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Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

Primary Purpose

Renal Artery Stenosis, Ischemic Nephropathy, Renovascular Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Mesenchymal stem cell

Mesenchymal stem cell delivery with stent placement

About this trial

This is an interventional treatment trial for Renal Artery Stenosis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Alabama
Mayo Clinic
University of Mississippi

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Mesenchymal stem cell delivery

Mesenchymal stem cell delivery with stent placement

Arm Description

To determine hemodynamic and immunologic changes associated with intra-renal delivery of adipose-derived MSC into human subjects with advanced RVD.

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

Outcomes

Primary Outcome Measures

Change in Kidney function

Renal Tissue oxygenation

Safety of Mesenchymal stem cell infusion

Number of patients with tissue injury markers

Secondary Outcome Measures

Decrease in Kidney inflammation

Venous and tissue biomarkers of inflammation

Full Information

NCT ID

NCT02266394

First Posted

September 18, 2014

Last Updated

January 25, 2021

Sponsor

Mayo Clinic

Collaborators

University of Mississippi Medical Center, University of Alabama at Birmingham

1. Study Identification

Unique Protocol Identification Number

NCT02266394

Brief Title

Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

October 21, 2014 (Actual)

Primary Completion Date

September 25, 2020 (Actual)

Study Completion Date

September 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

Collaborators

University of Mississippi Medical Center, University of Alabama at Birmingham

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mesenchymal stem cell delivery

Arm Type

Active Comparator

Arm Description

To determine hemodynamic and immunologic changes associated with intra-renal delivery of adipose-derived MSC into human subjects with advanced RVD.

Arm Title

Mesenchymal stem cell delivery with stent placement

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Mesenchymal stem cell

Other Intervention Name(s)

Mesenchymal stem cell delivery

Intervention Description

Intra-arterial infusion of the single-dose MSC

Intervention Type

Procedure

Intervention Name(s)

Mesenchymal stem cell delivery with stent placement

Intervention Description

Intra-arterial stent placement after Mesenchymal stem cell infusion

Primary Outcome Measure Information:

Title

Change in Kidney function

Description

Renal Tissue oxygenation

Time Frame

3 months

Title

Safety of Mesenchymal stem cell infusion

Description

Number of patients with tissue injury markers

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Decrease in Kidney inflammation

Description

Venous and tissue biomarkers of inflammation

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen C Textor, M.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55902

Country

United States

Facility Name

University of Mississippi

City

Jackson

State/Province

Mississippi

ZIP/Postal Code

39216

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34183258

Citation

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.

Results Reference

derived

Links:

URL

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

Description

Mayo Clinic Clinical Trials

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Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

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