A Modified Study Design for Blinded Randomized Controlled Trial in Orthobiologic Therapy

Abstract

Background: The utility of cellular based therapeutic agents in management of various ailments and conditions is promising, particularly in the field of orthopedics. However, an evidence-based medicine approach must be implemented to validate these novel cellular based therapies before they can be translated into routine clinical practice. Given pain relief is a primary goal of novel treatments for orthopedic disease, future orthobiologic clinical trials will need to overcome challenges such as the placebo effect or the placebo response and difficult participant recruitment. In this paper, we describe a clinical study that evaluates the safety and efficacy of autologous stromal vascular fraction (SVF) cells that adheres to a patient blinded, randomized and placebo-controlled study design while still offering the patient the opportunity to participate in the therapeutic intervention by using cell preservation techniques. Methods: This pilot clinical trial studies the safety and feasibility of intra-articular transplantation of SVF cells in patients with knee osteoarthritis with secondary outcomes of improving pain relief. The RCT aims to recruit 30 patients. Liposuction is performed on each patient to isolate SVF cells. 15 subjects are randomized to receive SVF injection in the same surgical procedure and 15 subjects receive placebo injection directly into their affected knee joint. The placebo group’s SVF cells are then frozen and preserved. At the 6-month follow-up visit, those who received the placebo are unblinded and have the option to receive the SVF injection as a condition for participation in the trial. Feasibility of liposuction, SVF manufacturing, cell preservation/thaw techniques and adverse outcomes are all primarily tracked. Secondary outcomes include standardized patient reported outcomes score responses to the treatments. Discussion: The design of this pilot study offers study subjects the opportunity to receive a novel therapeutic intervention even within a placebo arm and enables the investigators to blind subjects without performing an unnecessary liposuction or discarding the resulting cellular product which could encourage hesitant individuals to participate in the trial. This may aid in overcoming the challenges associated with recruiting participants for cell therapy trials concerned with being randomized to a control arm. The results of this trial will help to assess both the safety and feasibility of SVF injections to treat knee osteoarthritis as well as help plan larger phase controlled trials. However, precautionary measures are necessary to ensure the safety and well-being of patients receiving cell-based therapy. Proper handling and storage of the cellular product must be considered and are demonstrated here. Trial Registration ClinicalTrials.gov Identifier: NCT03940950