Clinical trial NCT05822609: Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes
Official title: Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Type 1 Diabetes
Keywords: Glucagon-like peptide-1 receptor agonist
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
name: University of Colorado, Denver
name: Providence Healthcare
name: University of Toronto
First posted: 2023-04-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the effects of semaglutide on kidney oxygenation and function in type 1 diabetes. The secondary objective is to determine the glycemic effects and safety of semaglutide in type 1 diabetes.

Detailed description: A parallel-group, double-blind, placebo-controlled, randomized study will rigorously test effects of semaglutide on the kidney. Real-time continuous glucose monitoring will be used to control glycemia during study run-in (prior to randomization) and during active therapy, which investigators anticipate will lead to similar glycemic control according to treatment assignment and ability to assess effects independent of glycemia. The trial duration is 26 weeks, a period of time sufficient to gradually titrate study medications to maximum target dose (over 12 weeks) and then observe the full short-term effect of semaglutide on the kidney.

Study Aims and Hypotheses:

Aim 1: Determine the effects of semaglutide vs. placebo on kidney oxygenation in type 1 diabetes. Hypothesis 1: Semaglutide will improve kidney oxygen availability in adults with type 1 diabetes.

Aim 2: Determine the effects of semaglutide vs. placebo on urine albumin-creatinine ratio and estimated glomerular filtration rate in type 1 diabetes. Hypothesis 2: Semaglutide will lower albuminuria and slow estimated glomerular filtration rate decline in adults with type 1 diabetes.

Aim 3: Determine the glycemic effects and safety of semaglutide vs. placebo in type 1 diabetes. Hypothesis 3: Semaglutide will reduce total daily insulin dose and improve glycemic variability without increasing risk of severe hypoglycemia or diabetic ketoacidosis in adults with type 1 diabetes.

Eligibility criteria: Inclusion Criteria:

* Adults (≥18 years) with type 1 diabetes
* Diabetes duration of ≥5 years
* Persistent urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g, on the most recent two measurements within the prior 3 years
* Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2
* Stable doses of drugs altering blood pressure (e.g., Angiotensin-converting enzyme inhibitor) required for at least 4 weeks prior to randomization, and requested for the duration of the trial
* Stable doses of lipid-lowering medications required for at least 4 weeks prior to randomization, and requested for the duration of the trial
* Adequate contraceptive method for females of child-bearing potential

Exclusion Criteria:

* HbA1c \>9%, recent diabetic ketoacidosis, hyperosmolar hyperglycemic state or severe illness requiring hospitalization in past 30 days
* Other causes of diabetes mellitus, including type 2 diabetes and maturity-onset diabetes of the young (MODY)
* Chronic kidney disease unrelated to diabetes
* Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) or thyroid nodule palpated by endocrinologist at screening
* Personal history of pancreatitis
* Current/planned pregnancy or nursing
* Uncontrolled thyroid disease or hypertension (Systolic blood pressure \[SBP\] ≥ 160 mm Hg or diastolic blood pressure \[DBP\] ≥ 100 mm Hg despite treatment)
* Proliferative retinopathy with treatment in the past 6 months
* Uncontrolled or potentially unstable diabetic retinopathy or maculopathy, verified by fundus examination with pupil dilation unless performed using a digital fundus photography camera specified for non-dilated examination
* More than 2 severe hypoglycemic episodes (requiring glucagon and/or assistance from another person) in the past 6 months
* Frequent hypoglycemia during the last two weeks of the study run-in phase (time below range \[\<70 mg/dL\] ≥4%)
* Pramlintide and the use of glycemia treatments not approved for type 1 diabetes by the FDA, e.g., metformin, SGT-2 inhibitor, GLP-1 receptor agonist, closed loop insulin delivery using unapproved algorithms
* Significant systemic conditions or treatment such as cancer or immunomodulators
* Known liver disease other than non-alcoholic fatty liver disease (NAFLD) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>100 IU/L, history of severe gastrointestinal disease (e.g., gastroparesis) or gallstones
* Body mass index \<20 kg/m2
* Inability to cooperate with or clinical contraindication for magnetic resonance imaging including severe claustrophobia, nonremovable devices, implanted metal
* Known or suspected allergy/sensitivity to semaglutide or its excipients
* Pregnant, breast feeding, or the intention of becoming pregnant
* The receipt of any investigational drug within 3 months prior to this trial
* Previously randomized in this trial

Primary outcomes:
measure: Change in kidney cortical relaxation rates (R2*)
timeFrame: Baseline to 26 weeks
Secondary outcomes:
measure: Change in urine albumin excretion
timeFrame: Baseline to 26 weeks
measure: Change in estimated glomerular filtration rate
timeFrame: Baseline to 26 weeks
measure: Change in glucose time in range
timeFrame: Baseline to 26 weeks
measure: Change in glucose coefficient of variation
timeFrame: Baseline to 26 weeks
measure: Change in total daily insulin dose
timeFrame: Baseline to 26 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
Study officials:
affiliation: University of Washington
name: Ian de Boer, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado Anschutz Medical Campus and Children's Hospital Colorado
name: Jessica Kendrick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto
name: David Cherney, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Irl Hirsch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Healthcare
name: Katherine Tuttle, MD
role: PRINCIPAL_INVESTIGATOR
References: