Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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 \[ULN\])
- 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 CYP1A2, CYP2C8, CYP2B6, CYP3A4, 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
