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(1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE

This article discusses clinical trials investigating (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE, a radiotracer used in PET imaging. The trials aim to evaluate changes in the brain’s serotonin system during the early stages of Parkinson’s disease. Researchers are studying people who carry specific genetic mutations that increase their risk of developing Parkinson’s disease.

Table of Contents

Overview of the Clinical Trial

A Phase 4 clinical trial is currently investigating the use of (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE, also known as [11C]SB207145, in studying the early stages of Parkinson’s disease[1]. The trial, designated as 2024-516610-38-00 and titled “Assessment of the impairment of the serotoninergic system during the prodromal phase of Parkinson’s disease in SNCA mutation carriers by PET using [11C]DASB and [11C]SB207145: SerIAL-PD,” has been authorized and is designed as an interventional study[1].

The research focuses on understanding how the serotoninergic system in the brain becomes impaired during the prodromal phase of Parkinson’s disease, which is the period before obvious motor symptoms appear[1]. This early detection research is particularly important because it may help identify disease processes before significant damage has occurred in the brain.

Understanding the Radiotracer

(1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE is a specialized radioactive compound used in positron emission tomography (PET) imaging[1]. This substance is specifically designed to bind to 5-HT4 receptors, which are a type of serotonin receptor found in the brain.

The radiotracer works by temporarily attaching to these receptors, allowing researchers to visualize and measure their distribution and density in different brain regions using PET scanning technology[1]. This imaging technique provides valuable information about the functioning of the serotonin system without requiring invasive procedures.

In this trial, (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE is being used alongside another radiotracer called [11C]DASB, which binds to the serotonin transporter (SERT)[1]. Together, these two radiotracers provide a comprehensive picture of different components of the serotonin system in the brain.

Study Population and Enrollment

The clinical trial plans to enroll approximately 50 participants divided into two distinct groups[1]. The study population has been carefully selected to investigate specific aspects of Parkinson’s disease development in at-risk individuals.

SNCA Mutation Carriers Without Parkinson’s Disease (SNCA+ PD-)

The first group consists of individuals who carry mutations in the SNCA gene, also known as the alpha-synuclein gene, but who do not yet have a diagnosis of Parkinson’s disease[1]. These participants are considered to be at higher risk for developing Parkinson’s disease due to their genetic profile. The SNCA gene provides instructions for making a protein called alpha-synuclein, and mutations in this gene are known to be associated with both familial and sporadic forms of Parkinson’s disease.

By studying these individuals before they develop symptoms, researchers can gain insights into the earliest brain changes that occur in Parkinson’s disease[1]. This approach allows for the investigation of the prodromal phase, when disease processes may be beginning but have not yet caused noticeable symptoms.

Healthy Control Participants (SNCA- PD-)

The second group serves as a control group and includes healthy individuals who do not carry SNCA gene mutations and do not have Parkinson’s disease[1]. This comparison group is essential for determining what differences in serotonin system function are specifically related to the genetic risk for Parkinson’s disease versus normal variation in the population.

Trial Methodology and Interventions

The trial employs a specific protocol for administering the radiotracers and conducting imaging studies[1]. Understanding the methodology helps clarify what participants can expect during the study.

Administration of (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE

The radiotracer (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE is administered at a concentration of 74 MBq/ml (megabecquerels per milliliter) via intravenous bolus injection or IV infusion[1]. This means the substance is delivered directly into a vein, allowing it to quickly circulate through the bloodstream and reach the brain.

The radioactive component of the tracer has a relatively short half-life, which means it decays quickly and does not remain in the body for extended periods[1]. This characteristic makes it safe for use in imaging studies while still providing sufficient time to capture detailed brain images.

Administration of [11C]DASB

In addition to (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE, participants also receive [11C]DASB at a dose of 4 MBq/kg (megabecquerels per kilogram of body weight)[1]. This second radiotracer is administered through the same method of intravenous bolus injection or IV infusion.

The use of two different radiotracers allows researchers to examine multiple aspects of the serotonin system in the same individuals[1]. While (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE targets the 5-HT4 receptor, [11C]DASB binds to the serotonin transporter, providing complementary information about serotonin system function.

Primary Objectives and Outcomes

The primary objective of this clinical trial is to determine and compare the PET-binding potential of the radiotracer ligands [11C]DASB and [11C]SB207145 (which is another name for (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE) to their respective targets[1].

Measuring Binding Potential

The binding potential is a quantitative measure that reflects the density and availability of specific molecular targets in the brain[1]. For (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE, this means measuring how much of the radiotracer binds to 5-HT4 receptors in different brain regions. A higher binding potential generally indicates more receptors are available, while a lower binding potential may suggest receptor loss or dysfunction.

Similarly, the binding potential of [11C]DASB to the serotonin transporter (SERT) provides information about the integrity of serotonin-producing neurons and their ability to regulate serotonin levels in the brain[1].

Comparison Between Groups

The key comparison in this study is between SNCA mutation carriers without Parkinson’s disease (SNCA+ PD-) and healthy controls without the mutation (SNCA- PD-)[1]. By analyzing differences in binding potential between these groups, researchers aim to identify alterations in the serotonin system that occur in individuals at genetic risk for Parkinson’s disease, even before clinical symptoms appear.

This comparison may reveal whether changes in 5-HT4 receptors or serotonin transporters represent early biomarkers of Parkinson’s disease development[1]. Such biomarkers could potentially be used in the future to identify individuals who might benefit from early intervention or monitoring.

Clinical Significance

The investigation of (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE in this clinical trial represents an important step in understanding the early pathological changes in Parkinson’s disease[1]. While Parkinson’s disease is traditionally recognized as a disorder primarily affecting the dopamine system in the brain, growing evidence suggests that the serotonin system is also significantly impacted, potentially even before dopamine neurons are affected.

