Glucagon-Like Peptide-1 Receptor Agonist in ADPKD

NCT06582875 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 24-0594R01DK138915-01A1
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed clinical trial aims to assess if a year 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.

Conditions

Autosomal Dominant Polycystic Kidney; Obesity

Keywords

GLP1RA

Outcome Measures

Primary Outcomes (1)

• Change in height-Adjusted Total kidney volume

  To assess kidney growth,height-adjusted total kidney volume will be measured by magnetic resonance imaging at baseline and 12 months to determine annual percent change.

  Baseline, 12-months

Secondary Outcomes (15)

• Change in body weight

  Baseline, 12-months

• Change in abdominal adiposity

  Baseline, 12-months

• Change in adiponectin (circulating)

  Baseline, 6-months, 12-months

• Change in leptin (circulating)

  Baseline, 6-months, 12-months

• Change in interleukin-6 (circulating)

  Baseline, 6-months, 12-months

Other Outcomes (9)

• Change in renal blood flow

  Baseline, 12-months

• Safety (adverse events)

  12 months

• Adherence

  12 months

Study Arms (2)

Tirzepatide

EXPERIMENTAL

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

Other: Placebo

Interventions

Tirzepatide DRUG

Titrated to dose of 5 mg once weekly subcutaneous

Also known as: Zepbound

Tirzepatide

Placebo OTHER

Titrated to dose of 5 mg once weekly subcutaneous

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• ADPKD diagnosis based on the modified Pei-Ravine criteria
• Body-mass index of ≥27 kg/m\^2
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73m\^2
• Mayo Classification of C, D, or E, calculated from a previous kidney ultrasound or MRI performed within the last 12 months
• Not currently participating in or planning to participate in any formal weight loss or physical activity program, or another interventional study
• Ability to provide informed consent

You may not qualify if:

• Diabetes mellitus
• Tolvaptan usage or plans to initiate tolvaptan
• History of hospitalization or major surgery within the last 3 months
• Uncontrolled hypertension (systolic blood pressure \> 160 or diastolic blood pressure \>100 mm Hg)
• Pregnancy, lactation, or unwillingness to use adequate birth control
• Regular use of prescription or over-the-counter medications that may affect weight, appetite, food intake, or energy metabolism
• History of clinically diagnosed eating disorder including: anorexia nervosa, bulimia, binge eating disorder
• Weight change of \>5% in the past 3 months for any reason except post-partum weight loss
• Inability to cooperate with or clinical contraindication for MRI including: severe claustrophobia, implants, devices, or non-removable body piercings
• Presence or personal history of malignant neoplasm within 5 years prior to the day of screening
• Personal or family history of medullary thyroid carcinoma, thyroid nodule, or multiple endocrine neoplasia type 2
• Prior history of pancreatitis
• Weight ≥450 lb

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Washington University School of Medicine: collaborator
• Mayo Clinic: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (1)

• Cortinovis M, Perico N, Remuzzi G. The Need for Novel Therapeutic Directions in Autosomal Dominant Polycystic Kidney Disease Patient Care. Clin J Am Soc Nephrol. 2025 Dec 5. doi: 10.2215/CJN.0000000975. Online ahead of print.

  PMID: 41348481 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Kristen Nowak, PhD, MPH

CONTACT

3037244842; Kristen.Nowak@cuanschutz.edu

Diana George

CONTACT

303-724-1684; Diana.George@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: September 3, 2024
• Study Start: March 6, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

US (1)