124

Advanced Clinical Research Center

Division of Advanced Medicine Promotion
先端医療開発推進分野

ProfessorFumitaka Nagamura, M.D., D.M.Sc.
Associate Professor Masanori Nojima, M.D., Ph.D., M.P.H.

教 授
准教授

博士（医学）
博士（医学）

長野村島文
正孝寛

Our mission is to assist the development of translational research. For this purpose,
it is critical to discover new “seeds” and to eradicate blockades until the clinicalutilization. We also assist the conduct of clinical trials at IMSUT Hospital. At IMSUT
Hospital, we work together with the staffs of Center for Translational Research.
Concurrently, to concur blockades on translational research, we have beenengaging in research on regulatory science and biostatistics.

1. Assistance of Clinical Trials/TRs at Research
Hospital
Masanori Nojima, Fumitaka Nagamura
At IMSUT Hospital, we work together with thestaffs of Center for Translational Research. The assistance of Translational (Clinical) Research Coordinators is indispensable for the conduct of clinical trials,
especially for TR. The activities of Coordinators are
the results of the collaboration between Division ofAdvanced Medicine Promotion and Center for Translational Research. In 2023, we supported 4 sponsor-investigator clinical trials.
2. Approach for epigenome and multi-omics research by methodology of bioinformatics andbiostatistics
Masanori Nojima
Epigenome and multi-omics research using clinical samples in collaborative study or public databaseof comprehensive omics-analysis. We are now focusing on the multi-omics approach integrating DNA
methylation, mRNA expression, and miRNA, andbuilding statistical models to assess functional link-age.
3. Statistical consulting for basic research
Masanori Nojima
For basic researchers, we suggest exploratory statistical approach and molecular epidemiological approach.
4. Statistics and Quality control in Clinical Trials
Masanori Nojima, Mitsumi Tokunaga, Fumitaka
Nagamura
We have planned and performed data management, monitoring, and statistical works in clinical trials.
[Data management]: Planning, EDC and CRF preparation, registration, allocation, database management,
data cleaning, coding[Monitoring]: Monitoring for drug management[Statistics]: Planning and perform for statistical analyses, Sample size calculation.

125
5. A review of criteria strictness in “Toxicity Grading Scale for Healthy Adult and Adolescent
Volunteers Enrolled in Preventive Vaccine
Clinical Trials”
Masanori Nojima, Fumitaka Nagamura
To assess safety in vaccine development, stricter
grading scales, such as the “Toxicity Grading Scalefor Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” issued bythe U.S. Food and Drug Administration (FDA grading scale), are required. However, concern exists that
their strictness may lead to an overestimation of someadverse events (AEs). We analyzed the details of AEs
in a phase I clinical trial of a preventive vaccine forinfectious diseases. In this trial, we observed the highoccurrence of Grade 1 or greater AEs in hemoglobinchanges from baseline value, and hypernatremia, andhypokalemia by FDA grading scale. The range considered as non-AE according to the FDA grading
scale shifted or became narrower when compared toreference intervals, especially for a Japanese cohort.

Regarding a decrease in hemoglobin from baseline,
the criterion of “any decrease” used for a Grade 1 AE
was too strict and we suggest this be omitted. Upperand lower limits of AE criteria for sodium and potassium should be equal to, or 10–20% above, the reference interval consistent with other toxicities determined by laboratory tests. Consideration should begiven to the issues surrounding the criteria that determine AEs before conducting clinical trials.
6. Approach for epigenome and multi-omics research by methodology of bioinformatics andbiostatistics
Masanori Nojima
Epigenome and multi-omics research using clinical samples in collaborative study or public databaseof comprehensive omics-analysis. We are now focusing on the multi-omics approach integrating DNA
methylation, mRNA expression, and miRNA, andbuilding statistical models to assess functional linkage.

