Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06072326
Other study ID # 17042
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date March 2024
Est. completion date March 2025

Study information

Verified date October 2023
Source University Medical Center Groningen
Contact Hiddo J Lambers Heerspink, Phd, PharmD
Phone +31-50-3617859
Email h.j.lambers.heerspink@umcg.nl
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The aim of this study is to test the hypothesis that sotagliflozin (SGLT1/2 inhibitor) and ambrisentan (ERA) combination therapy augments nephroprotection and mitigates fluid retention and ketogenesis in people with T1D through complementary and synergistic mechanisms of actions.


Description:

A phase 2, multicenter, randomized, open-label, cross-over trial will be conducted in male or female individuals (N=36) diagnosed with type 1 diabetes at least 6 months prior to informed consent aged between 18 and 65 years, Body Mass Index (BMI) ≥ 21 kg/m2, urinary albumin:creatinine ratio ≥ 50 mg/g and < 3000 mg/g, eGFR > 30 and <90 ml/min/1.73m2 and HbA1c between 6.5 and 10.0%. Patients have to be on stable RAAS inhibition for at least 4 weeks prior to screening. The study will consist of a screening visit, a 4-week run-in phase. After the run-in phase, the participant will be randomized to treatment of ambrisentan, sotagliflozin or their combination in random order. The duration of each treatment period is 4 weeks with study visits scheduled at 2 and 4 weeks in each treatment period. At the end of each treatment period patients proceed to a 4 weeks wash-out phase to study off drug effects. The total duration of the study for each participant after randomization is thus 24 weeks Interventions Ambrisentan 2.5 mg once daily; sotagliflozin 200mg once daily; combination of ambrisentan 2.5mg once daily and sotagliflozin 200mg once daily


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 36
Est. completion date March 2025
Est. primary completion date March 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - Willing and able to sign informed consent - Male or female individuals diagnosed with type 1 diabetes at least 6 months prior to informed consent - WOCBP must have a negative pregnancy test at screening and must not be lactating. - Male individuals must use highly effective method of contraception for the duration of the study (from the time they sign consent) and for 4 weeks after the last dose of study medication, or be able to provide proof of vasectomy. - Female individuals must use highly effective method of contraception for the duration of the study (from the time they sign consent) and for 4 weeks after the last dose of study medication, provide proof of hysterectomy or sterilization, or be deemed menopausal based on a FSH-test. - Age =18 and <65years, at the time of signing consent. - Body Mass Index = 21 kg/m2 - Urinary albumin:creatinine ratio = 50 mg/g and <3000 mg/g - eGFR > 30 and <90 ml/min/1.73m2 - Stable RAAS inhibition medication for at least 4 weeks prior to screening - HbA1c between 6.5 and 10.5% - Based on the Investigator's judgment participant must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed before randomization): - patient-led management and adjustment of insulin therapy - reliable approach to insulin dose adjustment for meals, such as carbohydrate counting - reliable and regular home-based blood glucose monitoring - established "sick day" management regimen Exclusion Criteria: - Diagnosis of type 2 diabetes - Treatment with an antihyperglycaemic agent (e.g., metformin, alpha-glucosidase inhibitors, pramlintide, glucagon-like peptide receptor agonist, etc.) within 3 months - Occurrence of severe hypoglycaemia involving coma/unconsciousness and/or seizure that required hospitalisation or hypoglycaemia-related treatment by an emergency physician or paramedic within 3 months - Hypoglycaemia unawareness based on Investigator judgement or frequent episodes of unexplained hypoglycaemia (2 or more unexplained episodes within 3 months) - Occurrence of diabetic ketoacidosis within 6 months prior to study enrolment - Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack within 6 months - Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g., immunocompromised patients, patients who might be at higher risk of developing urinary, genital or mycotic infections, patients with chronic viral infections, etc.) - Treatment with an SGLT2i within 30 days of Visit 1 - Diagnosis of severe edema (per investigator judgment) or heart failure (NYHC stage III or IV)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sotagliflozin
200 mg/day as a tablet
Ambrisentan
2.5 mg/day as a tablet
Ambrisentan and Sotagliflozin
2.5 mg/day Ambrisentan as a tablet in combination with 200 mg/day Sotagliflozin as a tablet

Locations

Country Name City State
Canada Institute de Recherches Cliniques de Montreal Montréal Quebec
Canada University of Toronto Toronto
Denmark Steno Diabetes Center Copenhagen Copenhagen
Finland University of Helsinki Helsinki Uusimaa
Netherlands Amsterdam University Academic Center Amsterdam Noord Holland
Netherlands University Medical Center Groningen Groningen
United States University of Colorado, Anschutz Medical Center Aurora Colorado

Sponsors (3)

Lead Sponsor Collaborator
University Medical Center Groningen Juvenile Diabetes Research Foundation, Lexicon Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Finland,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary change from baseline in Urine Albumin-Creatinine Ratio (UACR) change from baseline in Urine Albumin-Creatinine Ratio (UACR) when treated with ambrisentan alone versus combination of sotagliflozin and ambrisentan. 4 weeks
Secondary change from baseline in mGFR Glomerular Filtration Rate (GFR) using iohexol clearance techniques. 4 weeks
Secondary Change in biomarkers of fluid retention Change from baseline biomarkers of fluid retention (body weight, hemoglobin, N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)) 4 weeks
Secondary Change in biomarkers of fluid retention Change from baseline biomarkers of fluid retention (Body Weight) 4 weeks
Secondary Change in biomarkers of fluid retention Change from baseline biomarkers of fluid retention (hemoglobin) 4 weeks
Secondary Change in biomarkers of fluid retention Change from baseline biomarkers of fluid retention (N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)) 4 weeks
Secondary Change from baseline Extracellular Volume (ECV) Extracellular volume (ECV) using iohexol clearance techniques and bioimpedance spectroscopy. 4 weeks
Secondary Change from baseline blood pressure Change in blood pressure as measure in mmHg 4 weeks
See also
  Status Clinical Trial Phase
Completed NCT02164279 - Validation of Biomarkers of Diabetic Nephropathy in Type I Diabetic Children
Completed NCT01521910 - Effect of Dietary Protein Restriction on Prognosis in Patients With Diabetic Nephropathy N/A