METabolic MODulation to Enhance Insulin Sensitivity and Mitochondrial Function in Type 1 Diabetes (MetMod-T1D)
Purpose
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.
Conditions
- Type 1 Diabetes (T1D)
- Metabolic Diseases
- Glucose Metabolism Disorders
- Endocrine System Diseases
- Autoimmune Diseases
- Immune System Diseases
- Diabetes Melletus, Type 1
- Nutritional and Metabolic Diseases
- Combination Therapy
Eligibility
- Eligible Ages
- Between 18 Years and 69 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adults ≥18 years to <70 years of age with established T1D (duration ≥1 year) 2. Currently on insulin therapy (multiple daily injections or insulin pump) 3. HbA1c <9.5% 4. BMI 18.5-40 kg/m2 5. On stable dose of RASB or statin, if indicated 6. Willing and able to comply with all study procedures
Exclusion Criteria
- History of pancreatic disease (including pancreatitis) or pancreatic surgery 2. History of cardiovascular disease or stroke within the past 6 months 3. History of heart failure per New York Heart Association criteria 4. History of severe edema or salt restriction requirement 5. Biliary disease or pathologies that may alter enterohepatic circulation of bile acids 6. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² 7. Liver disease (ALT/AST >3x upper limit of normal [ULN]) or severe hepatic impairment (defined as Child-Pugh Class C) 8. Pregnancy, breastfeeding, or planning pregnancy during the study period 9. Known hypersensitivity to study drug components 10. Abnormal baseline ECG 11. Use of off label medications that affect insulin sensitivity within the past 1 month (e.g., metformin, GLP-1RA, SGLT2i, pioglitazone) 12. Chronic use of anticoagulants 13. 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 14. Use of substrates of CYP2C9, Organic Anion transporter 1, P-glycoprotein, and Breast Cancer Resistance Protein 15. History of severe hypoglycemia requiring assistance within the past 3 months 16. History of diabetic ketoacidosis (DKA) within the past 3 months 17. Personal or family history of breast cancer or ovarian cancer 18. Current participation in another clinical trial 19. Any condition(s) found by the study team and confirmed with the Investigator that make it unsafe to participate
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Placebo Comparator 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. |
|
Recruiting Locations
Seattle, Washington 98109
More Details
- Status
- Recruiting
- Sponsor
- University of Washington
Detailed 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.