ATHENA Clinical Trial Shows that Fat-Based Stem Cell Mixture Improves Heart Patient’s Health, But Does Not Improve Ejection Fraction.

The ATHENA trial is a clinical trial designed to test the ability of a patient’s own “adipose-derived regenerative cells” or ADRCs to improve to improve their heart function. In this trial, heart disease patients received injections of their own ADRCs into their heart muscle. Then these patients were followed and their symptoms, rates of hospitalizations, and heart function were monitored over a period of several months. The initial plans were to examine each patient at one week and at one, three, six, and twelve months after the procedure, and to interview patients via telephone calls from study staff two, three, four, and five years after the procedure.

The ATHENA trial results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions in Orlando, Fla.

ADRCs are isolated from fat that is collected by means of liposuction. The processing procedure uses a Celution®System (Cytori Therapeutics, San Diego, CA) cell processing unit to separate the mature fat cells and red blood cells (and other unwanted material, i.e., connective tissue and so on) from the other cells. The processed material, or ADRC fraction is an admittedly mixed population of cells that includes some mesenchymal stem cells (a type of adult stem cell), endothelial progenitor cells, leukocytes (white blood cells), endothelial cells (which compose the inner lining of blood vessels), and vascular smooth muscle cells. Several studies in laboratory animals have shown that ADRCs can promote healing of scarred or injured tissue, but the precise exact mechanisms by which ADRCs do this is uncertain. Pre-clinical studies have shown that ADRCs can quell inflammation, stimulate new blood vessel formation, promote cell survival and prevent cell death, and secrete molecules that promote tissue repair and regeneration.

The key advantage of ADRCs come from the fact that fat is the richest source of adult stem and regenerative cells. For example, one gram of fat contains approximately 5,000 stem cells and these cells can be collected and processed in the same day.

The results of the ATHENA trial to data showed that the heart muscle of those who had received injections of their own ADRCs demonstrated symptomatic improvement and a trend towards lower rates of heart failure hospitalizations and angina (chest pain). However, there was no significant improvement in left ventricle ejection fraction (LVEF) or ventricular volumes.

“ADRCs consist of multiple cell types with multiple potential benefits,” said Timothy D. Henry, MD, MSCAI, director, division of cardiology at the Cedars-Sinai Heart Institute and the study’s lead investigator. “Based on the results seen with ADRCs in the PRECISE trial, we designed ATHENA to look at these cells as a possible treatment option for people with refractory chronic myocardial ischemia.”

This phase 2 program consisted of two prospective, randomized double-blind, placebo-controlled, parallel group trials that were called ATHENA and ATHENA II. The patients in this study had an average age of 65 years in both groups. 17 patients received injections of their own ADRCs into their heart muscle and 14 received the placebo. The ejection factions of these patients (the percentage of blood pumped out of the ventricles with each contraction) were between 20-45 percent (normal is around high 40s to low 50s). The ejection fraction or EF can be an early indicator of heart failure if it is 35 percent or below, and the baseline average EF score for both groups was 31.6 percent. The patients were also suffered from angina pectoris, a chest pain that occurs when the heart receives too little oxygen. All patients had blocked coronary arteries but were not candidates for revascularization therapies.

One year after receiving the therapy, the ADRC-treated patients registered improvement in their heart failure classification (57 percent) and angina classification (67 percent) relative to the placebo group (15 percent and 27 percent, respectively). Further, when evaluated with the Minnesota Living with Heart Failure questionnaire, the ADRC-treated patients showed distinct improvements over those who had received the placebo (-21.6 vs. -5.5, p=0.038), and displayed a trend toward fewer heart failure hospitalizations (centrally adjudicated [2/17, 11.7 percent vs. 2/14, 21.4 percent]). However, to emphasize again, there were no between group differences in LVEF or ventricular volume.

The ATHENA trial only examined a small patient population, but the results are potentially promising and consistent with what was seen with PRECISE and might provide the foundation for a large phase 3 trial.

The study, designed to enroll 90 patients, was terminated prematurely due to three neurological events that prolonged trial enrollment, but were not cell related.

The fact that patients feel better and do better with the ADRC treatment is encouraging, but without showing improved objective measures in heart physiology, such as increased ejection fraction, decreased end-diastolic volume and end-systolic volume, such a treatment will have a hard time finding enthusiastic endorsement among cardiologists.