Publications
1.		Motoki Amai, Masanori Nojima, Yoshikazu Yuki,Hiroshi Kiyono, Fumitaka Nagamura. A review ofcriteria strictness in “Toxicity Grading Scale for
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials”. Vaccine. 2023 Aug 31;41(38):5622-5629. doi: 10.1016/j.
vaccine.2023.07.072. Epub 2023 Aug 1.
2.		Tokiko Nagamura-Inoue , Fumitaka Nagamura .
Umbilical cord blood and cord tissue banking assomatic stem cell resources to support medical cellmodalities. Inflamm Regen 2023 Dec 5;43(1):59.
doi: 10.1186/s41232-023-00311-4.
3.		Tokiko Nagamura-Inoue, Seiko Kato, Yuho Najima, Masamichi Isobe, Noriko Doki, Hisashi
Yamamoto, Naoyuki Uchida, Atsuko Takahashi,
Akiko Hori, Masanori Nojima, Kazuteru Ohashi,
Fumitaka Nagamura, Arinobu Tojo. Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells forsteroid-resistant acute graft-versus-host disease.
Int J Hematol. 116(5):754-769, 2023.
4.		Miyagami T, Nishizaki Y, Imada R, Yamaguchi K,Nojima M, Kataoka K, Sakairi, M, Aoki N, Furusaka T, Kushiro S, Yang KS, Morikawa T, Tohara H,Naito T. Dental Care to Reduce Aspiration Pneumonia Recurrence: A Prospective Cohort Study.
Int Dent J. 2024 Jan 13:S0020-6539(23)00974-7. doi:
10.1016/j.identj.2023.11.010. Epub ahead of print.
5.		Miura S, Kurimoto Y, Maruyama R, Nojima M,
Sasaki K, Masuda T, Nishioka N, Iba Y, Kawaharada N, Naraoka S. Initial two-day blood pressuremanagement after endovascular aneurysm repair

improves midterm outcomes by reducing the incidence of early type II endoleak. J Vasc Surg. 2023
Oct 10:S0741-5214(23)02081-5. doi: 10.1016/j.
jvs.2023.10.003. Epub ahead of print. PMID:37827245.
6.		Adachi Y, Nojima M, Mori M, Yamano HO, Sasaki
Y, Nakase H, Lin Y, Wakai K, Tamakoshi A; for
JACC study. Association of serum superoxide dismutase activity and the incidence of colorectal
cancer in a nested case-control study. Cancer Epidemiol. 2023 Sep 23;87:102455. doi: 10.1016/j.
canep.2023.102455. Epub ahead of print. PMID:37748209.
7.		Kazama T, Ando K, Ueno N, Fujiya M, Ito T,Maemoto A, Ishigami K, Nojima M, Nakase H.
Long-term effectiveness and safety of infliximab-biosimilar: A multicenter Phoenix retrospective cohort study. PLoS One. 2023 Sep 12;18(9):e0288393. doi: 10.1371/journal.pone.0288393. PMID:37699041; PMCID:
8.		Nasuno M, Shimazaki H, Nojima M, Hamada T,Sugiyama K, Miyakawa M, Tanaka H. Serum leucine-rich alpha-2 glycoprotein levels for predicting active ultrasonographic findings in intestinal
lesions of patients with Crohn’s disease in clinicalremission. Medicine (Baltimore). 2023 Aug 11;102(32):e34628. doi: 10.1097/MD.0000000000034628.
PMID: 37565885; PMCID: PMC10419375.
9.		Nishizaki Y, Kuroki H, Ishii S, Ohtsu S, WatanabeC, Nishizawa H, Nagao M, Nojima M, Watanabe
R, Sato D, Sato K, Kawata Y, Wada H, Toyoda G,
Ohbayashi K. Determining Optimal Intervals for

126
In-Person Visits During Video-Based Telemedicine Among Patients With Hypertension: Cluster
Randomized Controlled Trial. JMIR Cardio. 2023

Jun 8;7:e45230. doi: 10.2196/45230.
37161483; PMCID: PMC10288346.

PMID: