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.
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
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
Parallel
AMX0035
DrugAMX0035 sachets
Placebo
DrugPlacebo sachets
Change in whole-body insulin sensitivity (M-value) measured by hyperinsulinemic-euglycemic clamp
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.
Changes in glycemic control
Glycemic control will be evaluated via continuous glucose monitoring (CGM) and HbA1c.
Changes in body composition
Body composition, including total, regional, visceral, and hepatic fat, will be quantified using DXA and multiparametric MRI.
Changes in immune and metabolic biomarkers
* Circulating and peripheral blood mononuclear cell (PBMC)-based biomarkers of inflammation and oxidative stress will be measured. * Associations between these biological markers and insulin sensitivity or glycemic metrics will be examined using multivariable models.
Changes in mitochondrial function
Skeletal muscle and adipose tissue biopsies will be analyzed for ER stress, inflammation, and insulin signaling. Skeletal muscle tissue will also undergo assessment of mitochondrial function by ex vivo respiration.
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University of Washington
Lead sponsor
Breakthrough T1D
Collaborator
