臨床研究等提出・公開システム

The clinical trial to evaluate the efficacy of [11C]K-2 in refractory epilepsy patients undergoing anterior temporal lobectomy

The clinical trial to evaluate the efficacy of [11C]K-2 in epilepsy patients

8

FAS 1 7 participants: male 2 (28.6%) / female 7 (71.4%), median age 43y.o. (21-58), seizure type complex partial seizure 5 (71.4%) / complex partial seizure + others 2 (28.6%)

8 participants registered, 4 completed, 4 not completed From March 2017 to Dec 2018, 8 participants were registered. All patients underwent preoperative AMPA-PET examinations, followed by epilepsy surgery. 4 participants discontinued prior to second AMPA-PET examinations. In one of them, the operation plan was changed immediately before surgery, leading to insufficient collection of surgical specimen, hence the discontinuation of the study. One of them was discontinued because of severe seizures several months after the operation, which resulted in irreversible impaired consciousness. One of them was discontinued because of hepatic dysfunction unrelated to study treatment. One of them was discontinued because of the patients issues. The main analyzes were performed on 7 cases in which a sufficient amount of surgical specimens were collected.

Adverse reaction related to study treatment were found 1 subject, Grade 1 high blood pressure (n=1) and Grade 1 headache (n=1).

Primary endpoint was the correlation between preoperative AMPA-PET imaging values (AMPA receptor density) and AMPA receptor biochemical quantification values (protein expression levels) in the same brain regions, and the correlation coefficient was calculated by the least squares method of the regression line. Using SUV, the correlation coefficient was 0.846 (90% CI = 0.418 - 0.958), and using BPnd imaging values, the correlation coefficient was 0.891 (90% CI =0.557 - 0.970). The following items were examined as secondary analysis. 1. Summary of postoperative seizure evaluation using classification of Engel classification and ILAE classification : No significant changes were observed in PET image values before and after surgery in comparison between patients showing seizure free and seizure remaining postoperatively. 2. Summary of preoperative AMPA receptor density classified by increase, unchanged, or decrease in postoperative antiepileptic drugs (number of oral medications and daily dose) : No change in preoperative AMPA receptor density was observed by each classification. 3. Summary of changes between preoperative values of AMPA receptor density obtained from [11C]K-2PET images of each unresected region (hippocampus/temporal lobe cortex region) on the resection side and those obtained at 6 to 12 months after surgery : The changes were -0.8835 to 0.0818 in SUV and -0.6988 to 0.1030 in BPnd, and in both cases, the AMPA receptor density did not change significantly before and after surgery. 4. Correlation between FDG-PET measurement values and preoperative AMPA receptor densities : The correlation coefficient of SUV showed a high negative correlation of -0.525 to -0.891. This result indicates the higher the AMPA receptor density, the lower the FDG-PET image value. 5. Correlation between changes in cognitive test values (intelligent test IQ, memory test MQ) and preoperative AMPA receptor densities obtained from [11C]K-2PET images : A positive correlation was found between verbal IQ and AMPA receptor density in the inferior temporal gyrus, and functional IQ and AMPA receptor density in the fusiform and middle temporal gyrus. In memory tests, following evaluation items showed positive correlation with AMPA receptor densities in indicated regions; verbal memory and middle temporal gyrus, attention/concentration and hippocampus, delayed regenerative ability and fusiform/middle temporal gyrus, general memory and middle temporal gyrus.

In the primary endpoint, we examined the specificity of AMPA-PET in the human brain and the correlation coefficient between the amount of AMPA receptor protein expressions in the surgical specimen and AMPA receptor densities showed a high value of 0.846 or 0.891. These results sugeest that AMPA receptor densities in the living human brain can be measured with high quantitativeness by AMPA-PET. [11C]K-2PET was generally safe.

Mar. 31, 2022

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs031180191

Miyazaki Tomoyuki

Yokohama City University Hospital

3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan

johney@yokohama-cu.ac.jp

Sano Akane

Yokohama City University, School of Medicine

3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan

+81-45-787-2579

akane@med.yokohama-cu.ac.jp

Complete

July. 20, 2016

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

other

1.refractory epilepsy patients(mesial temporal lobe epilepsy)
2.patinets for anterior temporal lobectomy(ATL)
3.patients who are without cerebral surgery on the same side of ATL
4.patients who are 20 years or older
5.patients who can consent to this study by oneself

1.patients who have significant abnormalities insides the brains
2.patients who have experienced the electric stimulation therapy
3.patients who undergo artificial dialysis
4.patients who have severe liver dysfunction
5.patients who have tatoo
6.claustrophobic patients
7.breast-feeding mothers, expecting mothers, females who desire to be a mother
8.patients who desire to bear a child within this study period
9.patients who take Fycompa
10.patients who underwent nuclear medicine examination within one-week before this registarion
11.patients who underwent other clinical trials using unapproved nuclear medicine examination within six month before this registarion
12.patients who underwent other clinical trials within 12 weeks before this registarion
13.patients whom study doctors consider unappropriate

Both

refractory epilepsy patients

Administration of unapproved drug

The correlation of the AMPA receptors densities examined by biochemical study and [11C]K-2 PET study

Efficacy
1)Engel classification and ILAE classification in evaluation of postoperative epileptic seizures
2)The density of AMPA receptors obtained from preoperative [11C]K-2 PET imaging, and FDG-PET values
3)The quantitative changes in cognitive function scores {intelligence quotient (IQ), memorial quotient (MQ)} around surgery
4)The quantitative changes in prescribed anti-epileptic drugs (the number of types, and the dose per day) after surgery
Safety
The adverse events occurred in patients during 7 days after PET scan

+81-45-370-7627

Jan. 18, 2019

none