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