Safety and Dose-Response of Bletilla Formosana in Prediabetic Subjects

This is a single-center, Phase I/II, randomized, double-blind, placebo-controlled, parallel-design trial. The primary goal is to translate robust preclinical findings-where BF extract was shown to inhibit neutrophil-driven inflammation and improve glycemic parameters in animal models-into clinical evidence.

A total of 94 prediabetic subjects (defined by FPG 100-125 mg/dL or HbA1c 5.7%-6.4%) will be enrolled.

Participants will be randomized in a 2:2:1 ratio into one of the following three arms:

High-dose group: 3g Bletilla formosana powder daily. Low-dose group: 1.5g Bletilla formosana powder plus 1.5g placebo daily. Placebo group: 3g inactive placebo powder daily.

The study consists of three distinct phases:

Screening Phase: Up to 2 weeks for eligibility confirmation. Treatment Phase: 12 weeks of oral administration. Follow-up Phase: 12 weeks post-treatment to evaluate sustained efficacy and safety outcomes.

Phase I objectives focus on safety and tolerability, with adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0.

Phase II objectives explore preliminary efficacy through changes in fasting plasma glucose (FPG), HbA1c, and HOMA-IR.

Secondary endpoints include assessment of inflammatory biomarkers (TNF-α, IL-6, and CRP) and lipid profiles.

Clinical assessments, including 12-lead ECG and comprehensive laboratory testing, are scheduled at Screening, Week 6, Week 12 (end of treatment), and Week 24 (end of study).

Inclusion criteria

• Adults aged 30-70 years.
• Prediabetes defined by any of the following:
• Fasting Plasma Glucose (FPG) of 100-125 mg/dL, or
• Glycated hemoglobin (HbA1c) of 5.7%-6.4%.
• Willingness to provide written informed consent and comply with study procedures.

Exclusion criteria

• Established type 1 or type 2 diabetes mellitus, or recent use of oral antidiabetic agents or insulin (within 3 months).
• Abnormal liver function, defined as Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) exceeding 2-fold the upper reference limit (≥2 × ULN) at screening.
• Abnormal renal function, defined as serum creatinine (Cr) >1.5 mg/dL or Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m².
• Gastrointestinal disorders that may affect drug absorption, such as gastrostomy, enterostomy, severe chronic diarrhea, or malabsorption syndrome.
• Severe comorbidities within the past 6 months, including major stroke, myocardial infarction, major trauma, or major surgery.
• Recent use of medications (within 1 month) that may significantly alter blood glucose or lipids, such as systemic corticosteroids or non-stable doses of lipid-lowering agents.
• Malignant tumor under active treatment, or immunodeficiency/autoimmune disorders requiring immunosuppressive therapy.
• Psychiatric disorders or cognitive impairment that may affect protocol compliance.
• Active use of other investigational drugs within 3 months prior to screening.
• Pregnancy or lactation.