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Alzheimer DiseasePhase 1/2NCT05374278

First-in-Human Evaluation of an Astrocytic Glutamate Transporter (EAAT2) PET Tracer in Dementia

A Phase 1/2 study testing [18F]RP-115 PET/MRI or PET/CT and MRI in people with Alzheimer Disease and Frontotemporal Dementia, run by David Wilson at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a first in human study that will assess the safety and diagnostic performance of [18F]RP-115 (fluorine-18 labeled RP115), a positron emission tomography (PET) agent. This agent has the potential to identify the early changes that occur in the brains of patients with Alzheimer's disease (AD) and frontotemporal… Read more about this study

Who is it for?
Ages 40 to 75 yearsHealthy volunteers can take part
What is being tested?
[18F]RP-115 PET/MRI or PET/CT and MRI
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
1 siteUnited States
Study dates
2 Nov 2021to 31 May 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 40 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age 40-75
  • Age-suitable BMI
  • Ability to provide written informed consent and willingly comply with protocol requirements or has a legal authorized representative/guardian who provides surrogate informed consent.
  • No apparent physical disorder.
  • Radial, ulnar, or brachial artery suitable for catheterization.
  • Non-smoker, and not taking OTC nicotine cessation - to limit peripheral metabolism events.
Show all 10Show fewer
  • Devoid of CNS prescription drugs for three weeks - to limit peripheral metabolism events.
  • For Cohort 2B and 2C:
  • Must have a study partner (informant) who spends a minimum average of 5 hours per week with the participant (e.g. family member, significant other, friend, caregiver), is generally aware of the participant's daily activities, can provide information about the participant's cognitive and functional performance, and will accompany the participant in all study procedure.
  • Recent (within 6 mo.) MME clinical scores.

Who cannot join

  • Unable to provide written informed consent and unwilling to comply with protocol requirements, or does not have a legal authorized representative/guardian who can provide surrogate informed consent.
  • Inadequate arterial access.
  • Receipt of radioisotope < 5 half-lives within [18F]RP-115 imaging- as to not confound any scans with radiation background for previous scanning, and unsuitable organ dosimetry thresholds from previous (> two weeks) PET scans.
  • The performed [18F]RP-115 scan(s) must not represent > 3 PET studies total within one year.
  • Contra-indication to magnetic resonance, including permanent pacemaker, implantable metallic device, etc.; or severe claustrophobia.
  • Participants who are pregnant (female patients of childbearing age will be tested prior to injection of tracer- positive test excludes from the study)
  • Participants who are breast-feeding.
  • Have a medical condition or other circumstances that in the opinion of the project physicians would significantly decrease chances of obtaining reliable data, achieving the study objective or completing the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

David Wilson, MD, PhD contact

415-514-6229

david.m.wilson@ucsf.edu

Henry Vanbrocklin, PhD contact

415-353-4569

henry.vanbrocklin@ucsf.edu

United States1 site, 1 recruiting

  • China Basin, UCSF

    San Francisco, California, 94107

    David Wilson, MD, PhD, david.m.wilson@ucsf.edu

    Recruiting

Other trials in United States

About this study

Official title: First-in-Human Evaluation of an Astrocytic Glutamate Transporter (EAAT2) PET Tracer in the Brains of Healthy Controls and Patients With Dementia.

This is a first in human study that will assess the safety and diagnostic performance of [18F]RP-115 (fluorine-18 labeled RP115), a positron emission tomography (PET) agent. This agent has the potential to identify the early changes that occur in the brains of patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD).

Read the detailed description

AD and FTD are the two leading causes of dementia with tremendous impact on patients and their families. Early diagnosis of both AD and FTD is essential to increase patients' quality of life, identify and treat reversible causes, and enhance the development and effectiveness of treatments. However, no single diagnostic agent is currently available for either AD or FTD; instead, clinicians must rely on the patient's history and cognitive testing which often leads to delayed or incorrect diagnosis. Importantly AD and FTD have distinct regional patterns of neuronal loss and dysfunction in the brain; an agent that could detect these regionally specific changes early in the course of the disease process could revolutionize diagnosis and treatment development for these conditions.

