Development and Clinical Application of [11C]Verapamil-PET

Development and Clinical Application of [11C]Verapamil-PET, a Surrogate Marker on P-glycoprotein Expression

The major hypothesis explaining drug resistance is overexpression of p-glycoprotein at the target lesion. Based on several studies, p-glycoprotein (P-gp) has an important role in neurologic diseases, especially in drug resistant epilepsy. But there is no surrogate marker that can quantify the expression of P-gp because of the difficulty in measuring substances in the neurologic system and the lack of clinical trials. Here, the investigators use a novel non-invasive [11C] -verapamil Brain PET and SPAM analytic method as a surrogate marker for quantifying the expression of p-glycoprotein.

Study Overview

• Status: Unknown
• Conditions: Epilepsy
• Intervention / Treatment: Drug: [11C] -verapamil PET

Detailed Description

A pilot study on healthy volunteers and a case-control study on patients with drug resistant epilepsy and drug sensitive epilepsy is performed. The investigators compare the whole brain SUV in each group (normal control, drug resistant epilepsy, drug sensitive epilepsy) and the asymmetry by the standardized uptake value(SUV) of ipsilateral areas and contralateral areas.

[11C] -verapamil PET will be used as a surrogate marker of P-gp expression in patients with epilepsy, and will be an important prognostic factor of individualized drug therapy. Also, it can be used as a biomarker in checking of the drug efficacy of novel medications. Furthermore, by localizing epileptogenic zones for patients, [11C] -verapamil PET could contribute in improving the prognosis of surgical treatment in drug resistant epilepsy.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Sang Kun Lee, MD, PhD; Email: sangkun2923@gmail.com
    • Principal Investigator: Sang Kun Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy controls ( age range 20-45 years)
• Patient age (> 15), diagnose as epilepsy

Exclusion Criteria:

• Subjects who take medicines that affect on the function of p-glycoproteins
• Pregnancy or subject who feed the breast milk
• Subjects who had severe renal disease or liver disease
• Subjects who need treated by immunosuppressant or take immunosuppressant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group (healthy persons); Normal controls take a [11C] -verapamil PET scan. While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.	Drug: [11C] -verapamil PET; While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.; Other Names: VPM PET
Active Comparator: Patients with drug-resistant epilesy; Patients with drug-resistant epilepsy take a [11C] -verapamil PET scan. While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.	Drug: [11C] -verapamil PET; While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.; Other Names: VPM PET
Active Comparator: Patients with drug-sensitive epilepsy; Patients with drug-sensitive epilepsy take a [11C] -verapamil PET scan. While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.	Drug: [11C] -verapamil PET; While P-gp inhibitor (Cyclosporin A, 2.5mg/kg/hr during 2hours, intravenous) is infused, PET scans were done using [11C] -verapamil, a substrate of P-gp.; Other Names: VPM PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measured Asymmetric index[(SUV in Right regions - SUV in Left regions)/(SUV in Right regions+ SUV in left regions)] in all three groups	Comparing with Asymmetry index in each groups	first visit day

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with side effect of cyclosporine and [11C]-verapamil PET	During and after the drug injection, During and after the PET Scan [first visit day]

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Sang Kun Lee, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): May 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: May 19, 2014
• First Posted (Estimate): May 22, 2014

Study Record Updates

• Last Update Posted (Estimate): May 22, 2014
• Last Update Submitted That Met QC Criteria: May 19, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Verapamil
• Other Study ID Numbers: 0720130520