MSC for Occlusive Disease of the Kidney

Phase I Study of Autologous Mesenchymal Stem Cells in the Treatment of Atherosclerotic Renal Artery Stenosis

To determine the safety and toxicity of intra-arterial infused autologous adipose derived mesenchymal stromal (stem) cells in patients with vascular occlusive disease of the kidney.

Study Overview

• Status: Completed
• Conditions: Atherosclerotic Renal Artery Stenosis; Ischemic Nephropathy; Renovascular Hypertension
• Intervention / Treatment: Drug: Arterial infusion of autologous mesenchymal stem cells

Detailed Description

Individuals with unilateral arterial occlusive disease will be treated to injured kidney with autologous cells.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

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

4.1 Inclusion Criteria

1. Are between ages 40 and 80 years old.
2. Advanced vascular occlusive disease (atherosclerosis) affecting one or both kidneys: defined as a) loss of parenchymal volume and renal blood flow (measured by MDCT as previously described (17) and/or duplex ultrasound velocity above 300 cm/sec to the affected kidney to be infused with MSC's.
3. Have serum creatinine below 2.5 mg/dL
4. Have no-contraindications to angiography: severe contrast allergy
5. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
6. Ability to comply with protocol
7. Competent and able to provide written informed consent

4.2 Exclusion Criteria

1. Advanced CKD: Stage 5 (two kidney eGFR < 15 ml/min/1.73 m2) contralateral renal artery occlusion/stenosis above 75% or ESRD requiring dialysis
2. Clinically significant abnormalities on laboratory examination, including Bilirubin (> 2 x normal), platelets (<100 thousand), potassium (>5.5 mEq/L), and sodium (<130 mEq/L), ALT or AST more than 2 x normal, Prothrombin time (INR>1.4), Hemoglobin <10.0 g/dL.
3. Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure) that would, in the opinion of the investigators, compromise the safety of the patient.

4. Specific exclusions:

   1. Clinical history of deep vein thrombosis within three months of MSC administration
   2. Uncontrolled hypertension (Systolic BP >180 mmHg despite therapy)
   3. Active infection
   4. Reduced ejection fraction (below 30%)
   5. Evidence of hepatitis B,C, or HIV
   6. Diabetes treated with insulin and/or glucose lowering agents
   7. Anemia (Hgb<10 g/dL)
   8. Regular use of potentially renotoxic drugs, e.g. non-steroidal anti-inflammatory agents (NSAID's): (>2 x weekly)
5. History of cancer including melanoma (with the exception of localized skin cancers)
6. Investigational drug exposure within thirty (30) days of baseline
7. Beck's depression score above 16
8. Pregnant or breast feeding.
9. History of clinically significant auto-immunity or any previous example of fat-directed autoimmunity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: infusion of autologous mesenchymal stem cells; Patients will undergo a subcutaneous fat biopsy for expansion of mesenchymal stromal (stem) cells (MSC) in the Human Cell Therapy Laboratory. Patients will be admitted to the inpatient Clinical Research Unit of the Mayo Clinic Center for 3 days prior to treatment, for pre-infusion tests. Renal angiography will be performed to deliver a single intra-arterial dose of MSC's into one affected kidney. Patients will be observed for 24 hours for acute adverse events. Patients will have remote visits at 1 week, 4 weeks,8 weeks, and 6 months. At 3 months, patients will return for repeat evaluation of kidney function, blood flow and structural alterations within the clinical research unit at St. Mary's Hospital, Rochester, Minnesota. Thereafter, health assessment and blood draws will be repeated at 12 and 24 months with urinary cytology and MRI.

Drug: Arterial infusion of autologous mesenchymal stem cells; Other Names: MSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal blood flow and function in the treated kidneys.	Individual kidney blood flow, measured by multidetector CT contrast transit times, will be measured before and after MSC infusion.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of kidney function.	Level of kidney function will be assessed as glomerular filtration rate by iothalamate clearance. Tissue oxygenation within each kidney will be measured by Blood Oxygen Level Dependent (BOLD) magnetic resonance.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure levels.	Blood pressure will be assessed by oscillometric measurement.	2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Stephen Textor, MD, Mayo Clinic

Publications and helpful links

General Publications

• Camilleri ET, Gustafson MP, Dudakovic A, Riester SM, Garces CG, Paradise CR, Takai H, Karperien M, Cool S, Sampen HJ, Larson AN, Qu W, Smith J, Dietz AB, van Wijnen AJ. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production. Stem Cell Res Ther. 2016 Aug 11;7(1):107. doi: 10.1186/s13287-016-0370-8.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: April 23, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 25, 2013

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: chronic kidney disease; renal artery stenosis; renovascular hypertension; ischemic nephropathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Hypertension, Renal; Hypertension; Kidney Diseases; Constriction, Pathologic; Renal Artery Obstruction; Hypertension, Renovascular
• Other Study ID Numbers: 12-009298