Statin Therapy in Patients With Early Stage ADPKD

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03273413
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 64
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This study plans to learn if pravastatin is helpful in slowing down the progression of kidney disease in adults with autosomal dominant polycystic kidney disease (ADPKD). Pravastatin has been approved by the Food and Drug Administration (FDA) for adults for treatment of hyperlipidemia (high cholesterol levels). The investigators are using pravastatin in this study as an investigational drug for treatment of ADPKD.

Condition or Disease	Intervention/Treatment	Phase
ADPKD; Autosomal Dominant Polycystic Kidney	Drug: Pravastatin; Drug: Placebo	Phase 4

Detailed Description

This is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy and benefits of pravastatin therapy in adults with ADPKD by evaluating 1) kidney volume as measured by kidney magnetic resonance imaging (MRI); 2) renal blood flow as measured by kidney magnetic resonance angiography (MRA); 3) kidney function as assessed by Glofil-125; 4) plasma and urine protein markers that will allow a better understanding of how pravastatin works in ADPKD; and 5) blood vessel stiffness as measured by carotid-femoral pulse wave velocity. These parameters will be measured at baseline and after 2 years of pravastatin or placebo treatment in 150 patients with ADPKD.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, parallel study design.Randomized, double-blind, placebo-controlled, parallel study design.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Statin Therapy in Patients With Early Stage ADPKD
• Actual Study Start Date: Aug 31, 2017
• Anticipated Primary Completion Date: Jan 1, 2023
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will receive inactive 40 mg tablets of placebo everyday for 6 weeks. If well tolerated, participants will continue taking inactive 40 mg dose of placebo everyday for 2 years.	Drug: Placebo; Inactive tablet
Active Comparator: Pravastatin Participants will receive 40 mg tablets of pravastatin everyday for 6 weeks. If well tolerated, participants will continue taking 40 mg dose of pravastatin everyday for 2 years.	Drug: Pravastatin; Anti-inflammatory, anti-oxidative stress, and anti-proliferative therapy

Outcome Measures

Primary Outcome Measures

1. Change in Total Kidney Volume [Baseline, 2 years]

   Total kidney volume as assessed by renal MRI, at baseline and after 2 years of treatment

Secondary Outcome Measures

1. Change in Renal Blood Flow [Baseline, 2 years]

   Renal blood flow, as assessed by renal MRA, at baseline and after 2 years of treatment

2. Change in Kidney Function [Baseline, 2 years]

   Glomerular filtration rate (GFR), as assessed by Glofil-125, at baseline and after 2 years of treatment

3. Change in Circulating Inflammatory Markers [Baseline, 2 years]

   Plasma levels of inflammatory cytokines and growth factors at baseline and after 2 years of treatment

4. Change in Circulating Markers of Oxidative Stress [Baseline, 2 years]

   Plasma levels of oxidative stress markers at baseline and after 2 years of treatment

5. Change in Urinary Epithelial Cells [Baseline, 2 years]

   Urinary epithelial cell protein expression, as assessed by immunofluorescence, at baseline and after 2 years of treatment

Other Outcome Measures

1. Change in Blood Vessel Stiffness [Baseline, 2 years]

   Blood vessel stiffness, as assessed by carotid-femoral pulse wave velocity, at baseline and after 2 years

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of ADPKD

• Total kidney volume >500 mL

• Estimated glomerular filtration rate (GFR) ≥60 mL/min/1.73m^2

• Controlled blood pressure <140/80 mmHg

Exclusion Criteria:

• Uncontrolled hypertension

• Diabetes mellitus

• Renal disease, renal cancer, single kidney, recent renal surgery, or acute kidney injury

• Unstable angina

• Coronary artery disease

• Prior ischemic stroke

• Other clinical indication for a statin

• History of hospitalizations within the last 3 months

• Hepatic impairment or liver function abnormalities

• Secondary hypercholesterolemia or hypocholesterolemia

• Use of tolvaptan, gemfibrozil, other fibrates, niacin, clarithromycin, or cyclosporine

• Hypersensitivity to statins

• Immunosuppressive therapy within the last year

• Clinical contraindication for an MRI (i.e. implants, pacemaker, claustrophobia)

• Hypersensitivity to iodine

• Pregnant or breast feeding

• Current tobacco use

• Alcohol abuse or dependence

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver Anschutz Medical Campus	Denver	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Michel Chonchol, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, Schrier RW. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014 May;9(5):889-96. doi: 10.2215/CJN.08350813. Epub 2014 Apr 10.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03273413
• Other Study ID Numbers: 17-0678
• First Posted: Sep 6, 2017
• Last Update Posted: Jan 11, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of Colorado, Denver: Pravastatin; Statin
• Additional relevant MeSH terms: Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Pravastatin

Study Results

No Results Posted as of Jan 11, 2022