BaselinePhase 1NCT02181582
Specific PET Radioligand Binding to Translocator Protein
A Phase 1 study testing Emapunil and PET in people with Baseline and Blocking Receptor Binding, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: A brain protein called translocator protein (TSPO) shows changes in some brain diseases. A radioactive drug called 11C-(R)-PK 11195 is used to take pictures of TSPO using a camera called positron emission tomography (PET). Researchers want to find out how well 11C-(R)-PK 11195 takes the pictures. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Baseline, Blocking Receptor Binding
- What is being tested?
- Emapunil and PET
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jun 2014to 23 Nov 2016
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female subjects between 18 to 55 yrs of age and able to give written informed consent.
- Subjects must be healthy based on medical history, physical examination and laboratory testing.
- Be able to provide own consent.
- Agree to use contraception for 30 days after emapunil administration.
Who cannot join
- Any past or present Axis I psychiatric disorder. Any history of alcohol or substance dependence, except nicotine dependence, within the past 6 months
- Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, or serious cardiopulmonary disease.
- Active seizure disorder, as defined as having had a seizure in the past year or being on antiepileptic medications for seizures.
- Positive HIV test.
- Recent research-related exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
- Metallic foreign bodies that would be affected by the MRI magnet or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.
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- Claustrophobia
- Positive urine drug screen at time of enrollment.
- Pregnancy at time of scan (beta-HCG will be measured in all female patients within 24 hours before start of scan and must be negative). Lactating women who are breast feeding.
- Prescription or over-the counter medication use; psychotropic herb use (e.g., St. John s Wort).
- Are not able to comfortably lie flat on the back for at least two and a half hours at a time
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: Evaluation of Specific PET Radioligand Binding To Translocator Protein
Background:
- A brain protein called translocator protein (TSPO) shows changes in some brain diseases. A radioactive drug called 11C-(R)-PK 11195 is used to take pictures of TSPO using a camera called positron emission tomography (PET). Researchers want to find out how well 11C-(R)-PK 11195 takes the pictures.
Read more
Objective:
- To evaluate the radioactive chemical 11C-(R)-PK 11195.
Eligibility:
- Healthy volunteers ages 18-55.
Design:
- Participants will be screened with a medical exam.
- Participants will have scans at up to 4 visits.
- PET scan using 11C-(R)-PK 11195:
- A small tube (catheter) will be put into an artery at the wrist or elbow, by a needle. The needle will be removed, leaving only the catheter in the artery. Blood samples will be taken through this catheter.
- Another catheter will be placed into a vein in the arm or hand.
- 11C-(R)-PK 11195 will be injected through the second catheter.
- The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of it. They may get a plastic mask for their face and head.
- Participants will receive a dose of emapunil by mouth. Participants will then have another PET scan.
- Participants may have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that can slide in and out of the cylinder. Participants will get earplugs for the loud knocking noises.
- After each scan, participants will get a follow-up phone call. Two to seven days after taking emapunil, participants will return for a follow-up visit.
Read the detailed description
Objective:
The 18kDa Translocator Protein (TSPO, formerly known as the peripheral benzodiazepine receptor (PBR)) is expressed in activated microglia and reactive astrocyte. It has therefore been used as an imaging target for positron emission tomography (PET) to investigate diseases involving microglial activation and/or macrophage recruitment, such as multiple sclerosis, herpes encephalitis, Parkinson s disease, Alzheimer s disease and ischemic stroke. The vast majority of PET studies reported to date have used 11C-(R,S) and 11C-(R)-PK 11195, a 3-isoquinolinecarboxamide antagonist, with nanomolar affinity for TSPO. Several second generation radioligands, including 11C-PBR28, 11C-DPA-713, and 11C-ER176 have been developed. Although these ligands have greater signal to noise (specific to nondisplaceable uptake) ratio than 11C-(R)-PK 11195,their binding to TSPO is affected by a single nucleotide polymorphism (SNP). Specific to nondisplaceable ratio of 11C-PBR28 has recently been reported. However, no one has ever measured the specific to nondisplaceable ratio of other TSPO radioligands including 11C-(R)-PK 11195, 11C-DPA-713 and 11C-ER176 in human subjects. In addition, differences in this binding site between species preclude comparisons based on studies in animals. The purposes of this study are to measure the signal to noise ratio (i.e., ratio of specific to non-displaceable uptake) of 11C-(R)-PK 11195, 11C-ER176 and 11C-DPA-713 in human subjects with two scans in each subject: at baseline and after emapunil, an agonist at the TSPO site and a putative anxiolytic based on studies in animals and in humans and study the effect of the SNP on the in vivo specific binding of the PET ligands.
