Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

Chronic Kidney Disease Clinical Trial

Official title:

Hypoxia and Inflammatory Injury in Human Renovascular Hypertension : Phase 1 Trial of Mesenchymal Stem Cell Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02266394
• Other study ID #: 14-002799
• Status: Completed
• Phase: Phase 1
• Start date: October 21, 2014
• Est. completion date: September 25, 2020

Study information

• Verified date: January 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current treatments for ARAS based on restoring blood flow alone have been unsuccessful at recovering kidney function. For this reason we are studying a stem cell product called "mesenchymal stem cells" or MSC. Mesenchymal stem cells (MSC) are grown from a person's own fat tissue (obtained as a fat biopsy) and infused back into the patient's own kidney.

This study is also being done to determine if the MSC infusion prior to percutaneous transluminal renal angioplasty with stenting (PTRA) further enhances changes in single kidney blood flow and restoration of kidney function, as well as to assess the relationship between MSC dose and measures of kidney function.

Description:

These studies include participation by human subjects using a 3-day inpatient CRU protocol at St. Mary's Hospital. Studies include formal measurement of blood and urinary markers of kidney function, BOLD MR and multidetector CT scanning. Forty-two non-diabetic patients between 40 and 80 years of any race or ethnicity will be recruited. All will have hypertension (defined as BP≥140/90 mmHg or ongoing antihypertensive drug therapy) but will have less than 180 mmHg to be included (with or without drug therapy). These subjects will be free of cardiovascular events within 3 months and will not have implanted electrical devices, such as a pacemaker or defibrillator. All patients will have identified large vessel renovascular disease (RVD) for Aims 1, 2 and 3. At least 10% of these subjects will be of African-American descent (self-identified) and recruited in collaboration with the University of Mississippi under the direction of Dr. Luis Juncos and the University of Alabama under the direction of Dr. David Calhoun. For completion of Aims 2 and 3, a three-day evaluation will be repeated between three and four months later, and ongoing safety and imaging studies will be performed up to 24 months after MSC administration. Participants in these protocols will undergo transvenous kidney biopsy under the direction of Drs. McKusick and Misra and their colleagues in Interventional Radiology. All subjects for these studies will complete the research plan at Mayo Clinic, Rochester, Minnesota.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 25, 2020
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Creatinine <2.2 mg/dL for Caucasian males, <2.0 Caucasian females,< 2.4 African-American males, <2.1 mg/dL African-American females

• Hypertension (Systolic BP>155 mm Hg) and/or requirement for two or more antihypertensive medications: no restrictions on antihypertensive agents, although loop diuretics will be changed to diluting site agents (e.g. hydrochlorothiazide, indapamide, metolazone) prior to study.

• Angiotensin Converting Enzyme (ACE inhibitor) or Angiotensin Receptor Blocker (ARB) therapy maintained or initiated at usual recommended daily dose (equivalent: 40 mg lisinopril) .

Exclusion Criteria:

• Diabetes requiring insulin or oral hypoglycemic medications (see text)

• Known allergy to furosemide or iodinated intravenous contrast

• Pregnancy

• Recent Cardiovascular event: Myocardial infarction, stroke, congestive heart failure within 3 months

• Cardiac ejection fraction less than 30%

• Evidence of hepatitis B or C, or HIV infection

• requirement for potentially nephrotoxic drugs, e.g. non-steroidal anti-inflammatory drugs

• Uncontrolled hypertension: SBP >180 mm Hg, despite antihypertensive therapy

• Kidney transplant

• Pacemaker, implantable defibrillator or other contraindication to Magnetic resonance imaging

• Inability to comply with breath-hold for 30 seconds

• History of deep venous thrombosis within 3 months of enrollment

• contraindications to renal biopsy including artificial valve requiring continuous anticoagulation

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hypertension
• Hypertension, Renovascular
• Hypoxia
• Ischemic Nephropathy
• Kidney Diseases
• Renal Artery Obstruction
• Renal Artery Stenosis
• Renal Insufficiency, Chronic
• Renovascular Disease

Intervention

Drug:
• Mesenchymal stem cell
Intra-arterial infusion of the single-dose MSC

Procedure:
• Mesenchymal stem cell delivery with stent placement
Intra-arterial stent placement after Mesenchymal stem cell infusion

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	University of Mississippi	Jackson	Mississippi
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	University of Alabama at Birmingham, University of Mississippi Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Kidney function	Renal Tissue oxygenation	3 months
Primary	Safety of Mesenchymal stem cell infusion	Number of patients with tissue injury markers	2 years
Secondary	Decrease in Kidney inflammation	Venous and tissue biomarkers of inflammation	3 months

External Links

•   Mayo Clinic Clinical Trials