METabolic MODulation to Enhance Insulin Sensitivity and Mitochondrial Function in Type 1 Diabetes (MetMod-T1D)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in whole-body insulin sensitivity (M-value) measured by hyperinsulinemic-euglycemic clamp
研究概览
简要总结
The study is a randomized, double-blind, parallel-group clinical trial to examine the effects of 24 weeks of oral AMX0035 (sodium phenylbutyrate + taurursodiol) versus placebo in 60 adults with Type 1 Diabetes (T1D) (n=30 per arm). Enrollment will be distributed equally between the University of Washington and Amsterdam University Medical Center/Diabetes Center Amsterdam. Participants will be recruited through diabetes research registries, local T1D clinics, and community outreach.
详细描述
This is a randomized, double-blind, parallel-group clinical trial to evaluate the effects of 24 weeks of oral AMX0035 (sodium phenylbutyrate + taurursodiol) versus placebo in 60 adults with type 1 diabetes (T1D) (n=30 per arm). Following screening and baseline assessments, eligible participants will be randomized 1:1 to receive either AMX0035 or placebo, with stratification by sex and body mass index (≥30 vs. <30 kg/m2). Participants will undergo comprehensive metabolic phenotyping at baseline and 24 weeks, including hyperinsulinemic-euglycemic clamp studies, body composition imaging, continuous glucose monitoring, and tissue biopsies (skeletal muscle and adipose) for assessment of mitochondrial function and biological markers. Participants, clinicians administering the intervention, and laboratory personnel analyzing the samples will remain blinded to treatment assignments throughout the study.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years to <70 years of age with established T1D (duration ≥1 year)
- •Currently on insulin therapy (multiple daily injections or insulin pump)
- •HbA1c <9.5%
- •BMI 18.5-40 kg/m2
- •On stable dose of RASB or statin, if indicated
- •Willing and able to comply with all study procedures
排除标准
- •History of pancreatic disease (including pancreatitis) or pancreatic surgery
- •History of cardiovascular disease or stroke within the past 6 months
- •History of heart failure per New York Heart Association criteria
- •History of severe edema or salt restriction requirement
- •Biliary disease or pathologies that may alter enterohepatic circulation of bile acids
- •Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m²
- •Liver disease (ALT/AST >3x upper limit of normal [ULN]) or severe hepatic impairment (defined as Child-Pugh Class C)
- •Pregnancy, breastfeeding, or planning pregnancy during the study period
- •Known hypersensitivity to study drug components
- •Abnormal baseline ECG
- •Use of off label medications that affect insulin sensitivity within the past 1 month (e.g., metformin, GLP-1RA, SGLT2i, pioglitazone)
- •Chronic use of anticoagulants
- •Use of bile acid sequestering agents, inhibitors of bile acid transporters, bile acid derivatives, aluminum-based antacids, probenecid, pan-HDAC inhibitors, phase 2 metabolizing enzymes (e.g., uridine diphosphate glucuronosyl transferases), phase 1 metabolizing enzymes other than cytochrome P450 enzymes (CYPs), and OATP1B3
- •Use of substrates of CYP2C9, Organic Anion transporter 1, P-glycoprotein, and Breast Cancer Resistance Protein
- •History of severe hypoglycemia requiring assistance within the past 3 months
- •History of diabetic ketoacidosis (DKA) within the past 3 months
- •Personal or family history of breast cancer or ovarian cancer
- •Current participation in another clinical trial
- •Any condition(s) found by the study team and confirmed with the Investigator that make it unsafe to participate
研究组 & 干预措施
Placebo
Participants will be instructed to take one packet of placebo daily for the first 2 weeks, followed by 1 packet twice a day (morning and evening) thereafter for ~6 months.
干预措施: Placebo (Drug)
AMX0035
Participants will be instructed to take one packet of AMX0035 daily for the first 2 weeks, followed by 1 packet twice a day (morning and evening) thereafter for ~6 months.
干预措施: AMX0035 (Drug)
结局指标
主要结局
Change in whole-body insulin sensitivity (M-value) measured by hyperinsulinemic-euglycemic clamp
时间窗: Baseline, 24 weeks
Evaluate the effect of 24 weeks of AMX0035 versus placebo on whole-body insulin sensitivity in T1D as assessed by gold-standard two-stage hyperinsulinemic-euglycemic clamp. * Two-stage hyperinsulinemic-euglycemic clamp studies will occur at baseline and 24 weeks. * Insulin sensitivity will be quantified using the M-value (glucose infusion rate), normalized to lean body mass measured by dual-energy X-ray absorptiometry (DXA) and insulin concentration.
次要结局
- Changes in glycemic control(Baseline, 24 weeks)
- Changes in body composition(Baseline, 24 weeks)
- Changes in immune and metabolic biomarkers(Baseline, 24 weeks)
- Changes in mitochondrial function(Baseline, 24 weeks)
- Establish the safety and tolerability of AMX0035 in adults with T1D(Duration of study)
研究者
Petter Bjornstad
Professor: Division of Metabolism, Endocrinology, and Nutrition
University of Washington