Study population:
75 healthy volunteers in total aged 18 to 55 years. Of these, 25 will have 11C-(R)-PK 11195, 25 have 11C-DPA-713 scans, and 25 have 11C-ER176.
Design:
Healthy volunteers (n = up to 25) will have two scanning sessions using 11C-(R)-PK 11195: a) baseline i.e., medication-free and b) blocking i.e. with medication. For blocking, we will give one oral dose of emapunil (15 or 90 mg), about 1.5 hours before the second injection of the radioligand. Both scanning sessions would include an arterial line and measurement of the input function of parent radioligand separated from radiometabolites as well as plasma free fraction of radioligand. Additional 25 healthy volunteers will have two scanning sessions using 11C-DPA-713 in the same design, one baseline and another after one oral dose of emapunil. An additional 25 healthy volunteers will have two scanning sessions using 11C-ER176 in the same design, one baseline and another after one oral dose of emapunil. The total number of participants is 75 (= 25 + 25 + 25)
Outcome measures:
Baseline scans measure total binding i.e., total distribution volume (V[T]). By applying the Lassen plot, combined data from both baseline scans and those with administration of emapunil measure nonspecific binding i.e., nondisplaceable distribution volume (V[ND]). From these V[T] and V[ND] values, specific-to-nondisplaceable ratios will be calculated as (V[T] V[ND]) / V[ND[ and the influence of the SNP to specific binding, V[S] = V[T] - VND will also be studied.
- Conditions
- Baseline, Blocking Receptor Binding
- Being tested
- Emapunil, PET
- Keywords
- Health Humans, Receptor Occupancy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmapunilDrug
Single peroral administration
PETDevice
Positron emission tomography, which creates images by detecting radioactivity.
| Study group | Role | What they receive |
|---|---|---|
| Emapunil Administration | Experimental | Single Arm Study Receives: Drug: Emapunil; Device: PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Signal noise ratio [C-11](R)-PK 11195
Measured: 2 moths
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2014 (estimated)
- Study start24 Jun 2014
- Primary completion16 Jun 2016
- Study completion23 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BaselineStudies 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT02181582
- Sponsor's protocol ID
- 140141
- Other IDs
- 14-M-0141
- Status last verified
- 23 Nov 2016
- First submitted
- 2 Jul 2014
- Last updated
- 27 Sep 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Specific PET Radioligand Binding To Translocator Protein
- ClinicalTrials.gov ID
- NCT02181582
- Acronym / sponsor ID
- 140141
- Conditions
- Baseline, Blocking Receptor Binding
- Keywords
- Health Humans, Receptor Occupancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 24 Jun 2014
- Primary completion
- 16 Jun 2016 (actual)
- Study completion
- 23 Nov 2016 (actual)
- First posted
- 4 Jul 2014 (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:
- A brain protein called translocator protein (TSPO) shows changes in some brain diseases. A radioactive drug called 11C-(R)-PK 11195 is used to take pictures of TSPO using a camera called positron emission tomography (PET). Researchers want to find out how well 11C-(R)-PK 11195 takes the pictures.
Objective:
- To evaluate the radioactive chemical 11C-(R)-PK 11195.
Eligibility:
- Healthy volunteers ages 18-55.
Design:
- Participants will be screened with a medical exam.
- Participants will have scans at up to 4 visits.
- PET scan using 11C-(R)-PK 11195:
- A small tube (catheter) will be put into an artery at the wrist or elbow, by a needle. The needle will be removed, leaving only the catheter in the artery. Blood samples will be taken through this catheter.
- Another catheter will be placed into a vein in the arm or hand.
- 11C-(R)-PK 11195 will be injected through the second catheter.
- The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of it. They may get a plastic mask for their face and head.
- Participants will receive a dose of emapunil by mouth. Participants will then have another PET scan.
- Participants may have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that can slide in and out of the cylinder. Participants will get earplugs for the loud knocking noises.
