Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Renal Artery Stenosis; Ischemic Nephropathy; Renovascular Disease
• Intervention / Treatment: Drug: Mesenchymal stem cell; Procedure: Mesenchymal stem cell delivery with stent placement

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mesenchymal stem cell delivery; To determine hemodynamic and immunologic changes associated with intra-renal delivery of adipose-derived MSC into human subjects with advanced RVD.	Drug: Mesenchymal stem cell; Intra-arterial infusion of the single-dose MSC; Other Names: Mesenchymal stem cell delivery
Active Comparator: Mesenchymal stem cell delivery with stent placement; To test adjunctive delivery of MSC to individuals with advanced RVD undergoing renal artery stenting.	Drug: Mesenchymal stem cell; Intra-arterial infusion of the single-dose MSC; Other Names: Mesenchymal stem cell delivery; Procedure: Mesenchymal stem cell delivery with stent placement; Intra-arterial stent placement after Mesenchymal stem cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kidney function	Renal Tissue oxygenation	3 months
Safety of Mesenchymal stem cell infusion	Number of patients with tissue injury markers	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Kidney inflammation	Venous and tissue biomarkers of inflammation	3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: University of Alabama at Birmingham; University of Mississippi Medical Center
• Investigators: Principal Investigator: Stephen C Textor, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Lerman LO. Cell-based regenerative medicine for renovascular disease. Trends Mol Med. 2021 Sep;27(9):882-894. doi: 10.1016/j.molmed.2021.06.004. Epub 2021 Jun 25.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2014
• Primary Completion (Actual): September 25, 2020
• Study Completion (Actual): September 25, 2020

Study Registration Dates

• First Submitted: September 18, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Urologic Diseases; Renal Insufficiency; Signs and Symptoms, Respiratory; Hypertension, Renal; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Renal Artery Obstruction; Hypoxia; Hypertension, Renovascular
• Other Study ID Numbers: 14-002799

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO