Tau PET Imaging for Opioid Use Disorder
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Pennsylvania
Must be taking: Medication-assisted treatment
Disqualifiers: HIV, Epilepsy, Serious psychiatric disorder, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The investigators plan to enroll up to 60 adult subjects in this study. There will be three groups of up to 20 subjects each in this study.
Group 1: individuals with OUD and a history of at least one opioid-related OD in the past 5 years that required naloxone treatment reversal: OUD/OD+ Group 2: individuals with OUD without a lifetime history of opioid-related OD OUD/OD- Group 3: Healthy controls without a lifetime OUD: HCs 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.
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 data supports the effectiveness of the treatment 18F-PI-2620 PET/CT for opioid use disorder?
The research highlights the importance of PET imaging in understanding opioid receptors, which are crucial in substance dependence. 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, suggesting potential benefits in using similar imaging techniques for treatment evaluation.
12345How does this treatment differ from other treatments for opioid use disorder?
This treatment is unique because it uses tau PET imaging to study brain changes in opioid use disorder, focusing on the opioid receptor system, which is crucial in addiction. Unlike standard treatments that primarily target symptoms, this approach aims to understand the underlying brain mechanisms, potentially leading to more targeted therapies.
15678Eligibility Criteria
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.Inclusion Criteria
OUD OD- group: 18-60 years-old, Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures, Participants meet criteria for lifetime OUD and are currently in medication-assisted treatment for OUD with a stable dose of medication for at least 30 days prior to screening, No lifetime history of OD per self-report, Drug Overdose Questionnaire, and/or medical record review
OUD OD+ group: 18-60 years-old, Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures, Participants meet criteria for lifetime OUD and are currently in medication-assisted treatment for OUD with a stable dose of medication for at least 30 days prior to screening, A history of at least 1 opioid OD that required naloxone reversal up to 5 years prior to study enrollment per self-report, Drug Overdose Questionnaire, and/or medical record review
I am between 18-60, healthy, with no history of substance abuse except for cannabis, tobacco, or nicotine, and I haven't used opioids in the last 30 days.
Exclusion Criteria
My weight is over 350 pounds.
I have a history of epilepsy or seizures.
Contraindications to MRI
+10 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Tau PET/CTExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
Yale UniversityCollaborator
References
Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: an [11C]diprenorphine PET study. [2021]The importance of the opioid receptor system in substance dependence is increasingly recognised. We used PET with the non-selective tracer [11C]diprenorphine to examine opioid receptor binding in early abstinence from alcohol dependence and the relationship to craving. We recruited 11 alcohol dependent patients and 13 controls. Subjects underwent one [11C]diprenorphine PET scan in early abstinence from dependent alcohol use (approximately 2 weeks) and 2 months later if continuously abstinent. Global and regional [11C]diprenorphine volumes of distribution (VD) were increased in alcohol dependent patients compared with controls but did not reach significance. We demonstrated a correlation between global and regional [11C]diprenorphine VD and craving in alcohol dependent patients which persisted in the anterior cingulate cortex into extended abstinence. This confirms previous work showing increased opioid receptor availability in early abstinence from substances of abuse and correlation with craving suggesting that the opioid system plays a fundamental role in this phase of addiction.
Opioid Imaging. [2016]Many breakthrough scientific discoveries have been made using opioid imaging. Developments include the application of ever higher resolution whole-brain positron emission tomography (PET) scanners, the availability of several radioligands, the combination of PET with advanced structural imaging, advances in modeling macroparameters of PET ligand binding, and large-scale statistical analysis of imaging datasets. Suitable single-photon emission computed tomography (SPECT) tracers are lacking, but with the increase in the number of available PET (or PET/CT) cameras and cyclotrons thanks to the clinical successes of PET in oncology, PET may become widespread enough to overcome this. In the coming decade, there should be a more widespread application of the available techniques to patients and an impact in clinical medicine.
Classics in Neuroimaging: Shedding Light on Opioid Receptors with Positron Emission Tomography Imaging. [2021]Imaging of the opioid system was one of the earliest applications of Positron Emission Tomography (PET) imaging in neuroscience that remains in widespread use today and in the age of the opioid crisis the technique is as important as ever. In this viewpoint the rich history of opioid imaging using PET is highlighted, including discussion of the preferred radiotracers for imaging of μ, δ, κ and ORL-1 receptors in clinical applications. We also draw attention to key innovations that were essential to development of radiotracers for imaging opioid receptors including production of high molar activity PET radionuclides and new approaches to radiochemistry.
