Key Effects of Cofrogliptin on Beta-cell Function in Adults With Latent Autoimmune Diabetes (LADA): A Single-Center, Randomized, Controlled Trial - KOLA Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Change From Baseline in 2-hour Mixed-Meal Tolerance Test (MMTT) C-peptide Area Under the Curve (AUC)
研究概览
简要总结
This single-center, randomized, open-label, controlled study aims to evaluate the effect of cofrogliptin on pancreatic β-cell function in adults with latent autoimmune diabetes in adults (LADA). Following a screening period of up to 6 weeks, 84 eligible participants will be randomized in a 1:1 ratio via a sealed-envelope method, stratified by baseline GADA titer (≥0.3 vs <0.3). Participants will be assigned to one of two treatment arms: (1) metformin (with or without insulin) plus vitamin D3, or (2) metformin (with or without insulin) plus vitamin D3 and cofrogliptin. Cofrogliptin will be administered orally at a dose of 10 mg once every 2 weeks, and vitamin D3 at 2000 IU once daily, for a total treatment duration of 52 weeks. Study visits are planned at baseline and at Weeks 12, 26, 38, and 52, during which mixed-meal tolerance tests (MMTT) and other protocol-specified assessments will be conducted.
详细描述
Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes characterized by the progressive destruction of pancreatic beta cells. Preclinical and clinical evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors and vitamin D possess immunomodulatory effects that may help preserve residual beta-cell function. Cofrogliptin is a novel, ultra-long-acting DPP-4 inhibitor.
This study will enroll patients with LADA who will first enter a screening period. Eligible participants will be randomized (1:1) into two parallel arms on Day 1. The experimental group will receive cofrogliptin and vitamin D3 in addition to their background therapy. The active comparator group will receive vitamin D3 plus background therapy. Background therapy includes metformin, with insulin permitted and adjusted per investigator's judgment. Follow-up clinic visits are scheduled at Weeks 12, 26, 38, and 52. Efficacy will be assessed through MMTT-derived C-peptide and glucose measurements, as well as other glycemic indices. Safety will be monitored through the recording of adverse events, laboratory tests, and vital signs throughout the 52-week treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Voluntarily signed informed consent.
- •2. Age 18 to 70 years, inclusive.
- •3. Diagnosed with LADA, defined as meeting all of the following:
- •(1) Meets 1999 WHO criteria for diabetes mellitus.
- •(2) Age at diagnosis of diabetes ≥ 18 years.
- •(3) Positive for at least one islet autoantibody (GADA, IA-2A, or ZnT8A).
- •(4) Did not require continuous insulin therapy for at least 6 months after diagnosis.
- •4. Stimulated C-peptide ≥ 200 pmol/L.
- •5. Glycated Hemoglobin (HbA1c) ≤ 9.0%.
- •6. For women of childbearing potential, must agree to use a highly effective method of contraception throughout the study.
排除标准
- •1. Pregnant, breastfeeding, or planning to become pregnant during the study.
- •2. Gestational diabetes or other specific types of diabetes.
- •3. Known hypersensitivity to Cogliptin, Vitamin D3, or their excipients.
- •4. Use of DPP-4 inhibitors, GLP-1 receptor agonists, or thiazolidinediones (TZDs) within 8 weeks prior to randomization.
- •5. Hypercalcemia (serum calcium above the upper limit of the normal range).
- •6. Systemic corticosteroid therapy (oral or IV) for more than 7 consecutive days within 6 months prior to screening.
- •7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN), or total bilirubin > 2 times ULN.
- •8. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m².
- •9. History of acute diabetic complications such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state.
- •10. History of pancreatitis or pancreatic surgery.
- •11. New York Heart Association (NYHA) class III or IV congestive heart failure, or known left ventricular ejection fraction (LVEF) < 40%.
- •12. History of malignancy.
- •13. Severe psychiatric illness.
- •14. History of alcohol or illicit drug dependence.
- •15. Any other severe systemic disease that the investigator deems unsuitable for enrollment.
研究组 & 干预措施
Cofrogliptin + Vitamin D3 + Background Therapy
Participants will receive Cofrogliptin (10 mg orally every 2 weeks) and Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), over a period of 52 weeks.
干预措施: Cofrogliptin (Drug)
Cofrogliptin + Vitamin D3 + Background Therapy
Participants will receive Cofrogliptin (10 mg orally every 2 weeks) and Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), over a period of 52 weeks.
干预措施: Insulin (Drug)
Vitamin D3 + Background Therapy
Participants will receive Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), for a total duration of 52 weeks.
干预措施: Insulin (Drug)
Vitamin D3 + Background Therapy
Participants will receive Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), for a total duration of 52 weeks.
干预措施: Metformin (Drug)
Cofrogliptin + Vitamin D3 + Background Therapy
Participants will receive Cofrogliptin (10 mg orally every 2 weeks) and Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), over a period of 52 weeks.
干预措施: Vitamin D3 (Drug)
Cofrogliptin + Vitamin D3 + Background Therapy
Participants will receive Cofrogliptin (10 mg orally every 2 weeks) and Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), over a period of 52 weeks.
干预措施: Metformin (Drug)
Vitamin D3 + Background Therapy
Participants will receive Vitamin D3 (2000 IU orally once daily), in addition to background therapy consisting of metformin (with or without insulin), for a total duration of 52 weeks.
干预措施: Vitamin D3 (Drug)
结局指标
主要结局
Change From Baseline in 2-hour Mixed-Meal Tolerance Test (MMTT) C-peptide Area Under the Curve (AUC)
时间窗: Baseline, Week 52
Change from baseline in the area under the curve from 0 to 120 minutes (AUC0-120) for serum C-peptide during a mixed-meal tolerance test (MMTT), calculated using the trapezoidal rule from C-peptide measured at 0, 60, and 120 minutes.
次要结局
- Change From Baseline in 2-hour MMTT C-peptide AUC at Weeks 12, 26, and 38(Baseline, Week 12, Week 26, Week 38)
- Change From Baseline in Fasting C-peptide (FCP)(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in 60-Minute Post-Meal C-peptide(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in 120-Minute Post-Meal C-peptide(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Glycated Hemoglobin (HbA1c)(Baseline, Week 26, Week 52)
- Proportion of Participants Achieving HbA1c < 7.0%(Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Mean Daily Insulin Dose(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Homeostatic Model Assessment of β-cell function (HOMA-β)(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Glutamic Acid Decarboxylase Autoantibody (GADA) Titers(Baseline, Week 52)
- Change From Baseline in Insulinoma-Associated Antigen-2 Autoantibody (IA-2A) Titers(Baseline, Week 52)
- Change From Baseline in Zinc Transporter 8 Autoantibody (ZnT8A) Titers(Baseline, Week 52)
- Change From Baseline in Body Weight(Baseline, Week 12, Week 26, Week 38, Week 52)
- Change From Baseline in Body Mass Index (BMI)(Baseline, Week 12, Week 26, Week 38, Week 52)
研究者
Zhiguang Zhou
Director, National Clinical Research Center for Endocrine and Metabolic Diseases
Second Xiangya Hospital of Central South University