30 Participants Needed

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

Recruiting at 1 trial location
RN
Overseen ByRajesh Narendran, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

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.

What data supports the idea that [C-11]NPA PET-Amphetamine for Cocaine Use Disorder is an effective treatment?

The available research shows that [C-11]NPA is a promising tool for imaging dopamine receptors in the brain, which are involved in addiction. However, the studies mainly focus on its ability to measure dopamine activity rather than directly treating cocaine use disorder. The research indicates that [C-11]NPA is more sensitive to changes in dopamine levels compared to other tracers, which could help in understanding how treatments affect the brain. But there is no direct evidence from these studies that it is an effective treatment for cocaine use disorder itself.12345

What safety data is available for the [C-11]NPA PET-Amphetamine treatment for cocaine use disorder?

The studies provided focus on the use of [11C]NPA as a radiotracer for imaging dopamine D2/3 receptors in the brain, both in nonhuman primates and humans. They evaluate the binding properties and competition with endogenous dopamine, particularly in response to amphetamine administration. However, these studies do not directly address safety data for the treatment of cocaine use disorder. They primarily assess the effectiveness and binding characteristics of the radiotracer in imaging studies. Therefore, specific safety data for the treatment itself is not detailed in the provided research.12356

Is the drug [C-11]NPA PET Scan a promising treatment for Cocaine Use Disorder?

[C-11]NPA PET Scan is a promising drug because it helps to image dopamine receptors in the brain, which are important for understanding and potentially treating conditions like Cocaine Use Disorder. It shows high sensitivity to changes in dopamine levels, making it a valuable tool for studying brain function and the effects of drugs like amphetamine.12345

What is the purpose of this trial?

This study uses \[11C\]NPA positron emission tomography (PET) and a d-amphetamine challenge to image amphetamine induced dopamine release in the striatum in subjects with cocaine use disorders (CUD). Amphetamine-induced dopamine release data from this study will be correlated with \[11C\]NOP-1A VT measured at baseline in the midbrain. \[11C\]NOP-1A PET data will be used from aim 1 (see, Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)

Research Team

RN

Rajesh Narendran

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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.
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Timeline

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

Treatment Details

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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: PETExperimental Treatment3 Interventions
\[C-11\]NPA PET Scan

Find a Clinic Near You

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+

Findings from Research

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.
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]
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.
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.
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]

References

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. [2021]
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. [2015]
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. [2021]
(-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors. [2019]
Quantitative analysis of (-)-N-(11)C-propyl-norapomorphine in vivo binding in nonhuman primates. [2016]
Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine. [2013]
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