start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=e72549 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infections. However, even when administered at the dose specified in the package insert, there is significant interindividual variability in the plasma concentrations of ganciclovir (GCV). In addition, correlations have been reported between the area under the concentration?time curve and therapeutic efficacy or adverse events. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy.
Objective: This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV infections is associated with the successful completion rate of treatment without severe hematological adverse effects.
Methods: This phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital, who will receive oral VGCV as preemptive therapy for CMV infections. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary end point will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without severe hematological adverse events. The secondary end points will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, this study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and nudix hydrolase 15 (NUDT15) genetic polymorphisms. The correlation between GCV plasma concentrations obtained from regular venous blood and blood concentrations will be examined using dried blood spots.
Results: This study began with patient recruitment in September 2024, with 5 participants enrolled as of June 16, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027.
Conclusions: This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy.
Trial Registration: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.mhlw.go.jp/latest-detail/jRCTs051240080
International Registered Report Identifier (IRRID): DERR1-10.2196/72549 en-copyright= kn-copyright= en-aut-name=TamuraNaoki en-aut-sei=Tamura en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoharaKotaro en-aut-sei=Itohara en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaYo en-aut-sei=Ueda en-aut-mei=Yo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmuraTomohiro en-aut-sei=Omura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaneToshiyasu en-aut-sei=Sakane en-aut-mei=Toshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaegusaJun en-aut-sei=Saegusa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=2 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=3 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, Kobe Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=valganciclovir kn-keyword=valganciclovir en-keyword=ganciclovir kn-keyword=ganciclovir en-keyword=cytomegalovirus kn-keyword=cytomegalovirus en-keyword=therapeutic drug monitoring kn-keyword=therapeutic drug monitoring en-keyword=preemptive therapy kn-keyword=preemptive therapy en-keyword=dried blood spots kn-keyword=dried blood spots END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=e60943 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250729 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Usefulness of Interventions Using a Smartphone Cognitive Behavior Therapy Application for Children With Mental Health Disorders: Prospective, Single-Arm, Uncontrolled Clinical Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The prevalence of mental health disorders among children in Japan has increased rapidly, and these children often show depressive symptoms and reduced quality of life (QOL). We previously developed a smartphone-based self-monitoring app to deliver cognitive behavioral therapy (CBT), implemented it in healthy children, and reported its effectiveness for health promotion.
Objective: This study aims to examine the usefulness of the CBT app for improvement in depressive symptoms and QOL in children with mental health disorders.
Methods: The participants were 115 children with mental health disorders (eg, school refusal, orthostatic hypotension, eating disorders, developmental disorders, among others) and aged 12]18 years. The CBT app?based program comprised 1 week of psychoeducation followed by 1 week of self-monitoring. After reading story-like scenarios, participants created a self-monitoring sheet with 5 panels: events, thoughts, feelings, body responses, and actions. All participants received regular mental health care from physicians in addition to the app-based program. To evaluate the participantsf depressive symptoms and QOL, Patient Health Questionnaire for Adolescents (PHQ-9A), Depression Self-Rating Scale for Children (DSRS-C), and Pediatric Quality of Life Inventory (PedsQL) were measured at the beginning of the intervention, and at 2 and 6 months thereafter. Questionnaire for Triage and Assessment with 30 items (QTA30), and Rosenberg Self-Esteem Scale (RSES) were also used to measure their health and self-esteem. Participants were divided into 4 groups on the basis of the PHQ-9A score (above or below the cutoff; PHQ-9A?5 or PHQ-9A<5) and completion or noncompletion of the CBT app?based program (app [+] or app [-]). The primary outcome was improvement in the DSRS-C score, and secondary outcomes were improvement in other psychometric scales including PedsQL, QTA30, and RSE. A paired-samples t test was used for statistical analysis. The Medical Ethics Committee of Fukuoka University Faculty of Medicine (approval U22-05-002) approved the study design.
Results: There were 48, 18, 18, and 7 participants in the PHQ-9A?5 app (+), PHQ-9A?5 app (-), PHQ-9A<5 app (+), and PHQ-9A<5 app (-) groups, respectively. A total of 24 participants dropped out. No improvement in the DSRS-C score was observed in all groups. However, PedsQL scores improved significantly at 2 and 6 months in the PHQ-9A<5 app (+) group (t17=6.62; P<.001 and t17=6.11; P<.001, respectively). There was a significant positive correlation between the PHQ-9A scores and the number of self-monitoring sheets completed.
Conclusions: The CBT app was useful for improving PedsQL scores of children with mental health disorders. However, a higher-intensity CBT program is necessary for more severely depressed children.
Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046775; center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053360 en-copyright= kn-copyright= en-aut-name=NagamitsuShinichiro en-aut-sei=Nagamitsu en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakutaRyoichi en-aut-sei=Sakuta en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshiiRyuta en-aut-sei=Ishii en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoyanagiKenshi en-aut-sei=Koyanagi en-aut-mei=Kenshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HabukawaChizu en-aut-sei=Habukawa en-aut-mei=Chizu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaTakashi en-aut-sei=Katayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoMasaya en-aut-sei=Ito en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanieAyako en-aut-sei=Kanie en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtaniRyoko en-aut-sei=Otani en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitajimaTasuku en-aut-sei=Kitajima en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsubaraNaoki en-aut-sei=Matsubara en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TanakaChie en-aut-sei=Tanaka en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiChikako en-aut-sei=Fujii en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShigeyasuYoshie en-aut-sei=Shigeyasu en-aut-mei=Yoshie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsuokaMichiko en-aut-sei=Matsuoka en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KakumaTatsuyuki en-aut-sei=Kakuma en-aut-mei=Tatsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HorikoshiMasaru en-aut-sei=Horikoshi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Pediatrics, Faculty of Medicine, Fukuoka University kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=4 en-affil=Department of Pediatrics & Child Health, Kurume University, School of Medicine kn-affil= affil-num=5 en-affil=Nagasaki Prefectural Center of Medicine and Welfare for Children kn-affil= affil-num=6 en-affil=Department of Pediatric Allergy, Minami Wakayama Medical Center kn-affil= affil-num=7 en-affil=L2B Inc kn-affil= affil-num=8 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= affil-num=9 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= affil-num=10 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=11 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=12 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=13 en-affil=Child Development and Psychosomatic Medicine Center, Dokkyo Medical University Saitama Medical Center kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neuropsychiatry, Kurume University School of Medicine kn-affil= affil-num=18 en-affil=Biostatistics Center, Kurume University kn-affil= affil-num=19 en-affil=National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry kn-affil= en-keyword=smartphone kn-keyword=smartphone en-keyword=cognitive behavioral therapy kn-keyword=cognitive behavioral therapy en-keyword=application kn-keyword=application en-keyword=adolescent kn-keyword=adolescent en-keyword=youth kn-keyword=youth en-keyword=teen kn-keyword=teen en-keyword=pediatric kn-keyword=pediatric en-keyword=mental health kn-keyword=mental health en-keyword=psychoeducation kn-keyword=psychoeducation en-keyword=self-monitoring kn-keyword=self-monitoring en-keyword=questionnaire kn-keyword=questionnaire en-keyword=depressive symptoms kn-keyword=depressive symptoms en-keyword=effectiveness kn-keyword=effectiveness en-keyword=Japan kn-keyword=Japan en-keyword=statistical analysis kn-keyword=statistical analysis en-keyword=single-arm uncontrolled study kn-keyword=single-arm uncontrolled study en-keyword=mobile phone kn-keyword=mobile phone END