Feasibility of Study of Empagliflozin in Patients With Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT05510115

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-18
• Study Completion Date: 2026-03-31

Brief Summary

The investigator proposes a pilot randomized clinical trial to determine the safety and tolerability of empagliflozin in ADPKD patients. To achieve this, the investigator will conduct a 12-month parallel-group, randomized, double-blind, placebo-controlled trial in 50 ADPKD patients with an eGFR 30-90 mL/min/1.73m2.

Detailed Description

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by development and continued growth of numerous fluid-filled kidney cysts that result in ultimate loss of kidney function in the majority of individuals. ADPKD manifestations are not limited to the kidney. It is well established that arterial stiffness, an important predictor of future cardiovascular events and mortality, is present early in the course of ADPKD. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) have a track record of tolerability and safety in patients with diabetic and non-diabetic kidney disease. Studies of SGLT2i have been extremely encouraging and the expectation is that these treatments will become standard of care for diabetic and non-diabetic kidney disease; however, the mechanism of action is not fully understood and seems non-specific with regards to disease etiology. The potential benefit of SGLT2i has not been examined in ADPKD, as major trials of SGLT2i in non-diabetic chronic kidney disease (CKD) have excluded patients with ADPKD. It is also important to note the potential benefits of SGLT2i outside of delaying loss of kidney function, as these class of drugs have been shown to provide a mortality benefit for patients across the CKD spectrum. Thus, novel interventions to slow kidney disease progression and reduce vascular morbidity within ADPKD population are of clinical importance.

Limited data suggests SGLT2i may stimulate vasopressin and vasopressin receptor expression by causing glucosuria, natriuresis, and glucose osmotic diuresis, at least in patients and animal models without ADPKD. Vasopressin is known to stimulate cyst growth in ADPKD and promote disease progression. SGLT2i have been studied in animal models of ADPKD, with conflicting data. Some studies in rodent ADPKD models treated with SGLT2i failed to show a significant reduction in cyst growth. However, because of SGLT2i's beneficial effects on kidney function, vascular function, and mortality in non-ADPKD patients with CKD, further investigations of SGLT2i in patients with ADPKD are needed.

Primary Outcome Measure (Aim1): Safety will be assessed by laboratory testing and recording of adverse events. Tolerability will be assessed by subject drop-out rate due to adverse events and the proportion tolerating the maximal dose of study drug. Adherence to the intervention will be assessed by counting the returned number of tablets during check-in visits. Subjects will have check-in visits every 2 weeks the 1st month, monthly on month 2 and 3 and then every 3 months until the end of the study. Subjects will discuss issues with tolerability or treatment-emergent adverse events with a member of the clinical staff who is blinded to treatment status.

Secondary (Exploratory) Outcome Measures (Aim 2): (a) Height-adjusted total kidney volume will be examined by magnetic resonance imaging, at baseline, 3 months and 12 months after treatment with empagliflozin or placebo; (b) Aortic stiffness will be evaluated as aortic pulse wave velocity, at baseline, 3 months and 12 months after treatment with empagliflozin or placebo; (c) Plasma copeptin levels and urinary kidney injury molecule-1 will be measured at baseline, 3 months and 12 months after treatment with empagliflozin or placebo; and (d) Patient related outcomes will be measured using the ADPKD Impact Scale (ADPKD-IS) at baseline, 3 months and 12 months after treatment with empagliflozin or placebo.

Conditions

Polycystic Kidney, Autosomal Dominant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental

Empagliflozin

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

Empagliflozin: The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-\[4-chloro-3-\[\[4-\[\[(3S)-tetrahydro-3furanyl\]oxy\]phenyl\]methyl\]phenyl\]-, (1S). Empagliflozin is a white to yellowish, non-hygroscopic powder. It is very slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol and acetonitrile; soluble in 50% acetonitrile/water; and practically insoluble in toluene. Empagliflozin power will be added in white and bovine origin gelatin capsules. Each capsule of empagliflozin will contain 10 mg or 25 mg of empagliflozin (free base) and the following inactive ingredients: microcrystalline cellulose magnesium, stearate, dicalcium phosphate, and silicone dioxide.

Placebo comparator

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules will be matched in size and color to empagliflozin capsules. Each placebo capsule will contain the following inactive ingredients: microcrystalline cellulose magnesium, stearate, dicalcium phosphate, and silicone dioxide.

Interventions

Empagliflozin

Empagliflozin: The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-\[4-chloro-3-\[\[4-\[\[(3S)-tetrahydro-3furanyl\]oxy\]phenyl\]methyl\]phenyl\]-, (1S). Empagliflozin is a white to yellowish, non-hygroscopic powder. It is very slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol and acetonitrile; soluble in 50% acetonitrile/water; and practically insoluble in toluene. Empagliflozin power will be added in white and bovine origin gelatin capsules. Each capsule of empagliflozin will contain 10 mg or 25 mg of empagliflozin (free base) and the following inactive ingredients: microcrystalline cellulose magnesium, stearate, dicalcium phosphate, and silicone dioxide.

Intervention Type: DRUG

Placebo

Placebo capsules will be matched in size and color to empagliflozin capsules. Each placebo capsule will contain the following inactive ingredients: microcrystalline cellulose magnesium, stearate, dicalcium phosphate, and silicone dioxide.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Autosomal Dominant Polycystic Kidney Disease (ADPKD) as defined by modified Pei-Ravine Criteria;
• Age 18-55 yrs;
• Estimated Glomerular Filtration Rate (eGFR) 30-90 ml/min/1.73m2;
• Mayo imaging-based risk classification 1C, 1D, or 1E;
• Stable renal function over prior 3 months.

Exclusion Criteria

• Known diabetes mellitus;
• Fasting Glucose >120 mg/dL;
• HbA1C≥6.5%;
• Seated systolic blood pressure <100 mm Hg;
• Seated systolic blood pressure >160 mm Hg;
• Known heart failure with reduced ejection fraction (HFrEF);
• Current use of loop diuretic;
• Current use of tolvaptan or other V2 receptor antagonist;
• Current urinary tract or urogenital infection;
• Pregnant or lactating;
• Vascular claudication, lower extremity skin infection or ulcers;
• Contraindication to magnetic resonance imaging (e.g., severe claustrophobia, implanted ferromagnetic device).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel B Chonchol, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Coloardo Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

References

Eswarappa M, Madden E, Shlipak MG, Cui X, Mrug M, Estrella MM, Park M. Sodium-Glucose Cotransporter-2 Inhibitor Therapy and Longitudinal Changes in Kidney Function among Veterans with Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol. 2025 May 16;20(7):940-949. doi: 10.2215/CJN.0000000725.

Reference Type: DERIVED

PMID: 40377984 (View on PubMed)

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Hogan MC, Simmons K, Ullman L Jr, Gondal M, Dahl NK. Beyond Loss of Kidney Function: Patient Care in Autosomal Dominant Polycystic Kidney Disease. Kidney360. 2023 Dec 1;4(12):1806-1815. doi: 10.34067/KID.0000000000000296. Epub 2023 Nov 27.

Reference Type: DERIVED

PMID: 38010035 (View on PubMed)

Other Identifiers

1R01DK131755-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-0616

Identifier Type: -

Identifier Source: org_study_id