Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial

Table 3 Objectives and procedures of the Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease (PERION) study

	Study time point (weeks)
	Screening period	Treatment period				Follow-up period
Study objectives	− 4	0	4	8	12	60
Primary objective
Change in ALT levels from baseline	○	○			○	○
Key secondary objective
Change in serum IgG antibody titer for P. gingivalis	○				○	○
Other secondary objectives
Change in blood endotoxin activity by EAA	○	○	○	○	○	○
Change in liver fat content using CAP and MRI-PDFF	○	○			○
Change in liver stiffness using VCTE and MRE	○	○			○
Change in oral bacterial counts using NGS and qPCR	○	○			○
Change in blood parameters for liver function (AST, GTT, ALP, and T-Bil)	○	○	○	○	○	○
Change in blood lipid parameters (T-Cho, LDL-C, TG, and HDL-C)	○	○	○	○	○	○
Change in blood parameters related with inflammation in NAFLD (ferritin, CK-18, TNF-α, IL-6, and h-CRP)		○			○
Change in blood parameters related with fibrotic marker in NAFLD (type IV collagen 7S)		○			○
Change in blood diabetic factors (blood glucose, insulin, and HOMA-IR)		○	○	○	○	○
Change in BMI	○	○	○	○	○	○
Assessment of periodontal treatment safety		○	○	○	○	○
Dropout ratio in each group		○	○	○	○	○
Tertiary objectives
Change in blood parameters for renal function (BUN, Cr, eGFR)	○	○	○	○	○	○
Change in HRQOL using SF-8™	○	○			○	○

All objectives will be compared between the periodontal scaling and root-planing treatment group and the tooth-brushing treatment group. ALP alkaline phosphatase, ALT alanine transaminase, AST aspartate transaminase, BMI body mass index, BUN blood urea nitrogen, CAP controlled attenuation parameter, CK-18 cytokeratin 18, Cr creatinine, EAA endotoxin activity assay, eGFR estimated glomerular filtration rate, FBS fasting blood sugar, GGT γ-glutamyltransferase, h-CRP high-sensitivity C-reactive protein, HDL-C high-density lipoprotein-cholesterol, HOMA-IR homeostasis model assessment of insulin resistance, HRQOL health-related quality of life, IL-6 interleukin-6, LDL-C low-density lipoprotein-cholesterol, MRE magnetic resonance elastography, MRI magnetic resonance imaging, NAFLD nonalcoholic fatty liver disease, NGS next-generation sequencer; PERION, PERIOdontal treatment for NAFLD, PDFF proton density fat fraction, qPCR quantitative polymerase chain reaction, SF-8 short form-8, T-Bil total bilirubin, T-Cho total cholesterol, TG triglycerides, TNF-α tumor necrosis factor-α

ISSN: 1745-6215