Tau PET Imaging for Opioid Use Disorder

Overseen By Hannah Straughn

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must be taking: Medication-assisted treatment

Disqualifiers: HIV, Epilepsy, Serious psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how tau, a protein in the brain, behaves in people with opioid use disorder (OUD) compared to healthy individuals. Participants will undergo a brain scan using a special radiotracer, 18F-PI-2620 PET/CT, to observe tau uptake in the brain. The trial includes three groups: those with OUD and a history of overdose, those with OUD but no overdose history, and healthy individuals without OUD. Individuals with a history of opioid overdose in the past five years or those with OUD currently receiving treatment may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding tau behavior in the brain, offering participants a chance to contribute to groundbreaking scientific knowledge.

Will I have to stop taking my current medications?

If you are in the OUD groups, you must be on a stable dose of your medication-assisted treatment for at least 30 days before the screening visit. The protocol does not specify if you need to stop other medications, so it's best to discuss this with the study team.

What prior data suggests that this PET/CT imaging is safe for humans?

Research has shown that 18F-PI-2620, the substance used in this trial, is generally safe in imaging studies. It is similar to Tauvid™, which the FDA has approved for imaging in other conditions, suggesting it is likely safe. Although specific safety information for 18F-PI-2620 in individuals with opioid use disorder is limited, its testing in an early-phase study indicates it has passed initial safety checks. The limited data available have reported no major side effects. Overall, 18F-PI-2620 appears to be a safe choice for PET/CT scans, but further research will help confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses a novel imaging method to better understand opioid use disorder (OUD) by focusing on tau protein buildup in the brain. Unlike traditional treatments that target withdrawal symptoms or opioid receptors, this approach uses the radiotracer 18F-PI-2620 in PET/CT scans to visualize tau deposits. This could provide new insights into the neurological changes associated with OUD, potentially leading to more effective treatments down the line. By identifying specific brain changes, this method could pave the way for personalized treatment plans and improve outcomes for individuals struggling with OUD.

What evidence suggests that this imaging technique is effective for evaluating tau uptake in opioid use disorder?

Research has shown that 18F-PI-2620 is a promising tool for imaging tau, a protein linked to changes in the brain. While there is no direct proof of its effectiveness for opioid use disorder, it has shown potential in improving brain imaging for conditions like Alzheimer's. Studies have demonstrated that this radiotracer helps detect tau build-up, providing insights into brain health. In this trial, participants will undergo a PET/CT scan using 18F-PI-2620 to evaluate tau uptake in the brain. This suggests that 18F-PI-2620 might help identify changes in the brain related to opioid use, although further research is needed to confirm this. Initial findings are encouraging for those studying brain changes associated with opioid disorders. ^{1 4 6 7 8}

Who Is on the Research Team?

Ilya Nasrallah, MD, PhD

Principal Investigator

Univeristy of Pennsylvania

Are You a Good Fit for This Trial?

Adults aged 18-60 with opioid use disorder (OUD) are eligible for this trial. It includes those who have had an overdose treated with naloxone in the past year, those without such a history, and healthy controls without OUD or recent opioid use. Participants must be on stable medication for OUD for at least 30 days and provide informed consent.

Exclusion Criteria

My weight is over 350 pounds.

I have a history of epilepsy or seizures.

Contraindications to MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Testing

Participants undergo PET/CT imaging to evaluate tau uptake and a comprehensive neurocognitive battery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and testing

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-PI-2620 PET/CT

Trial Overview The study is testing [18F]PI-2620 PET/CT imaging to measure tau protein uptake in the brain across three groups: individuals with OUD who've overdosed, those with OUD who haven't overdosed, and healthy controls.

How Is the Trial Designed?

Group I: Tau PET/CT Experimental Treatment 1 Intervention

PET/CT imaging will be used to evaluate the uptake of tau in the brain using the investigational radiotracer \[18F\]PI-2620. Each subject will have one \[18F\]PI-2620 positron emission tomography/computed tomography (PET/CT) scan performed. Participants will undergo approximately 30 minutes of static PET scanning of the brain and body starting approximately 45 minutes post injection of \[18F\]PI-2620. All images will be corrected for scatter and measured photon attenuation and reconstructed using standard reconstruction techniques. Standardized uptake value ratio (SUVr), the ratio of regional to reference uptake, will be calculated with cerebellum as reference, where NFTs are generally not present in neurodegenerative disorders, hence likely not in OUD. Subjects in all three groups undergo a brain MRI including a structural MRI functional reactivity to an episodic memory task, and undergo a comprehensive neurocognitive battery.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

Positron emission tomography (PET) is the only method that allows for quantitative measurement of opioid receptor signaling in the brain, which is crucial for understanding chronic pain and the effects of opioid drugs.

While various PET tracers have been used to study opioid receptors, the mechanisms regulating receptor availability remain unclear, highlighting the need for improved tracer properties and quantification methods to enhance the accuracy of in vivo imaging studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of opioid receptors in the central nervous system. Henriksen, G., Willoch, F.[2021]

Positron emission tomography (PET) is a powerful non-invasive imaging technique that can quantify neuroreceptors, including opiate receptors, using specific radiotracers like 11C-carfentanil and 11C-diprenorphine.

This imaging method can enhance our understanding of the biochemical mechanisms underlying opiate addiction, but it requires carefully designed research protocols to effectively address specific scientific questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging opiate receptors in the human brain with positron emission tomography. Potential applications for drug addiction research. Sadzot, B., Mayberg, HS., Frost, JJ.[2016]

Recent advancements in opioid imaging, particularly with high-resolution PET scanners and new radioligands, have significantly enhanced our ability to study the brain's opioid systems.

The increasing availability of PET technology, driven by its success in oncology, suggests that opioid imaging will become more common in clinical settings, potentially improving patient care in the next decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid Imaging. Hammers, A., Lingford-Hughes, A.[2016]

In a study involving 13 abstinent male alcohol dependents and 15 control participants, researchers found that alcohol dependence is associated with significantly reduced release of endogenous opioids in response to dexamphetamine, indicating a dysregulated opioid system.

Despite the reduced opioid release, there was no evidence of higher mu-opioid receptor availability in alcohol dependents compared to controls, suggesting that the blunted opioid response may contribute to addiction vulnerability and could inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals. Turton, S., Myers, JF., Mick, I., et al.[2023]

Individuals with opioid use disorder (OUD) exhibit widespread hypometabolism in key brain regions associated with cognitive functions, particularly in the temporal and parietal areas, which may indicate dysfunction in the default mode network (DMN).

There is a notable hypermetabolism in the brainstem and left cerebellum in individuals with OUD, suggesting a compensatory mechanism for the hypometabolic regions, and a correlation exists between the duration of heroin use and glucose metabolism in the left middle temporal gyrus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional cerebral metabolism alterations and functional connectivity in individuals with opioid use disorder: An integrated resting-state PET/fMRI study. Jin, L., Yuan, M., Zhang, W., et al.[2023]

In a study involving 11 alcohol-dependent patients and 13 controls, PET scans showed increased opioid receptor binding in alcohol-dependent individuals during early abstinence, indicating changes in the opioid system related to addiction.

The study found a correlation between opioid receptor availability and craving levels in alcohol-dependent patients, particularly in the anterior cingulate cortex, suggesting that the opioid system is crucial in the early stages of recovery from alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: an [11C]diprenorphine PET study. Williams, TM., Davies, SJ., Taylor, LG., et al.[2021]

The antagonist TIPP was successfully used to create a new 64Cu-radiolabeled PET imaging agent that selectively targets δ-opioid receptors (DOP), which could enhance our understanding of these receptors in the brain.

Ex vivo autoradiography showed that the distribution of the imaging agent in rat brain sections matched the known locations of DOP, indicating its potential effectiveness for studying DOP using PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Evaluation of a 64Cu-Conjugate, a Selective &#948;-Opioid Receptor Positron Emission Tomography Imaging Agent. Pirisedigh, A., Blais, V., Ait-Mohand, S., et al.[2018]

Positron Emission Tomography (PET) imaging has been crucial for studying the opioid system, especially during the ongoing opioid crisis, highlighting its importance in understanding opioid receptors.

The development of effective radiotracers for imaging different opioid receptors (μ, δ, κ, and ORL-1) has been driven by innovations in PET radionuclide production and advancements in radiochemistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classics in Neuroimaging: Shedding Light on Opioid Receptors with Positron Emission Tomography Imaging. Kaur, T., Wiesner, N., Kilbourn, MR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05651516

NCT05651516 | Tau PET Imaging in Opioid Use Disorder Effects of Opioid Use Disorder and Non-fatal Overdose on Tau Pathology; a [18F]PI-2620 PET/CT Study. Conditions. Opioid-Related Disorders. Opioid-Related ...

2. withpower.com withpower.com/trial/early-phase-1-opioid-related-disorders-11-2022-74b1f

Tau PET Imaging for Opioid Use Disorder Although not directly related to 18F-PI-2620, the studies show that PET imaging can provide valuable insights into brain changes in opioid use disorder, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35422444/

18F-PI-2620 Tau PET Improves the Imaging Diagnosis of ... These results provide evidence for an improved imaging-based PSP diagnosis by adding 18 F-PI-2620 tau PET to structural MRI.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39605030/

Head-to-head comparison of tau PET tracers [ 18 F]PI-2620 ... In this work, we aimed to compare the in-vivo uptake of tau tracers [18F]PI-2620 and [18F]RO948 in the early stages of the AD continuum. Methods ...

5. mdpi.com mdpi.com/1424-8247/14/2/110

Tauvid™: The First FDA-Approved PET Tracer for Imaging ... Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. J. Nucl. Med. 2020, 61, 911–919. [Google ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7911942/

Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau ... Tauvid has high selectivity towards tau over Aβ and is safe to be used in the clinical trials. Tauvid PET imaging can distinguish late-stage AD from cognitively ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9635682/

18F-PI-2620 Tau PET Improves the Imaging Diagnosis of ... The gain of sensitivity by adding 18F-PI-2620 PET to MRI data was more marked in clinically less affected patients than in more affected patients (37% vs. 19% ...

8. clinicaltrial.be clinicaltrial.be/en/details/174866?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Tau PET Imaging in Opioid Use Disorder PET/CT imaging will be used to evaluate the uptake of tau in the brain using the investigational radiotracer \[18F\]PI-2620. Each subject will ...