Synthesis and Evaluation of a 64Cu-Conjugate, a Selective δ-Opioid Receptor Positron Emission Tomography Imaging Agent. [2018]Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (DOP), this compound was selected for the design of a novel 64Cu-radiolabeled potent and selective DOP positron emission tomography (PET) imaging agent. Ex vivo autoradiography of TIPPD-PEG-K(NOTA/64Cu)-NH2 on rat brain sections produced a distribution pattern consistent with the known expression of DOP. Taken together, the in vitro and ex vivo data indicate that this 64Cu-tracer holds promise for studying the DOP by means of PET.
Regional cerebral metabolism alterations and functional connectivity in individuals with opioid use disorder: An integrated resting-state PET/fMRI study. [2023]Individuals with opioid use disorder (OUD) have been reported to show abnormal brain metabolism and impaired coupling among brain networks such as the default mode network (DMN), salience network (SN), and executive control network (ECN). However, the characteristics of brain glucose metabolism and its related functions in the brain networks in individuals with OUD remain unknown. Thirty-six individuals with OUD and thirty matched healthy controls (HCs) were recruited in this integrated positron emission tomography/magnetic resonance imaging (PET/MRI) study. Differences in glucose metabolism were analyzed by using 18F-fluorodeoxyglucose (18F-FDG), and the corresponding coupling characteristics of the individuals with OUD were also analyzed. The individuals with OUD showed widespread bilateral hypometabolism in the middle temporal gyrus (MTG), superior temporal gyrus, angular gyrus, supramarginal gyrus, inferior parietal lobe, Rolandic operculum, and left insula, but obvious hypermetabolism in the brainstem and left cerebellum. Meanwhile, in individuals with OUD, the hypometabolism of right MTG which is included in the DMN was accompanied by decreased coupling with the left superior frontal gyrus and right superior parietal gyrus which are included in the ECN. Furthermore, individuals with OUD showed a positive correlation between the duration of heroin use and glucose metabolism of the left MTG. The individuals with OUD were characterized by widespread bilateral hypometabolism in the temporal and parietal regions but obvious hypermetabolism in the brainstem and left cerebellum. The results suggest that the hypometabolism in the temporal and parietal regions might be related to DMN dysfunction and the hypermetabolism in the brainstem and left cerebellum may be compensate for other brain regions showing hypometabolism. In particular, hypometabolism in the self-referential-related DMN regions in OUD might attenuate their relationships with the inhibitory-control-related ECN regions. These findings highlight the importance of evaluating the metabolic and functional profiles of the right MTG in future studies on the treatment of OUD.
Imaging of opioid receptors in the central nervous system. [2021]In vivo functional imaging by means of positron emission tomography (PET) is the sole method for providing a quantitative measurement of mu-, kappa and delta-opioid receptor-mediated signalling in the central nervous system. During the last two decades, measurements of changes to the regional brain opioidergic neuronal activation--mediated by endogenously produced opioid peptides, or exogenously administered opioid drugs--have been conducted in numerous chronic pain conditions, in epilepsy, as well as by stimulant- and opioidergic drugs. Although several PET-tracers have been used clinically for depiction and quantification of the opioid receptors changes, the underlying mechanisms for regulation of changes to the availability of opioid receptors are still unclear. After a presentation of the general signalling mechanisms of the opioid receptor system relevant for PET, a critical survey of the pharmacological properties of some currently available PET-tracers is presented. Clinical studies performed with different PET ligands are also reviewed and the compound-dependent findings are summarized. An outlook is given concluding with the tailoring of tracer properties, in order to facilitate for a selective addressment of dynamic changes to the availability of a single subclass, in combination with an optimization of the quantification framework are essentials for further progress in the field of in vivo opioid receptor imaging.
Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals. [2023]Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.
Imaging opiate receptors in the human brain with positron emission tomography. Potential applications for drug addiction research. [2016]Positron emission tomography (PET) has been used mostly for the study of brain blood flow and metabolism in normal controls and in a variety of neurological and psychiatric conditions. With the appropriate radiotracers, PET also allows non-invasive imaging and quantification of a growing list of neuroreceptors. 11C-carfentanil and 11C-diprenorphine, 2 potent opiate ligands, have been used to label opiate receptors in vivo in man. Some advantages and limitations of this technique are discussed. PET is a unique tool that could help us understand, at the receptor level, some biochemical aspects of addiction to opiate drugs. Specific questions can be answered, but carefully designed protocols are required.