[C-11]NPA PET-Amphetamine for Cocaine Use Disorder

Recruiting at 1 trial location

Overseen By Rajesh Narendran, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rajesh Narendran

Must not be taking: Prescription medications

Disqualifiers: Psychiatric disorders, Opiate abuse, others

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

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand dopamine release, a feel-good chemical, in individuals with cocaine use disorder. Researchers will use a PET scan to observe the brain's reaction to amphetamines, a type of stimulant, and aim to link these reactions to other brain activity patterns. Individuals diagnosed with cocaine use disorder, without other major mental health or addiction issues, might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking scientific knowledge.

Do I have to stop taking my current medications for the trial?

Yes, you must not be on any prescription medical or psychotropic medications to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the [C-11]NPA PET scan examines dopamine receptors in the brain, aiding in the understanding of brain chemistry. However, specific safety information for its use in individuals with cocaine use disorder remains limited, so exact safety details are not fully known.

For the d-amphetamine part of the trial, more information is available. D-amphetamine, a stimulant affecting the brain, is often used in medications for conditions like ADHD. While the FDA has approved it for certain uses, it can cause side effects, such as a faster heartbeat and potential misuse.

As this trial is in an early stage, it focuses on understanding how these treatments work in the body. Safety details are still under study. Participants should be aware of this and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for cocaine use disorder, like behavioral therapy or medications aimed at reducing cravings, focus on managing symptoms and behavior. But this new approach uses a [C-11]NPA PET scan technique to offer a different angle. Researchers are excited because it allows them to visualize and measure dopamine receptor activity in the brain before and after amphetamine exposure. This could provide deeper insights into how cocaine affects the brain and pave the way for more targeted treatments in the future. By understanding the precise brain changes involved, it could lead to breakthroughs that current treatments don't address.

What evidence suggests that this trial's treatments could be effective for cocaine use disorder?

Research has shown that d-amphetamine, a type of stimulant, can help reduce cocaine use. Studies have found that people taking d-amphetamine experienced fewer cravings and used less cocaine. One study demonstrated that rats given d-amphetamine were less likely to take cocaine on their own, suggesting it might help reduce addictive behaviors. Another study found that people using d-amphetamine showed a decrease in cocaine use. In this trial, participants will undergo a [C-11]NPA PET scan to assess the effects of d-amphetamine on cocaine use disorder. Overall, these findings suggest that d-amphetamine might effectively treat cocaine use disorder by reducing both cravings and usage. ^{6 7 8 9 10}

Who Is on the Research Team?

Rajesh Narendran

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-55 with a diagnosis of cocaine use disorder. Participants must not be on medications, have high blood pressure or heart rate, or be pregnant/breastfeeding. They should not have major psychiatric disorders, severe medical conditions, or a family history of early heart attacks/strokes/psychosis. No heavy recent use of other drugs/alcohol and must have completed a related PET scan in another study.

Inclusion Criteria

No baseline BP ≥ 140/90 and/or HR ≥ 100

None of my immediate family had a heart attack or stroke before middle age.

I have completed a specific PET scan for a previous study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline PET Scan

Participants undergo a baseline PET scan to measure initial NOP receptor binding

1 day

1 visit (in-person)

Amphetamine Challenge and PET Scan

Participants receive d-amphetamine and undergo a PET scan to measure dopamine release

1 day

1 visit (in-person)

Follow-up

Participants are monitored for relapse and other outcomes over a 12-week period

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baseline [C-11]NPA PET Scan
• d-amphetamine
• Post-amphetamine [C-11]NPA PET Scan

Trial Overview The study tests how d-amphetamine affects dopamine release in the brain using [C-11]NPA PET scans before and after administering d-amphetamine to individuals with cocaine use disorders. It aims to link these effects to previous midbrain imaging results from an earlier phase of the research.

How Is the Trial Designed?

Group I: PET Experimental Treatment 3 Interventions

\[C-11\]NPA PET Scan

Who Is Running the Clinical Trial?

Rajesh Narendran

Lead Sponsor

Trials

4

Recruited

180+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The novel PET tracer 2-Cl-[(11)C]-(-)-NPA was developed with high selectivity for dopamine D(2) receptors over D(3) receptors, but it showed slower brain uptake compared to the existing tracer [(11)C]-(-)-NPA.

Despite its selectivity, 2-Cl-[(11)C]-(-)-NPA demonstrated inferior performance as a PET tracer in rats due to lower specific binding and slower accumulation in the striatum, indicating it may not be as effective for imaging dopamine release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine. Palner, M., McCormick, P., Gillings, N., et al.[2013]

The study evaluated the new PET radiotracer (-)-N-(11)C-propyl-norapomorphine ((11)C-NPA) in two baboons, demonstrating its potential to effectively image high-affinity states of dopamine D(2)-like receptors in the brain.