This study aims to develop a novel radiotracer to fill this unmet need. The excitatory amino acid transporter 2 (EAAT2) is the main transporter for glutamate in the brain and has been shown to be downregulated in the context of AD and other neurodegenerative conditions. EAAT2 is responsible for over 90% of glutamate uptake in the brain where it is primarily located on astrocytes and plays a key role in maintaining the homeostasis of the tripartite synapse. The goal of this study is to test the EAAT2 targeted positron emitting agent, [18F]RP-115, to evaluate early changes in astrocytes in healthy controls versus patients with AD and FTD by quantitative PET imaging of EAAT2. We have preclinical data that demonstrates that this agent is a good predictor of EAAT2 levels in animal models, hence, can potentially detect early signs of neurodegeneration. We now wish to test this agent in humans.

In summary, the primary objective of this study is to demonstrate human safety and measure the biodistribution of [18F]RP-115 in healthy controls as well as in age-matched patients with AD and FTD.

Being tested
[18F]RP-115 PET/MRI or PET/CT and MRI
Keywords
Alzheimer Disease, Nuclear medicine, Positron emission tomography, Magnetic resonance imaging, Frontotemporal Dementia
Medical subject headings
Alzheimer Disease, Frontotemporal Dementia, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [18F]RP-115 PET/MRI or PET/CT and MRIDrug

    An I.V. bolus injection of up to 10 millicurie (mCi) [18F]RP-115 will be administered, followed by a PET/MRI scan or by a combination of PET/CT and MRI

Study groups in NCT05374278
Study groupRoleWhat they receive
Cohort 1 - dosimetry of [18F]RP-115 in healthy volunteersExperimentalEstablish [18F]RP-115 safety in the clinic with male and female PET imaging.
Receives: Drug: [18F]RP-115 PET/MRI or PET/CT and MRI
Cohort 2B - [18F]RP-115 in patients with ADExperimentalComparison of [18F]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Receives: Drug: [18F]RP-115 PET/MRI or PET/CT and MRI
Cohort 2C - [18F]RP-115 in patients with FTDExperimentalComparison of [18F]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Receives: Drug: [18F]RP-115 PET/MRI or PET/CT and MRI
Cohort 2A - [18F]RP-115 in age-matched controlsExperimentalComparison of [18F]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Receives: Drug: [18F]RP-115 PET/MRI or PET/CT and MRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of Administered dose

    Each study participant will undergo a physical examination, vital signs, and ECGs prior to and after the scan and will also be monitored during the scan for adverse events. Additionally, a follow-up with the subject will be conducted 24-48 hours after [18F]RP-115 administration.

    Outcome Measure: Any adverse events will be recorded and graded according to Common Terminology Criteria for Adverse Events.

    Measured: A year

  2. Dosimetry of [18F]RP-115

    Whole-body PET/MRI scan will be conducted immediately after an [18F]RP-115 injection and last about 3.5 hours (including breaks) in 8 healthy volunteers (male and female). Equivalent organ radiation doses will be calculated in selected organs using the dynamic PET/MRI data in order to calculate the dosimetry of the tracer.

    Outcome Measure: Radiation exposure per organ as milliSievert/kg

    Measured: A year

  3. Biodistribution of [18F]RP-115

    Whole-body PET/MRI scan will be conducted immediately after an [18F]RP-115 injection and last about 3.5 hours (including breaks) in 8 healthy volunteers (male and female). Percent injected activity (%IA) will be calculated in selected organs using the dynamic PET/MRI data in order to calculate the biodistribution of the tracer.

    Outcome Measure: Percent injected activity (%Injected radioactivity) in selected organs.

    Measured: A year

Secondary outcomes (1)

  1. [18F]RP-115 diagnostic performance

    Utilize RP-115 to quantitatively assess regional cerebral RP-115 binding differences in healthy volunteers compared to cognitively-defined AD and FTD.

    Outcome Measure: Radioactivity distribution volume across cerebral cortex, Becquerel/mL or standardized uptake value.

    Measured: Three years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2022
  2. Study start2 Nov 2021
  3. Primary completion3 Apr 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

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 1/2
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
102 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05374278
Sponsor's protocol ID
13180640
Status last verified
Apr 2025
First submitted
24 Dec 2021
Last updated
17 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All of the individuals participants data collected during the trial, after de-identification.

Publications

  • Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.

    PubMed 29653606

  • Boche D, Gerhard A, Rodriguez-Vieitez E; MINC Faculty. Prospects and challenges of imaging neuroinflammation beyond TSPO in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2019 Dec;46(13):2831-2847. doi: 10.1007/s00259-019-04462-w. Epub 2019 Aug 8.

    PubMed 31396666

  • Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9. doi: 10.1038/sj.jcbfm.9600493. Epub 2007 May 9.

