What is the mechanism of action of this treatment?

Common treatments targeting dopamine receptors include VMAT2 inhibitors like tetrabenazine and deutetrabenazine, which reduce dopamine release by inhibiting vesicular monoamine transporter 2, thereby alleviating symptoms of disorders like Huntington's disease. Antipsychotics, both typical and atypical, often act on D2/D3 receptors to manage psychotic symptoms by blocking dopamine activity. These treatments are crucial for patients with dopamine receptor-related conditions as they help modulate dopamine levels, thereby improving symptoms and quality of life. The study of radioligands like [18F]FTP for D3 receptor binding is important as it enhances our understanding of these mechanisms and aids in the development of more targeted therapies.

What side effects are associated with this type of intervention?

Common treatments targeting dopamine receptors, such as dopamine agonists and VMAT2 inhibitors, have a range of side effects. Dopamine agonists like sumanirole, which selectively targets D2 receptors, have an excellent safety profile but may be less effective than agents with combined D2/D3 activity. VMAT2 inhibitors like tetrabenazine can cause sedation, akathisia, parkinsonism, and depressed mood, which generally resolve with dose adjustments. Deutetrabenazine and valbenazine, also VMAT2 inhibitors, have a longer duration of action and improved side effect profiles compared to tetrabenazine.

What prior FDA approvals exist?

The FDA has approved several drugs targeting dopamine receptors, particularly for conditions like Huntington's disease and tardive dyskinesia. Tetrabenazine, deutetrabenazine, and valbenazine are VMAT2 inhibitors used for these conditions, with deutetrabenazine and valbenazine having a longer duration of action and improved side effect profiles compared to tetrabenazine. These drugs, while not specifically targeting D3 receptors, are relevant in the broader context of dopamine receptor modulation. The [18F]FTP trial aims to provide a more specific measure of D3 receptor binding, which could enhance understanding and treatment of various neuropsychiatric and movement disorders.

What other types of research exist?

A promising alternative to [18F]FTP for D3 receptor imaging is [18F]8b. This radioligand has demonstrated higher D3 receptor affinity, good in vivo stability, and specific accumulation in the striatum and cortex, making it a potential candidate for dopamine receptor imaging in 2024.

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[18F]FTP PET/CT Imaging for Cocaine Addiction

Phase 1 & 2

Waitlist Available

Led By Jacob Dubroff, MD PhD

Research Sponsored by University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants for Cohort 1 and 2 (Healthy Volunteers) must be 18-60 years of age

Participants for Cohort 3 and 4 (cocaine-dependent) must be males aged 18-60 years

Must not have

Females who are pregnant at the time of screening are not eligible for the study

Participants with contraindications to lorazepam are excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a special imaging substance to see how it attaches to certain brain receptors. It targets both healthy volunteers and people addicted to cocaine. The substance lights up specific brain areas when scanned, showing how well it sticks to these receptors. A specific compound has been shown to play a pivotal role in the reinforcing effects of cocaine.

Who is the study for?

This trial is for healthy males aged 18-60, or those with moderate to severe cocaine use disorder seeking treatment. Participants must be in good health as determined by an investigator and not have significant medical conditions that could affect the study or their safety. Pregnant women, individuals with certain medical conditions like liver disease, epilepsy, or severe respiratory issues are excluded.

What is being tested?

[18F]FTP PET/CT scans are being tested to measure D3 dopamine receptor binding in the brain. The study involves healthy volunteers and cocaine-dependent subjects who will receive either lorazepam or a placebo before scanning to assess [18F]FTP uptake variability.

What are the potential side effects?

Potential side effects may include reactions related to lorazepam such as drowsiness, sedation, unsteadiness, memory problems, and withdrawal symptoms after stopping the drug abruptly.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 60 years old.

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I am a male aged between 18 and 60 years and have a dependence on cocaine.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant.

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I cannot take lorazepam due to adverse reactions.

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I do not have serious gallbladder, kidney, or liver disease.

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I have never had epilepsy or seizures.

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I am not on any psychoactive medications.

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I have not used any dopamine-related stimulants in the last 30 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4: Cocaine-dependent Test/RetestExperimental Treatment1 Intervention

Up to 5 cocaine-dependent males who are voluntarily seeking treatment for cocaine dependence will participate in this imaging cohort. Each subject will undergo two dynamic \[18F\]FTP PET/CT brain scans on two separate days. This group will be used to test the variability of the \[18F\]FTP uptake measures in cocaine-dependent patients when scans are done following the consistent procedures with no other interventions. Subjects in all cohorts are required to have a structural brain MRI performed within 1 year of study enrollment. If the subject has not had a brain MRI that is deemed acceptable for use for this study, they will be asked to undergo a research brain MRI after they have consented for this study.

Group II: Cohort 3: Arterial samplingExperimental Treatment1 Intervention

Up to 5 cocaine-dependent males who are voluntarily seeking treatment for cocaine dependence will participate in this imaging cohort. Each subject will undergo one dynamic \[18F\]FTP PET/CT brain scan. Patients will have an arterial line placed for blood draws during the scan. This group will be used to determine the arterial blood input and FTP parent to metabolite ratio curves for FTP for a cocaine-dependent patient population for comparison with previously collected data in healthy normal volunteers. Subjects in all cohorts are required to have a structural brain MRI performed within 1 year of study enrollment. If the subject has not had a brain MRI that is deemed acceptable for use for this study, they will be asked to undergo a research brain MRI after they have consented for this study.

Group III: Cohort 2: Healthy Volunteer Test/RetestExperimental Treatment1 Intervention

Up to 10 healthy volunteers will participate in a serial imaging cohort. Each subject will undergo two dynamic \[18F\]FTP PET/CT brain scans on two separate days. Subjects in all cohorts are required to have a structural brain MRI performed within 1 year of study enrollment. If the subject has not had a brain MRI that is deemed acceptable for use for this study, they will be asked to undergo a research brain MRI after they have consented for this study.

Group IV: Cohort 1a: Lorazepam; 1b: PerphenazineExperimental Treatment1 Intervention

Up to 5 healthy volunteers will participate in a double-blind, placebo controlled serial imaging cohort 1a. Each subject will undergo two dynamic \[18F\]FTP PET/CT brain scans on two separate days. On one scan day the patient will receive an IV injection of normal saline (placebo) prior to the FTP brain scan, on the other scan day the patient will receive an IV injection of lorazepam prior to the planned FTP injection scan. The type of injection (placebo versus lorazepam) will be double-blinded to the patient and the injecting nuclear medicine Authorized User. Up to 5 subjects will participate in Cohort 1b where subjects will undergo two FTP PET/CT with and without perphenazine. Subjects in all cohorts are required to have a structural brain MRI performed within 1 year of study enrollment. If the subject has not had a brain MRI that is deemed acceptable for use for this study, they will be asked to undergo a research brain MRI after they have consented for this study.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments targeting dopamine receptors include VMAT2 inhibitors like tetrabenazine and deutetrabenazine, which reduce dopamine release by inhibiting vesicular monoamine transporter 2, thereby alleviating symptoms of disorders like Huntington's disease. Antipsychotics, both typical and atypical, often act on D2/D3 receptors to manage psychotic symptoms by blocking dopamine activity. These treatments are crucial for patients with dopamine receptor-related conditions as they help modulate dopamine levels, thereby improving symptoms and quality of life. The study of radioligands like [18F]FTP for D3 receptor binding is important as it enhances our understanding of these mechanisms and aids in the development of more targeted therapies.

Maternal dopamine encodes affective signals of human infants.Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.The utility of (11)C-arachidonate PET to study in vivo dopaminergic neurotransmission in humans.