Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

NCT ID: NCT02266394

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-21
• Study Completion Date: 2020-09-25

Brief 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.

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.

Conditions

Renal Artery Stenosis; Ischemic Nephropathy; Renovascular Disease; Chronic Kidney Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Mesenchymal stem cell

Intervention Type: DRUG

Intra-arterial infusion of the single-dose MSC

Mesenchymal stem cell delivery with stent placement

To test adjunctive delivery of MSC to individuals with advanced RVD undergoing renal artery stenting.

Group Type: ACTIVE_COMPARATOR

Mesenchymal stem cell

Intervention Type: DRUG

Intra-arterial infusion of the single-dose MSC

Mesenchymal stem cell delivery with stent placement

Intervention Type: PROCEDURE

Intra-arterial stent placement after Mesenchymal stem cell infusion

Interventions

Mesenchymal stem cell

Intra-arterial infusion of the single-dose MSC

Intervention Type: DRUG

Mesenchymal stem cell delivery with stent placement

Intra-arterial stent placement after Mesenchymal stem cell infusion

Intervention Type: PROCEDURE

Other Intervention Names

Mesenchymal stem cell delivery

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Mississippi Medical Center

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Stephen C. Textor, M.D.

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen C Textor, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

University of Alabama

Birmingham, Alabama, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi

Jackson, Mississippi, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34183258 (View on PubMed)

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

14-002799

Identifier Type: -

Identifier Source: org_study_id