Safety and Dose-Response of Bletilla Formosana in Prediabetic Subjects

Official title

A Phase I/II Randomized, Double-Blind, Placebo-Controlled Pilot Trial Evaluating the Safety and Dose-Response of Bletilla Formosana in Prediabetic Subjects

Overview

This study evaluates the safety and preliminary efficacy of Bletilla formosana (BF), a traditional herbal medicine, in adults with prediabetes. Prediabetes is a high-risk condition where blood sugar levels are elevated, often leading to type 2 diabetes. While lifestyle changes are the standard treatment, researchers are exploring herbal supplements as a complementary way to support metabolic health. Preclinical research has shown that BF possesses anti-inflammatory properties and may help regulate blood glucose. Participants in this study will be randomly assigned to receive either a high dose of BF, a low dose of BF, or a placebo (an inactive substance) for 12 weeks. The total study duration is approximately 24 weeks, involving four clinic visits for blood tests and safety monitoring to see how BF affects blood sugar markers and inflammation.

Detailed description

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).

Interventions

• Drug Bletilla formosana (BF) powder
  A traditional Chinese medicinal herb (Taiwanese ground orchid). The raw material is derived from the approved botanical species and medicinal part listed in the Taiwan Herbal Pharmacopoeia.
• Other Placebo
  An inactive powder matching the appearance and dosage form of the BF powder, consisting of starch and caramel coloring.

Primary outcome measures

• Number of Participants with at Least One Treatment-Emergent Adverse Event (AE) [Time frame: From baseline to Week 24.]
• Number of Participants with Serious Adverse Events (SAEs) [Time frame: From baseline to Week 24]
• Change from Baseline in Fasting Plasma Glucose (FPG) (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Glycated Hemoglobin (HbA1c) (%) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [Time frame: Baseline, Week 6, Week 12, and Week 24.]

Secondary outcome measures (7)

• Change from Baseline in Tumor Necrosis Factor-alpha (TNF-α) (pg/mL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Interleukin-6 (IL-6) (pg/mL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in C-reactive protein (CRP) (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Total Cholesterol (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in High-Density Lipoprotein (HDL) (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Low-Density Lipoprotein (LDL) (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]
• Change from Baseline in Triglycerides (TG) (mg/dL) [Time frame: Baseline, Week 6, Week 12, and Week 24.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Taiwan · 3 centers

• Keelung Chang Gung Memorial Hospital — Keelung
• Linkou Chang Gung Memorial Hospital — Taoyuan
• Taoyuan Chang Gung Memorial Hospital — Taoyuan

Identifiers

NCT: NCT07704944 · 202500720A3C6002 · NSTC 114-2321-B-255-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