    PubMed 17519979

  • Rice L, Bisdas S. The diagnostic value of FDG and amyloid PET in Alzheimer's disease-A systematic review. Eur J Radiol. 2017 Sep;94:16-24. doi: 10.1016/j.ejrad.2017.07.014. Epub 2017 Jul 20.

    PubMed 28941755

  • Rodriguez-Vieitez E, Carter SF, Chiotis K, Saint-Aubert L, Leuzy A, Scholl M, Almkvist O, Wall A, Langstrom B, Nordberg A. Comparison of Early-Phase 11C-Deuterium-l-Deprenyl and 11C-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease. J Nucl Med. 2016 Jul;57(7):1071-7. doi: 10.2967/jnumed.115.168732. Epub 2016 Feb 16.

    PubMed 26912447

  • Arakawa R, Stenkrona P, Takano A, Nag S, Maior RS, Halldin C. Test-retest reproducibility of [11C]-L-deprenyl-D2 binding to MAO-B in the human brain. EJNMMI Res. 2017 Dec;7(1):54. doi: 10.1186/s13550-017-0301-4. Epub 2017 Jun 20.

    PubMed 28634836

  • Cowburn R, Hardy J, Roberts P, Briggs R. Presynaptic and postsynaptic glutamatergic function in Alzheimer's disease. Neurosci Lett. 1988 Mar 21;86(1):109-13. doi: 10.1016/0304-3940(88)90192-9.

    PubMed 2896322

  • Scott HL, Tannenberg AE, Dodd PR. Variant forms of neuronal glutamate transporter sites in Alzheimer's disease cerebral cortex. J Neurochem. 1995 May;64(5):2193-202. doi: 10.1046/j.1471-4159.1995.64052193.x.

    PubMed 7722505

  • Hoshi A, Tsunoda A, Yamamoto T, Tada M, Kakita A, Ugawa Y. Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease. Neuropathol Appl Neurobiol. 2018 Oct;44(6):628-638. doi: 10.1111/nan.12475. Epub 2018 Mar 4.

    PubMed 29405337

  • Li S, Mallory M, Alford M, Tanaka S, Masliah E. Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J Neuropathol Exp Neurol. 1997 Aug;56(8):901-11. doi: 10.1097/00005072-199708000-00008.

    PubMed 9258260

  • Pasqualetti G, Brooks DJ, Edison P. The role of neuroinflammation in dementias. Curr Neurol Neurosci Rep. 2015 Apr;15(4):17. doi: 10.1007/s11910-015-0531-7.

    PubMed 25716012

  • Miller ZA, Sturm VE, Camsari GB, Karydas A, Yokoyama JS, Grinberg LT, Boxer AL, Rosen HJ, Rankin KP, Gorno-Tempini ML, Coppola G, Geschwind DH, Rademakers R, Seeley WW, Graff-Radford NR, Miller BL. Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts: Completing the picture. Neurol Neuroimmunol Neuroinflamm. 2016 Oct 28;3(6):e301. doi: 10.1212/NXI.0000000000000301. eCollection 2016 Dec.

    PubMed 27844039

  • Arnold SE, Han LY, Clark CM, Grossman M, Trojanowski JQ. Quantitative neurohistological features of frontotemporal degeneration. Neurobiol Aging. 2000 Nov-Dec;21(6):913-9. doi: 10.1016/s0197-4580(00)00173-1.

    PubMed 11124442

  • Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang HY, Shang Y, Oldham MC, Martens LH, Gao F, Coppola G, Sloan SA, Hsieh CL, Kim CC, Bigio EH, Weintraub S, Mesulam MM, Rademakers R, Mackenzie IR, Seeley WW, Karydas A, Miller BL, Borroni B, Ghidoni R, Farese RV Jr, Paz JT, Barres BA, Huang EJ. Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Cell. 2016 May 5;165(4):921-35. doi: 10.1016/j.cell.2016.04.001. Epub 2016 Apr 21.

    PubMed 27114033

  • Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, Ma X, Ma Y, Iadecola C, Beal MF, Nathan C, Ding A. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med. 2010 Jan 18;207(1):117-28. doi: 10.1084/jem.20091568. Epub 2009 Dec 21.

    PubMed 20026663

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing [18F]RP-115 PET/MRI or PET/CT and MRI in people with Alzheimer Disease and Frontotemporal Dementia, run by David Wilson 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 10 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: looking for participants now, as of the sponsor's last update on 17 Apr 2025. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Wilson, MD, PhD (415-514-6229, david.m.wilson@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Administered dose (time frame: A year). The study lists 3 primary outcomes in all. 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 NCT05374278, which also lists 15 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 Apr 2025.

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