Feasibility Study of Non-Expanded Autologous Adipose Stromal Vascular Fraction Cells in DMARD-Resistant Rheumatoid Arthritis

Abstract

SVF cells are known to contain regenerative mesenchymal stem cells (MSC), as well as cells with immune modulatory/anti-inflammatory properties such as T regulatory cells and alternatively activated macrophages. Administration of these cells has been used in the Veterinay area and pre-clinic trials. However, up to date, no clinical trials or research has been conducted using a defined population of patients in a clinical scenario.

The proposed trial involves a lipoaspiration of 500 cc of adipose tissue from which cells will be harvested, SVF cells isolated, and reinfused on days 8 and 10. Patient observation will be performed for 52 weeks, with safety and efficacy measurements at 1, 2, 3 and 6 months. Cells will be administered intravenously as two infusions containing a minimum of 40 million cells per infusion. Patients whose yield is insufficient will be excluded from the trial. The trial protocol is based on experiences outside of the United States utilizing autologous SVF for autoimmune and inflammatory diseases and preliminary studies have been published by us [1, 2].

Given the historical use of autologous fat transplants as part of cosmetic surgery procedures and that SVF cells used in the current protocol do not require expansion, we do not anticipate treatment-related serious adverse events. This study will provide support for double-blind placebo controlled investigations. The potential of using a relatively benign procedure of liposuction as a biological treatment for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.

Inclusion Criteria

• Age >18 years and ability to understand the planned treatment.
• Patients of either gender with RA with a duration of 6 to 72 months defined as the presence of at 
least three of the following criteria: 6 or more painful or tender joints, three or more swollen joints, morning stiffness for at least 45 minutes (on average during the week prior to entry), and an erythrocyte sedimentation rate (ESR) of at least 28 mm.
• Nonresponsive to at least one course of one DMARD selected from a group comprising of: gold, leflunomide, methotrexate, and hydroxychlorquine.
• Second-line agents are discontinued at least 4 weeks prior to entry.
• Able to tolerate ALL study procedures
• Able to give informed Consent
• Negative for HcG with a serum pregnancy test
• Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000,
• Life expectancy of 6 months or more in the opinion of the investigator
• Serum bilirubin, ALT, AST £2.5 time the upper level of normal.
• Controlled blood pressure (systolic blood pressure ≤140 and a diastolic blood pressure of ≤90 
mmHG) and established anti-hypertensive therapy as necessary prior to entry into the study
• Patient has received stable, standard medical therapy for at least one month with no new 
medications to treat the disease introduced in the last month.
• Pre-existing condition (e.g. thromboembolic risk, diabetes, hypercholesterolemia are adequately 
controlled in the opinion of the investigator)
• Fertile patients (male and female) must agree to use an appropriate form of contraception while 
participating in the study.

Exclusion Criteria

• Female who is pregnant or nursing, or of child bearing potential and is not using a reliable birth control method, or who intend to become pregnant during the tenure of this study.
• History of prior radiation exposure for oncological treatment.
• History of Bone Marrow Disorder (especially NHL, MDS)
• History of abnormal bleeding or clotting.
• History of Liver Cirrhosis.
• End stage renal disease (Creatinine ≤ 3.0 mg / dl) and/or dialysis
• Active clinical infection being treated by antibiotics within one week of enrollment
• Inability or unwillingness to comply with the treatment protocol, follow-up, research tests, or give consent.
• History of life-threatening arrhythmias, except if an automated implantable cardioverter defibrillator (AICD) is implanted
• Life expectancy <6 months due to concomitant illnesses
• Patients receiving treatment with hematopoietic growth factors (e.g., EPO, G-CSF)
• Patients who can not stop anticoagulation therapy (warfarin) 72hrs prior to infusion
• Patients who can not stop anti-platelet therapy (clopidogrel) 7 days prior infusion
• Prior admission for substance abuse
• Body Mass Index (BMI) of 40 kg/m2 or greater
• Patient receiving experimental medication or participating in another clinical study within 30 days of signing the informed consent
• In the opinion of the investigator or the sponsor, the patient is unsuitable for cellular therapy

As seen on ClinicalTrials.gov

View this clinical trial on National Institutes of Health ClinicalTrials.gov

References

1. Ichim, T.E., et al., Autologous stromal vascular fraction cells: a tool for facilitating tolerance in rheumatic disease. Cellular immunology, 2010. 264(1): p. 7-17. 
2. Riordan, N.H., et al., Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. Journal of translational medicine, 2009. 7: p. 29.