Using a 1-tissue compartment model, the study found that (11)C-NPA provided reliable estimates of striatal binding potential and tissue distribution volumes, confirming its suitability for quantifying receptor activity in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative analysis of (-)-N-(11)C-propyl-norapomorphine in vivo binding in nonhuman primates. Hwang, DR., Narendran, R., Huang, Y., et al.[2016]

In a study using PET imaging in three male baboons, the radiotracer [11C]NPA showed greater sensitivity to fluctuations in synaptic dopamine levels compared to the reference antagonist [11C]raclopride, indicating that [11C]NPA may be more effective for assessing D2 receptor activity in vivo.

The results suggest that a significant majority (71%) of D2 receptors are in a high-affinity state for agonists, highlighting the potential of [11C]NPA as a superior tool for investigating presynaptic dopamine function in both healthy and diseased states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propyl-norapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride. Narendran, R., Hwang, DR., Slifstein, M., et al.[2015]

The study found that the radiotracer [(11)C]NPA, which targets dopamine D(2/3) receptors, is more susceptible to competition from endogenous dopamine than the reference antagonist radiotracer [(11)C]raclopride, indicating a higher vulnerability in imaging D(2/3) receptors under conditions of increased synaptic dopamine.

In a PET study involving 10 healthy subjects, both [(11)C]NPA and [(11)C]raclopride showed significant reductions in binding potential after administration of d-amphetamine, with [(11)C]NPA showing a greater percentage decrease, suggesting that agonist radiotracers like [(11)C]NPA may be less reliable for imaging in dynamic dopamine environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative evaluation of the dopamine D(2/3) agonist radiotracer [11C](-)-N-propyl-norapomorphine and antagonist [11C]raclopride to measure amphetamine-induced dopamine release in the human striatum. Narendran, R., Mason, NS., Laymon, CM., et al.[2021]

The study demonstrated that the radiotracer [(11)C]NPA can reliably measure dopamine D(2/3) receptors in the human brain, showing excellent reproducibility in binding parameters across different regions of the striatum.

Using a two-tissue compartment kinetic model provided accurate estimates of receptor binding, with high intraclass correlation coefficients, indicating that [(11)C]NPA is a valuable tool for imaging D(2/3) receptors in a high-affinity state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography imaging of D(2/3) agonist binding in healthy human subjects with the radiotracer [(11)C]-N-propyl-norapomorphine: preliminary evaluation and reproducibility studies. Narendran, R., Frankle, WG., Mason, NS., et al.[2021]

The new radiolabeled D(2) agonist, (-)-[(11)C]NPA, shows high uptake in D(2) receptor-rich areas in both rodents and baboons, indicating its potential as an effective PET tracer for studying D(2) receptors in vivo.

The study demonstrated that pretreatment with haloperidol significantly reduced the striatum/cerebellum ratio of (-)-[(11)C]NPA, confirming its specific binding to D(2) receptors and suggesting its utility in assessing receptor affinity states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors. Hwang, DR., Kegeles, LS., Laruelle, M.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3417072/

Psychostimulant Treatment of Cocaine Dependence - PMC Dextroamphetamine has been shown to produce dose-dependent reductions in cocaine self-administration in rats.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833773

Safety of Stimulants Across Patient Populations: A Meta- ... This meta-analysis found an increased risk of AEs with stimulant use compared with placebo, without clinically significant cardiovascular ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871624002497

Treatment with dextroamphetamine decreases the ... These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4456227/

Extended-Release Mixed Amphetamine Salts vs Placebo ... In this trial, extended-release mixed amphetamine salts administered at robust doses along with CBT improved outcome in both ADHD symptoms and cocaine ...

5. substanceabusepolicy.biomedcentral.com substanceabusepolicy.biomedcentral.com/articles/10.1186/s13011-021-00399-2

a qualitative study with patients receiving injectable opioid ... A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine.

6. withpower.com withpower.com/trial/early-phase-1-disease-8-2021-ce3da

[C-11]NPA PET-Amphetamine for Cocaine Use Disorder However, these studies do not directly address safety data for the treatment of cocaine use disorder. They primarily assess the effectiveness and binding ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2749304/

PET Imaging of D2/3 agonist binding in healthy human ... N-[11C]-Propyl-norapomorphine (NPA) is a full dopamine D2/3 receptor agonist radiotracer suitable for imaging D2/3 receptors configured in a state of high ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3148950/

Current perspectives on selective dopamine D3 receptor ... ... 11C]NPA((–)-N-[11C]propyl-norapomorphine)) that show preferential uptake in the dorsal striatum. Furthermore, the specific binding of [11C](+)-PHNO in ...

9. nature.com nature.com/articles/1301400

First Human Evidence of d-Amphetamine Induced ... In a PET study performed in cats, Ginovart et al (2006a) have shown not only that [11C]-(+)-PHNO is more vulnerable towards d-amphetamine ...

10. datasheets.scbt.com datasheets.scbt.com/sc-80681.pdf

sc-80681 - Amphetamine (AMP2) Amphetamine-induced dopamine release: Duration of action as assessed with the D2/3 receptor agonist radiotracer (--)-N-[11C]propyl-norapomorphine ([11C]NPA) in ...