Understanding Prodromal Parkinson’s Disease

The prodromal phase of Parkinson’s disease may last for years or even decades before the characteristic motor symptoms of tremor, rigidity, and slowness of movement become apparent[1]. During this time, individuals may experience subtle non-motor symptoms such as changes in mood, sleep disturbances, or constipation, which are thought to be related to alterations in the serotonin system.

By using (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE to visualize 5-HT4 receptors in SNCA mutation carriers, researchers can investigate whether changes in this particular component of the serotonin system occur during the prodromal phase[1]. This information could help explain some of the early non-motor symptoms of Parkinson’s disease and potentially identify new targets for therapeutic intervention.

Genetic Risk and Brain Changes

The focus on individuals with SNCA gene mutations is particularly valuable because these individuals have a known genetic predisposition to developing Parkinson’s disease[1]. Studying this population allows researchers to observe brain changes that are likely related to disease development rather than other factors that might affect the general population.

The Phase 4 designation of this trial indicates that the radiotracers being used, including (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE, have already undergone extensive safety testing and are approved for use[1]. This phase of research typically focuses on gathering additional information about the substance’s use in specific populations or for particular applications, such as studying prodromal Parkinson’s disease in this case.

Implications for Future Research

The results of this trial using (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE may have several important implications[1]. If significant differences in 5-HT4 receptor binding are found between SNCA mutation carriers and healthy controls, this could support the development of new diagnostic tools for identifying individuals in the earliest stages of Parkinson’s disease.

Additionally, understanding how the serotonin system changes during the prodromal phase could inform the development of new therapeutic strategies aimed at slowing or preventing disease progression[1]. Current treatments for Parkinson’s disease primarily target the dopamine system and are typically started only after motor symptoms appear. Interventions targeting the serotonin system might offer new opportunities for earlier treatment.

Contribution to Parkinson’s Disease Research

This clinical trial contributes to a growing body of research aimed at understanding Parkinson’s disease as a multi-system disorder that affects various neurotransmitter systems in the brain[1]. The use of advanced imaging techniques with radiotracers like (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE allows researchers to study these systems in living individuals, providing insights that cannot be obtained through other methods.

The SerIAL-PD study represents a comprehensive approach to investigating the serotonin system by examining both the 5-HT4 receptor (using (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE) and the serotonin transporter (using [11C]DASB) in the same participants[1]. This dual-tracer approach provides a more complete picture of serotonin system function and how it may be altered in individuals at risk for Parkinson’s disease.

Trial ID Phase Condition Studied Status Enrollment Primary Outcome
2024-516610-38-00 Phase 4 Parkinson’s disease, Prodromal phase of Parkinson’s disease Authorised 50 Compare PET-binding potential of [11C]SB207145 to 5-HT4 receptor between SNCA mutation carriers and healthy controls

FAQ

  • What is being studied in clinical trials with (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE? Clinical trials are using (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE as a radiotracer in PET scans to study changes in the brain's serotonin system. Specifically, researchers are investigating how the serotonin receptor 5-HT4 is affected during the early, prodromal phase of Parkinson's disease in people who carry SNCA gene mutations.
  • Who can participate in these clinical trials? The trials are enrolling two groups of participants: people who carry mutations in the SNCA gene but do not yet have Parkinson's disease symptoms, and healthy control participants without the SNCA mutation or Parkinson's disease. The study plans to enroll approximately 50 participants total.
  • What phase are these clinical trials in? The clinical trial investigating (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE is in Phase 4. This means the radiotracer has already been approved and is being studied for additional information about its use in specific populations or conditions.
  • What conditions are being studied in these trials? The trials are focused on Parkinson's disease, particularly the prodromal phase, which is the early stage before obvious motor symptoms appear. Researchers are studying people at risk for developing Parkinson's disease due to genetic mutations to understand how brain changes occur before the disease fully develops.
  • How is (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE administered in these trials? The substance is administered as an intravenous bolus injection or IV infusion at a dose of 74 MBq/ml. It is used together with another radiotracer called 11C-DASB during PET imaging procedures to visualize different parts of the serotonin system in the brain.

Ongoing Clinical Trials on (1-(11C)METHYLPIPERIDIN-4-YL)METHYL 5-AMINO-6-CHLORO-1,4-BENZODIOXINE-8-CARBOXYLATE

  • Study of serotonin system changes in early Parkinson’s disease using [11C]DASB and [11C]SB207145 PET imaging in people with SNCA gene mutations

    Not yet recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France

Glossary

  • PET scan: Positron Emission Tomography is an imaging test that uses radioactive substances to show how organs and tissues are functioning in the body.
  • Radiotracer: A radioactive substance used in medical imaging that helps doctors see specific structures or processes inside the body.
  • Prodromal phase: The early stage of a disease before the main symptoms appear, when subtle changes are beginning to occur in the body.
  • SNCA gene mutation: A change in the alpha-synuclein gene that can increase the risk of developing Parkinson's disease.
  • Serotonin system: A network in the brain involving serotonin, a chemical messenger that affects mood, sleep, and movement.
  • 5-HT4 receptor: A specific type of protein in the brain that responds to serotonin and plays a role in various brain functions.
  • SERT: Serotonin transporter, a protein that moves serotonin between brain cells and helps regulate serotonin levels.
  • Binding potential: A measurement that shows how much a radiotracer attaches to its target in the brain, indicating the amount of that target present.
  • MBq/ml: Megabecquerels per milliliter, a unit measuring the amount of radioactivity in a solution.
  • Intravenous bolus injection: A method of giving medication or substances directly into a vein as a single, rapid dose.

References

  1. https://clinicaltrials.gov/study/2024-516610-38-00