Clinical trial NCT02266394: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Artery Stenosis
Ischemic Nephropathy
Renovascular Disease
Chronic Kidney Disease
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of Mississippi Medical Center
name: University of Alabama at Birmingham
First posted: 2014-10-17
Enrollment: 42
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Kidney function
timeFrame: 3 months
measure: Safety of Mesenchymal stem cell infusion
timeFrame: 2 years
Secondary outcomes:
measure: Decrease in Kidney inflammation
timeFrame: 3 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
Study officials:
affiliation: Mayo Clinic
name: Stephen C Textor, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.