- After each scan, participants will get a follow-up phone call. Two to seven days after taking emapunil, participants will return for a follow-up visit.
Detailed description
Objective:
The 18kDa Translocator Protein (TSPO, formerly known as the peripheral benzodiazepine receptor (PBR)) is expressed in activated microglia and reactive astrocyte. It has therefore been used as an imaging target for positron emission tomography (PET) to investigate diseases involving microglial activation and/or macrophage recruitment, such as multiple sclerosis, herpes encephalitis, Parkinson s disease, Alzheimer s disease and ischemic stroke. The vast majority of PET studies reported to date have used 11C-(R,S) and 11C-(R)-PK 11195, a 3-isoquinolinecarboxamide antagonist, with nanomolar affinity for TSPO. Several second generation radioligands, including 11C-PBR28, 11C-DPA-713, and 11C-ER176 have been developed. Although these ligands have greater signal to noise (specific to nondisplaceable uptake) ratio than 11C-(R)-PK 11195,their binding to TSPO is affected by a single nucleotide polymorphism (SNP). Specific to nondisplaceable ratio of 11C-PBR28 has recently been reported. However, no one has ever measured the specific to nondisplaceable ratio of other TSPO radioligands including 11C-(R)-PK 11195, 11C-DPA-713 and 11C-ER176 in human subjects. In addition, differences in this binding site between species preclude comparisons based on studies in animals. The purposes of this study are to measure the signal to noise ratio (i.e., ratio of specific to non-displaceable uptake) of 11C-(R)-PK 11195, 11C-ER176 and 11C-DPA-713 in human subjects with two scans in each subject: at baseline and after emapunil, an agonist at the TSPO site and a putative anxiolytic based on studies in animals and in humans and study the effect of the SNP on the in vivo specific binding of the PET ligands.
Study population:
75 healthy volunteers in total aged 18 to 55 years. Of these, 25 will have 11C-(R)-PK 11195, 25 have 11C-DPA-713 scans, and 25 have 11C-ER176.
Design:
Healthy volunteers (n = up to 25) will have two scanning sessions using 11C-(R)-PK 11195: a) baseline i.e., medication-free and b) blocking i.e. with medication. For blocking, we will give one oral dose of emapunil (15 or 90 mg), about 1.5 hours before the second injection of the radioligand. Both scanning sessions would include an arterial line and measurement of the input function of parent radioligand separated from radiometabolites as well as plasma free fraction of radioligand. Additional 25 healthy volunteers will have two scanning sessions using 11C-DPA-713 in the same design, one baseline and another after one oral dose of emapunil. An additional 25 healthy volunteers will have two scanning sessions using 11C-ER176 in the same design, one baseline and another after one oral dose of emapunil. The total number of participants is 75 (= 25 + 25 + 25)
Outcome measures:
Baseline scans measure total binding i.e., total distribution volume (V[T]). By applying the Lassen plot, combined data from both baseline scans and those with administration of emapunil measure nonspecific binding i.e., nondisplaceable distribution volume (V[ND]). From these V[T] and V[ND] values, specific-to-nondisplaceable ratios will be calculated as (V[T] V[ND]) / V[ND[ and the influence of the SNP to specific binding, V[S] = V[T] - VND will also be studied.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Emapunil Administration | Experimental | Drug: Emapunil, Device: PETSingle Arm Study |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
Key exclusion criteria (11 listed)
- Any past or present Axis I psychiatric disorder. Any history of alcohol or substance dependence, except nicotine dependence, within the past 6 months
- Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, or serious cardiopulmonary disease.
- Active seizure disorder, as defined as having had a seizure in the past year or being on antiepileptic medications for seizures.
- Positive HIV test.
- Recent research-related exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
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 |
|---|---|---|
| EmapunilSingle peroral administration | Drug | Emapunil Administration |
| PETPositron emission tomography, which creates images by detecting radioactivity. | Device | Emapunil Administration |
Primary outcome
Signal noise ratio [C-11](R)-PK 11195
Time frame: 2 moths
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 27 Sep 2018.
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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 Emapunil and PET in people with Baseline and Blocking Receptor Binding, 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 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 27 Sep 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.
What does the primary outcome measure?
Signal noise ratio [C-11](R)-PK 11195 (time frame: 2 moths). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Sep 2018.