 5-HT1A Receptors, Blood Brain Barrier, Drug Resistance, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 15 Jun 2011
- Study completion
- 1 Sep 2016
- First posted
- 1 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.
Background:
- The blood-brain barrier helps protect the brain from infections and toxins in the blood stream. But it can also prevent certain drugs from reaching the brain to treat diseases or other problems. Researchers are interested in chemicals that will help show how the barrier works. One possible chemical, (18F)FCWAY, may be useful for studying the barrier. More tests are needed to determine how effective it is.
Objectives:
- To test whether (18F)FCWAY can be used to help study the blood-brain barrier.
Eligibility:
- Healthy volunteers between 18 and 50 years of age.
Design:
- This study requires a screening visit and two scanning visits.
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
- At the first scanning visit, participants will have a magnetic resonance imaging scan to provide baseline images of the brain.
- Before the second visit, some participants will stay overnight in the hospital. They will receive the drug tariquidar, which may help the (18F)FCWAY show the blood-brain barrier more clearly.
- At the second scanning visit, all participants will have a positron emission tomography scan with (18F)FCWAY to see how well the drug shows the blood-brain barrier on the scan.
Detailed description
Objective:
We use the radioligand [(11)C]dLop (N-desmethyl-loperamide) in positron emission tomography (PET) studies to measure function of P-gp, an efflux transporter at the blood-brain barrier. Because [(11)C]dLop is an avid substrate for P-gp, we see almost no radioactivity in brain at baseline in healthy volunteers. However, we do see increased radioactivity in brain in some patients with dementia, or when we co-administer a medication which blocks the function of P-gp. While [(11)C]dLop is useful for detecting increased radioactivity in brain, a disadvantage of [(11)C]dLop is that it is not useful for detecting decreased radioactivity in brain. The reason for this is that we have a floor effect, where we are unable to detect less radioactivity than zero. Preclinical studies indicate that increases in P-gp activity (which would manifest as decreased radioactivity in brain) correlate with drug-resistant epilepsy and HIV. To better understand diseases associated with not only increased but also decreased P-gp activity, we wish to identify a radioligand which is a moderate substrate of P-gp. We suspect that [(18)F]FCWAY is a moderate substrate for P-gp, because some radioligand gets into brain at baseline, but more gets into brain after administering a drug (disulfiram) which inhibits P-gp. The objective of this study is to determine whether the serotonin 1A antagonist [(18)F]FCWAY is a substrate of P-gp by determining whether the P-gp inhibitor, tariquidar, increases uptake of the radioligand into brain.
Study Population:
We will study up to 45 healthy adults, ages 18-50. Participants must be free of medications, with the exception of birth control pills, as medications may confound our data. or iii patients who received a single PET scan as stated under i), will be invited back to have the option of receiving the second PET scan with tariquidar. A maximum of 15 ubjects will receive both scans.
Design:
Healthy adults will undergo either 1) a single PET scan of the brain with [(18)F]FCWAY (at baseline, or during infusion of intravenous tariquidar or 2) two PET scans (both a baseline and a tariquidar scan).
Outcome Measures:
If [(18)F]FCWAY is a substrate of P-gp, pre-treatment with tariquidar will increase its brain uptake of [(18)F]FCWAY and delay the time of peak uptake.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Subjects must be 18 to 50 years old.
- Subjects must be currently healthy, based on history, physical exam, and laboratory testing.
- With the exception of birth control pills, subjects must agree not to take any medication, prescription or over-the-counter, one week before and one week after receiving tariquidar.
- Subjects must be able and willing to give written informed consent.
Key exclusion criteria (12 listed)
- Subjects routinely taking prescription medications, except birth control pills. That is, subjects should not discontinue mediations merely to participate in this study.
- Subjects taking recreational or over-the-counter drugs.
- Subjects will be excluded if they have any current Axis I diagnosis, including a current diagnosis of alcohol or substance abuse.
- History of psychotic symptoms or suicide attempt.
- Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes or a history of seizures, because seizures may increase the function of P-gp.
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
Tariquidar will increase uptake of 18F-FCWAY in brain
1 secondary outcome
Tariquidar will delay brain peak of 18F-FCWAY
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 5 Jul 2018.
- Background: PubMed 19625998Kannan P, John C, Zoghbi SS, Halldin C, Gottesman MM, Innis RB, Hall MD. Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. Clin Pharmacol Ther. 2009 Oct;86(4):368-77. doi: 10.1038/clpt.2009.138. Epub 2009 Jul 22.
- Background: PubMed 17415792Zhang XY, Yasuno F, Zoghbi SS, Liow JS, Hong J, McCarron JA, Pike VW, Innis RB. Quantification of serotonin 5-HT1A receptors in humans with [11C](R)-(-)-RWAY: radiometabolite(s) likely confound brain measurements. Synapse. 2007 Jul;61(7):469-77. doi: 10.1002/syn.20392.
- Background: PubMed 17117422Liow JS, Lu S, McCarron JA, Hong J, Musachio JL, Pike VW, Innis RB, Zoghbi SS. Effect of a P-glycoprotein inhibitor, Cyclosporin A, on the disposition in rodent brain and blood of the 5-HT1A receptor radioligand, [11C](R)-(-)-RWAY. Synapse. 2007 Feb;61(2):96-105. doi: 10.1002/syn.20348.
Related trials for Drug Resistance
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
Active, not recruitingPhase 2
Response to Emerging Antimicrobial Resistance With Containment Microbiota Therapy (REACT)
Multi-Drug Resistant Organism Colonization
Active, not recruitingPhase 2
Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer
Prostate Cancer
Recruiting
Identification of Biomarkers for Vagus Nerve Stimulation in Patients With Refractory Epilepsy
Refractory Epilepsy
RecruitingPhase 3
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)
Prostate Cancer Metastatic
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.
Robert B Innis, 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 Drug Resistance, 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 4 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: finished, as of the sponsor's last update on 5 Jul 2018. 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?
Tariquidar will increase uptake of 18F-FCWAY in brain. 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 NCT01386476, 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 5 Jul 2018.