HealthyPhase 1NCT00538798
PET Imaging of Brain mGluR5 Receptors Using [18F]SP203
A Phase 1 study testing [18F]SP203 in people with Healthy and Glutamate Receptor, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
The metabotropic glutamate subtype five (mGluR5) receptor is a protein found in the brain and is the target for the excitatory chemical messenger glutimate. The purpose of this protocol is to measure mGluR5 receptors in the brain using positron emission tomography (PET) and a research drug called [18F]SP203. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Glutamate Receptor, mGlur5 Protein
- What is being tested?
- [18F]SP203
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2007to 17 Mar 2015
- Phase
- Phase 1
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy control subjects aged 18 65 years, with history/physical exam, ECG, and laboratory tests within one year of the PET scan within normal limits.
Who cannot join
- Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities.
- Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual limits.
- Pregnancy and breast feeding.
- Claustrophobia. (part 1 and 3 only)
- Presence of ferromagnetic metal in the body or heart pacemaker. (part 1 and 3 only)
- Positive HIV test.
- Consumed alcohol within 48 hours before the PET scan.
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: PET Imaging of Brain mGluR5 Receptors Using [18F]SP203 and [11C]SP203
The metabotropic glutamate subtype five (mGluR5) receptor is a protein found in the brain and is the target for the excitatory chemical messenger glutimate. The purpose of this protocol is to measure mGluR5 receptors in the brain using positron emission tomography (PET) and a research drug called [18F]SP203.
Read the detailed description
Metabotropic glutamate receptors are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. Metabotropic Glutamate receptors (mGluR5) are Group I receptors localized post-synaptically and found in several regions of the brain including the striatum, hippocampus, amygdala, and cortex. Activation of mGluR5 stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increase of intracellular Ca2+ levels. Several potent antagonists for mGluR5 have been developed, including 6 methyl-2-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4yl)ethynyl] pyridine (MTEP) however, no simple derivatives of MPEP or MTEP had proven to be useful for in vivo imaging.
In the present protocol, we will use a new PET ligand [(18)F]SP203 for two reasons: Part 1.) we will perform kinetic brain imaging to quantify mGluR5 binding parameters in brain and determine the reliability and reproducibility of these measures in 15 healthy controls Part 2.) if the tracer is proved successful in the part 1, we plan to estimate radiation-absorbed doses of [(18)F]SP203 in healthy human subjects by performing whole body imaging.
We will also use another new ligand, [11C]SP203, which has the same structure as [(18)F]SP203 but labeled with (11)C instead of (18)F. Part 3) the same purpose as part 1 but with [(11)C]SP203 instead of [(18)F]SP203. Part 4) if [(11)C]SP203 is proved successful in the part 3, we plan to estimate radiation absorbed doses of [(11)C]SP203 in healthy human subjects. At this moment, we do not plan to perform additional scans of [(18)F]SP203 under the current protocol. All future subjects will participate in scans of [(11)C]SP203.
Additionally, Part 5) we will measure the difference in [(18)F]SP203 concentration between the artery and the vein without PET scanning to assess whether the venous blood is a valid and less invasive substitute of arterial blood. In some of [(18)F]SP203 scans performed in the current protocol, we compared [(18)F]SP203 levels between radial artery and antecubital vein and observed 30% - 60% lower levels in vein. We plan to test whether sampling from a vein in the hand and / or warming up makes [(18)F]SP203 levels in vein similar to artery.
Successful development of a PET ligand to image mGluR5 will have a strong impact on clinical management of brain disorders with disruptions in glutamatergic transmission such as schizophrenia, anxiety, and neurodegenerative disorders including Alzheimer s and Parkinson s disease.
- Conditions
- Healthy, Glutamate Receptor, mGlur5 Protein, Excitatory Amino Acid Receptors, Drug Kinetics, PET Scan
- Being tested
- [18F]SP203
- Keywords
- Pharmacokinetics, Binding Potential, Glutamate, Positron Emission Tomography, Metabolic Glutamate Receptors, Healthy Volunteer, HV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]SP203Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2007 (estimated)
- Study start28 Sep 2007
- Study completion17 Mar 2015
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 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Masahiro Fujita, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00538798
- Sponsor's protocol ID
- 070082
- Other IDs
- 07-M-0082
- Status last verified
- 17 Mar 2015
- First submitted
- 2 Oct 2007
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Brodkin J, Bradbury M, Busse C, Warren N, Bristow LJ, Varney MA. Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci. 2002 Dec;16(11):2241-4. doi: 10.1046/j.1460-9568.2002.02294.x.
PubMed 12473093Cosford ND, Roppe J, Tehrani L, Schweiger EJ, Seiders TJ, Chaudary A, Rao S, Varney MA. [3H]-methoxymethyl-MTEP and [3H]-methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett. 2003 Feb 10;13(3):351-4. doi: 10.1016/s0960-894x(02)00997-6.
