Redefining Evaluation of Adiposity and Leanness: Broadening Objective Diagnostics for Obesity

Redefining Evaluation of Adiposity and Leanness: Broadening Objective Diagnostics for Obesity (REAL-BODY)

The purpose of this study is to evaluate body composition across a variety of medical, professional, and commercial devices, including: bioelectrical impedance analysis (BIA) devices, 3-dimensional optical imaging (3DO), manual anthropometry measurements, dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and blood tests. The secondary study purpose is to compare body composition measurements from BIA devices, 3DO, and manual anthropometry measurements within a 1-week period for a subset of the study population.

The study plans to enroll 300 healthy (having no life-threatening conditions or diseases; male and female) participants, 18 years of age or older.

Obesity is a disease of excess and abnormal distribution of adipose tissue. Even though negative metabolic outcomes of obesity are driven by adipose tissue, investigators still use body weight (comprised of both fat and fat-free mass) in the calculation of body mass index (weight in kg divided by height in meters squared) to define, subclassify and monitor treatment in people with obesity. Despite this traditional focus on body weight, body composition is an important consideration in the management of people with obesity.

Clinical trials and clinical research often use DXA and MRI to quantify changes in body composition; however these methods are expensive and not easily implemented. It is desirable to monitor fat mass and other body composition outcomes in individuals with obesity taking weight loss medications as well as when new weight management therapeutic drugs are developed.

Most weight loss medications are associated with loss of both fat mass and fat-free mass with the "quality of weight loss" defined as the proportion of weight lost as fat mass, equal to 60-75%. Recognizing that loss of fat-free mass during weight loss is undesirable, several companies are developing lean mass preserving weight loss agents. For these agents, stepping on a weight scale will no longer be an accurate measure of benefit; loss in fat is offset by gains in lean, rendering body weight changes as an inaccurate measure of weight loss quality. Therefore, the application of body composition measurements will be required for patients, physicians, and payors to monitor treatment in people with obesity. In order for this to occur, investigators need scalable body composition measurements for fat mass.

Bioelectrical impedance analysis (BIA) offers a more scalable approach as the time, cost and footprint of BIA devices make them appropriate for a physician's office and for clinical research trials. Traditionally, BIA devices have been deemed to possess insufficient accuracy for body composition quantification. While this decreased accuracy was an obstacle for first generation weight loss medications with less weight loss, it is possible that with the newer generation of weight loss medications that confer greater weight loss, BIA may be adequate to measure changes in body composition occurring over time in individuals losing weight. Additionally, notable technological innovation has occurred in the field of bioimpedance, with several new devices possessing improved hardware and software as compared to previously evaluated analyzers. As such, these devices are expected to outperform traditional BIA systems.

Other accessible technologies that are practical to apply in clinical research and practice have appeared in recent publications. These include three-dimensional optical systems (3DO) housed in smartphones and multi-omics blood tests capable of estimating various body compartments. To the extent that BIA and these newer technologies can serve as useful sufficiently reproducible phenotypic measures of a person's body composition remains largely unknown. In addition to the dichotomy of fat mass vs fat-free mass, not all fat mass is created equal. Superficial or subcutaneous fat mass is thought to be metabolically healthy whereas visceral central fat is thought to be metabolically unhealthy. Furthermore, visceral fat is associated with long-term morbidity and mortality. Therefore, another dimension of body composition is the proportion of fat in the visceral vs subcutaneous compartments.

Currently, MRI is the gold standard method to measure visceral fat. Some BIA analyzers provide estimations of visceral fat, and digital anthropometry derived from 3D scanning can also be used in visceral fat estimation equations. As such, an additional goal of this project is to determine if visceral fat can be accurately estimated in the real-world using BIA or 3DO. Currently there are two major manufacturers of DXA devices, Hologic and General Electric (GE). Accuracy and precision data for body composition measures using DXA have been published. For BIA, there are several different manufacturers including InBody, Tanita, Seca, and Impedimed. Likewise, several companies produce 3DO smartphone systems, and one company provides multi omics blood evaluations for body composition. It is not known which of these devices and measurement platforms (if any) have adequate accuracy to measure body composition. The overall goal of this project is to bring measurement of body composition to the real world to improve the diagnosis, classification, and monitoring of treatment in people with obesity, both in clinical research trials and medical practice. Adipose or fat mass needs to become a new "vital sign." This project could have a large impact on the treatment of people with obesity. Accurate implementation of body composition analysis in the real world could lead to the development of treatment goals for obesity based on either total fat mass and/or visceral fat mass.

Inclusion Criteria:

• Being willing to provide written informed consent prior to participation Being willing to complete the study visits and comply with the study procedures
• Being willing to travel to the various study locations for On-site, DXA, MRI, and Phlebotomy visits
• Being willing to change into appropriate form-fitting clothing for 3DO assessments and/or appropriate gowns for DXA and MRI imaging
• Must have a BMI within the range of 18.5 - 45 kg/m2
• Being willing to refrain from all food, drink, and substances for 8 hours prior to the On-site visit(s) and phlebotomy visit
• Being willing to refrain from all food, drink, and substances for 4 hours prior to the DXA and MRI scan visits
• Being willing to refrain from any exercise or vigorous physical activity for 24 hours prior to all visits
• Stable weight (no more than 5 kg change) for 3 months prior to screening
• If recruited in the Phoenix, AZ area, participants must be willing to drive yourself to the Phoenix Office location for the On-site Visits 1 and 2 (if applicable) located at the Exponent Phoenix Office.

Exclusion Criteria:

• Being pregnant or attempting to become pregnant
• Having medical implants, such as a pacemaker or metal joint replacements, or other metal implants contraindicated for MRI
• Cosmetic implants, such as breast implants
• Having a height greater than DXA scanning limit (77 inches)
• Having a body weight greater than indicated for the equipment (400 lbs)
• Prior amputation or major body-altering surgery that could invalidate body composition estimates
• Having claustrophobia or a history of claustrophobia
• Known HIV infection
• Known Lipodystrophy
• Known hydration abnormality (e.g., significant edema, end-stage renal disease, end-stage liver disease)
• Severe illness or life-threatening conditions such as end-stage kidney, liver, lung disease, NYHA III-IV heart failure, or active malignancy