Prediabetes
Conditions
Keywords
Prediabetes, Bletilla formosana, Traditional Chinese Medicine, Herbal Medicine, Glycemic Control, Anti-inflammatory, Dose-Response Relationship, Phase I/II Trial, Randomized Controlled Trial, Safety and Tolerability
Brief summary
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
DRUGBletilla 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.
OTHERPlacebo
An inactive powder matching the appearance and dosage form of the BF powder, consisting of starch and caramel coloring.
Sponsors
Chang Gung Memorial Hospital
National Science and Technology Council
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
To ensure blinding, the investigational product (BF powder) and the placebo (starch with caramel coloring) are identically packaged in standardized, light-blocking plastic bottles and labeled only with unique subject codes. All participants receive the same number of sachets (one in the morning and one in the evening) so that the appearance, dosage form, and administration frequency remain indistinguishable across all treatment arms. The randomization code is securely maintained by the Traditional Chinese Medicine Pharmacy and will not be disclosed to investigators or participants until database lock.
Intervention model description
This is a randomized, double-blind, 3-arm parallel trial. Participants are assigned in a 2:2:1 ratio to one of three groups: High-dose Bletilla formosana (BF), Low-dose BF, or Placebo. To maintain the blind, all participants follow an identical dosing schedule, taking one sachet in the morning and one sachet in the evening. The high-dose group receives two active BF sachets; the low-dose group receives one active BF sachet and one matching placebo sachet; and the placebo group receives two matching placebo sachets.
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Adults aged 30-70 years. 2. Prediabetes defined by any of the following: 3. Fasting Plasma Glucose (FPG) of 100-125 mg/dL, or 4. Glycated hemoglobin (HbA1c) of 5.7%-6.4%. 5. Willingness to provide written informed consent and comply with study procedures.
Exclusion criteria
1. Established type 1 or type 2 diabetes mellitus, or recent use of oral antidiabetic agents or insulin (within 3 months). 2. Abnormal liver function, defined as Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) exceeding 2-fold the upper reference limit (≥2 × ULN) at screening. 3. Abnormal renal function, defined as serum creatinine (Cr) \>1.5 mg/dL or Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m². 4. Gastrointestinal disorders that may affect drug absorption, such as gastrostomy, enterostomy, severe chronic diarrhea, or malabsorption syndrome. 5. Severe comorbidities within the past 6 months, including major stroke, myocardial infarction, major trauma, or major surgery. 6. 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. 7. Malignant tumor under active treatment, or immunodeficiency/autoimmune disorders requiring immunosuppressive therapy. 8. Psychiatric disorders or cognitive impairment that may affect protocol compliance. 9. Active use of other investigational drugs within 3 months prior to screening. 10. Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with at Least One Treatment-Emergent Adverse Event (AE) | From baseline to Week 24. | Incidence of all adverse events (AEs) graded by CTCAE v5.0. |
| Number of Participants with Serious Adverse Events (SAEs) | From baseline to Week 24 | Number of participants experiencing life-threatening or fatal events according to ICH-GCP definitions. |
| Change from Baseline in Fasting Plasma Glucose (FPG) (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | Change in fasting blood sugar levels to assess the preliminary glycemic efficacy of Bletilla formosana. |
| Change from Baseline in Glycated Hemoglobin (HbA1c) (%) | Baseline, Week 6, Week 12, and Week 24. | Assessment of average blood glucose control over time. |
| Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Baseline, Week 6, Week 12, and Week 24. | Calculated using fasting insulin and glucose levels to assess changes in insulin sensitivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Tumor Necrosis Factor-alpha (TNF-α) (pg/mL) | Baseline, Week 6, Week 12, and Week 24. | To evaluate the anti-inflammatory effects of Bletilla formosana. |
| Change from Baseline in Interleukin-6 (IL-6) (pg/mL) | Baseline, Week 6, Week 12, and Week 24. | To evaluate the anti-inflammatory effects of Bletilla formosana. |
| Change from Baseline in C-reactive protein (CRP) (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | To evaluate the anti-inflammatory effects of Bletilla formosana. |
| Change from Baseline in Total Cholesterol (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | Assessment of lipid profiles using standard laboratory methods |
| Change from Baseline in High-Density Lipoprotein (HDL) (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | Assessment of lipid profiles using standard laboratory methods. |
| Change from Baseline in Low-Density Lipoprotein (LDL) (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | Assessment of lipid profiles using standard laboratory methods. |
| Change from Baseline in Triglycerides (TG) (mg/dL) | Baseline, Week 6, Week 12, and Week 24. | Assessment of lipid profiles using standard laboratory methods. |
Countries
Taiwan
Contacts
CONTACTYuan-Chieh Yeh, MD
CONTACTYu-Chieh Peng, Bachelor
PRINCIPAL_INVESTIGATORYuan-Chieh Yeh, MD
Chang Gung Memorial Hospital
Outcome results
None listed