PubMed 12565928Fujita M, Seibyl JP, Verhoeff NP, Ichise M, Baldwin RM, Zoghbi SS, Burger C, Staley JK, Rajeevan N, Charney DS, Innis RB. Kinetic and equilibrium analyses of [(123)I]epidepride binding to striatal and extrastriatal dopamine D(2) receptors. Synapse. 1999 Dec 15;34(4):290-304. doi: 10.1002/(SICI)1098-2396(19991215)34:43.0.CO;2-B.
PubMed 10529723
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
- PET Imaging of Brain mGluR5 Receptors Using [18F]SP203 and [11C]SP203
- ClinicalTrials.gov ID
- NCT00538798
- Acronym / sponsor ID
- 070082
- Conditions
- Healthy, Glutamate Receptor, mGlur5 Protein, Excitatory Amino Acid Receptors, Drug Kinetics, PET Scan
- Keywords
- Pharmacokinetics, Binding Potential, Glutamate, Positron Emission Tomography, Metabolic Glutamate Receptors, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 28 Sep 2007
- Study completion
- 17 Mar 2015 (actual)
- First posted
- 3 Oct 2007 (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 metabotropic glutamate subtype five (mGluR5) receptor is a protein found in the brain and is the target for the excitatory chemical messenger glutimate. The purpose of this protocol is to measure mGluR5 receptors in the brain using positron emission tomography (PET) and a research drug called [18F]SP203.
Detailed description
Metabotropic glutamate receptors are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. Metabotropic Glutamate receptors (mGluR5) are Group I receptors localized post-synaptically and found in several regions of the brain including the striatum, hippocampus, amygdala, and cortex. Activation of mGluR5 stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increase of intracellular Ca2+ levels. Several potent antagonists for mGluR5 have been developed, including 6 methyl-2-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4yl)ethynyl] pyridine (MTEP) however, no simple derivatives of MPEP or MTEP had proven to be useful for in vivo imaging.
In the present protocol, we will use a new PET ligand [(18)F]SP203 for two reasons: Part 1.) we will perform kinetic brain imaging to quantify mGluR5 binding parameters in brain and determine the reliability and reproducibility of these measures in 15 healthy controls Part 2.) if the tracer is proved successful in the part 1, we plan to estimate radiation-absorbed doses of [(18)F]SP203 in healthy human subjects by performing whole body imaging.
We will also use another new ligand, [11C]SP203, which has the same structure as [(18)F]SP203 but labeled with (11)C instead of (18)F. Part 3) the same purpose as part 1 but with [(11)C]SP203 instead of [(18)F]SP203. Part 4) if [(11)C]SP203 is proved successful in the part 3, we plan to estimate radiation absorbed doses of [(11)C]SP203 in healthy human subjects. At this moment, we do not plan to perform additional scans of [(18)F]SP203 under the current protocol. All future subjects will participate in scans of [(11)C]SP203.
Additionally, Part 5) we will measure the difference in [(18)F]SP203 concentration between the artery and the vein without PET scanning to assess whether the venous blood is a valid and less invasive substitute of arterial blood. In some of [(18)F]SP203 scans performed in the current protocol, we compared [(18)F]SP203 levels between radial artery and antecubital vein and observed 30% - 60% lower levels in vein. We plan to test whether sampling from a vein in the hand and / or warming up makes [(18)F]SP203 levels in vein similar to artery.
Successful development of a PET ligand to image mGluR5 will have a strong impact on clinical management of brain disorders with disruptions in glutamatergic transmission such as schizophrenia, anxiety, and neurodegenerative disorders including Alzheimer s and Parkinson s disease.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy control subjects aged 18 65 years, with history/physical exam, ECG, and laboratory tests within one year of the PET scan within normal limits.
Key exclusion criteria (8 listed)
- Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.
- Laboratory tests with clinically significant abnormalities.
- Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual limits.
- Pregnancy and breast feeding.
- Claustrophobia. (part 1 and 3 only)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]SP203 | Drug | – |
Primary outcome
Not reported in the source record.
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 12473093Brodkin J, Bradbury M, Busse C, Warren N, Bristow LJ, Varney MA. Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci. 2002 Dec;16(11):2241-4. doi: 10.1046/j.1460-9568.2002.02294.x.
- Background: PubMed 12565928Cosford ND, Roppe J, Tehrani L, Schweiger EJ, Seiders TJ, Chaudary A, Rao S, Varney MA. [3H]-methoxymethyl-MTEP and [3H]-methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett. 2003 Feb 10;13(3):351-4. doi: 10.1016/s0960-894x(02)00997-6.
- Background: PubMed 10529723Fujita M, Seibyl JP, Verhoeff NP, Ichise M, Baldwin RM, Zoghbi SS, Burger C, Staley JK, Rajeevan N, Charney DS, Innis RB. Kinetic and equilibrium analyses of [(123)I]epidepride binding to striatal and extrastriatal dopamine D(2) receptors. Synapse. 1999 Dec 15;34(4):290-304. doi: 10.1002/(SICI)1098-2396(19991215)34:43.0.CO;2-B.
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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.
Masahiro Fujita, 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?
A Phase 1 study testing [18F]SP203 in people with Healthy and Glutamate Receptor, 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 1 inclusion and 8 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00538798, 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.