Glucagon-Like Peptide-1 Receptor Agonist in ADPKD
NCT Number: NCT06582875
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Autosomal Dominant Polycystic Kidney|Obesity
Sponsor: University of Colorado, Denver
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 126
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-12-01
Completion Date: 2029-06-30

Summary:
The proposed clinical trial aims to assess if two years of treatment with a glucagon-like peptide 1 receptor agonist, a medication approved for weight management that also improves the body's response to glucose and insulin, can slow kidney growth in adults with autosomal dominant polycystic kidney disease who are overweight or obese. The study will also evaluate changes in abdominal fat and kidney metabolism using cutting-edge images techniques. Blood and urine samples will provide further insight into biological changes that may be linked to the benefits of the intervention, while ensuring careful monitoring of safety and tolerability.

Primary Outcome Measures: Change in height-Adjusted Total kidney volume, To assess kidney growth, we will measure height-adjusted total kidney volume by magnetic resonance imaging at baseline and 24 months to determine annual percent change., Baseline, 24-months
Secondary Outcome Measures: Change in body weight, Change in body weight over the 24-month period will be measured using a calibrated digital scale., Baseline, 24-months|Change in abdominal adiposity, Abdominal adiposity (subcutaneous, visceral, and total) will be assessed by magnetic resonance imaging., Baseline, 24-months|Change in adiponectin (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in leptin (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in interleukin-6 (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in tumor necrosis-factor-alpha (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in high-sensitivity C-reactive protein (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in 8-isoprostane (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in copeptin (circulating), Venous blood samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in HOMA-IR, The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) will use fasting glucose and insulin to calcuate insulin sensitivity, Baseline, 6-months, 12-months, 24-months|Change in HOMA-β, The Homeostatic Model Assessment of β-cell function (HOMA-β) will use fasting glucose and insulin to calcuate insulin secretion., Baseline, 6-months, 12-months, 24-months|Change in 8-isoprostane (urinary), Sport urine samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in copeptin (urinary), Sport urine samples will be analyzed for this mechanistic biomarker, Baseline, 6-months, 12-months, 24-months|Change in renal oxygen consumption, Renal oxygen consumption will be assessed by a PET/CT scan using 11-C acetate in a sub-set of participants, Baseline, 24-months|Change in gut microbiota, 16S rRNA gene sequencing will be used for taxonomic characterization of the gut microbiota in a subset of participants., Baseline, 24-months
Other Outcome Measures: Change in renal blood flow, Phase contrast magentic resonance imaging will be used to measure change in renal blood flow, Baseline, 24-months|Safety (adverse events), Number of participants with treatment-related adverse events in each group as evaluated by the DSMB, 24 months|Adherence, Compliance will be assessed by cross-checking the following sources and comparing these to the expected use: (1) drug accountability information; (2) counting returned trial product, visual inspection of pens; and (3) discussion with participants., 24 months|Tolerability (dropout due to adverse events), Subject dropout due to treatment-emergent adverse events, 24 months|Kidney Function Decline, Estimated glomerular filtration rate trajectories will be compared between the semaglutide and placebo group as an exploratory endpoint to inform a subsequent phase III trial., Baseline, 1 month, 3 months, 6-months, 12-months, 24-months|Change in dietary energy Intake, Multiple pass 24-hr dietary recalls will be analyzed to evaluate self-reported energy intake, Baseline, 1 month, 6-months, 12-months, 24-months|Change in free-living physical activity, Estimated energy expenditure (METs) over a 7-day period will be quantified using the ActiGraph wGT3X-BT activity monitor, Baseline, 12-months, 24 months|Change in resting energy experniture, Resting energy expenditure will be assessed using indirect calorimetry., Baseline, 24 months|Change in percent body fat, Percent body fat will be assessed via DEXA scan in a sub-set of participants., Baseline, 24 months