Clinical trial NCT05154591: CKDu Treated With Intra-arterial Infusion of Autologous SVF Cells
Official title: Chronic Kidney Disease of Unknown Cause (CKDu) Treated With Directed Local Intra-arterial Infusion of Autologous Stromal Vascular Fraction (SVF) Cells.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Renal Failure of Unknown Cause
Keywords: Stromal vascular fraction
Mesenchynmal stem cells
Chronic kidney disease
Adipose stem cells
Lead sponsor: National Autonomous University of Nicaragua
Sponsor class: OTHER
Collaborators: name: Ministerio de Salud de Nicaragua
name: GID BIO
name: National Autonomous University of Nicaragua
First posted: 2021-12-13
Enrollment: 18
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an interventional study to treat 18 patients with chronic kidney disease of unknown cause (CKDu), formerly known as Mesoamerican nephropathy (MeN), with autologous adipose tissue-derived stromal vascular fraction (SVF) cells transplanted by intra-arterial injection both kidneys.

This study assesses: (1) safety and tolerability, (2) preliminary evidence of efficacy, (3) exploratory evidence of clinical effects.

Detailed description: Patients under go 24 hours of preoperative hydration combined with N-actyl cysteine 300 mg IV for prevention of nephrotoxicity. Under general anesthesia 200-300 cc of lipoaspirate is collected into a sterile processing cannister (GID SFV-1, Louisville, CO, USA). The tissue is washed and dissociated with collagenase (Worthington CLS-1, Lakewood, NJ, USA) at a concentration of 200 CDU/ml of total volume for 50 minutes at 39°C. This is followed by inactivation using 40 cc of human serum albumin. SVF cells are separated via centrifugation for 10 minutes at 800 g. The cell pellet is extracted and resuspended in Harmann solution with an aliquot (10 µl) removed for counting and viability assessment of resulting total nucleated cells (YNC) through and image cytometer (ADAM MC, Portsmouth NH, USA).

Femoral artery catheterization is performed permitting advancement of a 100 cc balloon-tip catheter into the renal artery under fluoroscopic control, with position confirmation using 1 cc of OrtoRay® 320 contrast diluted 1:4 with Hartmann solution. SVF cells are then admixed with 200 cc Hartmann solution warmed to 37°C and in fused using a DRE infusion pump (DRE Medical, Louisville, KY, USA) over a 15 minute period with constant agitation. On the 1st pos-operative day creatinine and glomerular filtration rate are checked and the patient is discharged.

Follow-up studies include clinical assessment, chemistries, and renal ultrasound to assess intra-parenchymal renal volume, renal blood flow distribution, and hilar artery vascular resistance.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Mesoamerican nephropathy
* Stages 3 and 4
* No other renal disease
* No essential hypertension

Exclusion Criteria:

* Significant abnormalities in laboratory tests that contraindicate surgical procedures.
* Acute pathology or complications of significant chronic pathologies in the 6 months prior to study entry, including, but not limited to:

Medical history of deep vein thrombosis Uncontrolled hypertension Active infection Reduced cardiac ejection fraction Hepatitis B, C or HIV Diabetes treated with insulin or glucose lowering agents Anemia (Hb \<9 g/dL) History of cancer Severe depression (Beck scale) Autoimmune disease

Primary outcomes:
measure: Incidence of treatment related adverse events
timeFrame: 36-months follow-up post intervention.
measure: Preliminary evidence of efficacy
timeFrame: Assessment of changes between day 7 and month 36 post intervention.
Secondary outcomes:
measure: Renal blood flow.
timeFrame: Up to month 12 post intervention.
measure: Kidney volume.
timeFrame: Up to month 12 post intervention.
measure: Renal arterial resistive index.
timeFrame: Up to month 12 post intervention.
Other outcomes:
Locations:
city: Leon
country: Nicaragua
facility: Hospital Escuela Oscar Danilo Rosales Arguello
Study officials:
affiliation: Wake Forrest Institute for Regenerative Medicine
name: Michael Carstens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Diego Correa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Sreedhar Mandayam, MD
role: STUDY_DIRECTOR
References:
citation: Brown JC, Shang H, Li Y, Yang N, Patel N, Katz AJ. Isolation of Adipose-Derived Stromal Vascular Fraction Cells Using a Novel Point-of-Care Device: Cell Characterization and Review of the Literature. Tissue Eng Part C Methods. 2017 Mar;23(3):125-135. doi: 10.1089/ten.TEC.2016.0377.
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citation: Carstens MH, Quintana FJ, Calderwood ST, Sevilla JP, Rios AB, Rivera CM, Calero DW, Zelaya ML, Garcia N, Bertram KA, Rigdon J, Dos-Anjos S, Correa D. Treatment of chronic diabetic foot ulcers with adipose-derived stromal vascular fraction cell injections: Safety and evidence of efficacy at 1 year. Stem Cells Transl Med. 2021 Aug;10(8):1138-1147. doi: 10.1002/sctm.20-0497. Epub 2021 Apr 7.
citation: Correa-Rotter R, Garcia-Trabanino R. Mesoamerican Nephropathy. Semin Nephrol. 2019 May;39(3):263-271. doi: 10.1016/j.semnephrol.2019.02.004.
citation: Guo J, Nguyen A, Banyard DA, Fadavi D, Toranto JD, Wirth GA, Paydar KZ, Evans GR, Widgerow AD. Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action. J Plast Reconstr Aesthet Surg. 2016 Feb;69(2):180-8. doi: 10.1016/j.bjps.2015.10.014. Epub 2015 Oct 24.
citation: Johnson RJ, Wesseling C, Newman LS. Chronic Kidney Disease of Unknown Cause in Agricultural Communities. N Engl J Med. 2019 May 9;380(19):1843-1852. doi: 10.1056/NEJMra1813869. No abstract available.
citation: Nguyen A, Guo J, Banyard DA, Fadavi D, Toranto JD, Wirth GA, Paydar KZ, Evans GR, Widgerow AD. Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature. J Plast Reconstr Aesthet Surg. 2016 Feb;69(2):170-9. doi: 10.1016/j.bjps.2015.10.015. Epub 2015 Oct 31.
citation: Wijkstrom J, Gonzalez-Quiroz M, Hernandez M, Trujillo Z, Hultenby K, Ring A, Soderberg M, Aragon A, Elinder CG, Wernerson A. Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy. Am J Kidney Dis. 2017 May;69(5):626-636. doi: 10.1053/j.ajkd.2016.10.036. Epub 2017 Jan 23.