|
MATERIALS AND METHODS
This pivotal phase II clinical trial, conducted at five centers (2 in the USA, 1 in the UK and 2 in Japan) between August
2004 and June 2005, was approved by the relevant institutional review boards/ethics committees for the protection of human subjects. All
participants provided informed consent prior to their enrollment in the study.
Screening and Enrollment
One hundred and sixty four (164) healthy volunteers were enrolled in this prospective, multi-center, comparative study designed
to assess safety and efficacy of a single treatment with the Contour I™ system (UltraShape Ltd., Israel) at different body areas (abdomen, thighs,
or flanks). One hundred and thirty seven (137 total; 25-30 at each clinical site) participants were assigned to the experimental (treated) group
and twenty seven (27; 5-6 at each clinical site) participants to the control (untreated) control group. The male-to-female participant ratio was
1:2. Participants were aged 18-65 years and had subcutaneous fat thickness of at least 1.5 cm in the area to be treated, as measured with a
commercial pinch caliper. At the screening visit subjects underwent physical examination and liver ultrasound, and serum was isolated from whole
blood via venipuncture for laboratory testing. Individuals with cardiac pacemakers, abdominal wall hernias, pregnancy, diabetes, hepatitis, HIV
positivity, coagulation disorders or recent ingestion of anticoagulants, history of exposure to highly fat-soluble compounds, as well as subjects
who failed the screening testing were excluded. Females of child-bearing potential were enrolled only if using two methods of contraception.
Treatment area assignment was dictated by clinical assessment of each subject by the investigator.
Measurements
Immediately prior to the procedure (Day 0), the area to be treated (abdomen, thighs, or flanks) was marked and fat thickness in
the marked area was confirmed by the investigator to be at least 1.5 cm with a pinch caliper. Each participant was weighed and measured for
circumference (cm) at the treatment area and at the internal control area (thigh). Circumference was measured via a standardized measuring
technique using a specially designed and validated apparatus that provides measurements at a constant height and under constant tension. Ultrasound
assessment of fat thickness (mm) was performed with a specially-designed apparatus that held the diagnostic ultrasound transducer on the skin at a
constant pressure. Photography was performed with a dedicated 35-mm camera, set at fixed focal length and under constant lighting.
Treatment with the Contour I™
A topical anesthetic (EMLA Cream - lidocaine 2.5% and prilocaine 2.5%; AstraZeneca) was applied under occlusion for 90 minutes before
the procedure. The EMLA cream was removed and a skin-compatible treatment oil, provided by the manufacturer, was applied to serve as an acoustic
coupling medium. Treatment was applied using the manufacturer's pre-set and unchangeable settings. Pulse oximetry was assessed throughout the procedure.
The treatment was performed using a handpiece whose positioning was monitored and guided by the Contour I™ real-time video tracking
and guidance system. This tracking system directs the user's movement of the transducer to the immediately adjacent treatment position so that each
area within the marked treatment area is treated once and only once, thereby ensuring uniform and homogeneous energy delivery throughout the entire
marked treatment area (Figure 1).
The treatment lasted 60-120 minutes, depending on the size of the treatment area. A fixed energy dose, preset as a single spot or
"node" energy dose, was delivered per unit surface area treated. The experimental group received a single Contour I™ treatment on Day 0. Control
values were derived from subjects who were untreated but followed over the time of the protocol. No subject underwent a sham procedure. After
treatment, participants were instructed to resume regular daily activities and eating habits to maintain baseline body weights. Follow-up visits
for both experimental and control groups were scheduled on Days 1, 3, 7, 14, 28, 56, and 84.
Efficacy Assessments
At each follow-up visit, participants underwent photography, weighing, and measurement of the circumference of the treated and
internal control areas. The untreated thigh was used as an internal control to indicate circumference changes that were unrelated to treatment,
for example induced by weight loss. Change in circumference was assessed as the difference between circumferences measured at follow-up visits
(Days 1, 3, 7, 14, 28, 56 and 84) and the pre-treatment circumference (Day 0). Ultrasound measurements of subcutaneous fat thickness were
performed before treatment (Day 0) and on Days 14 and 28.
Safety Assessments
Safety assessments included laboratory testing, pulse oximetry, liver ultrasound, and adverse event monitoring. The laboratory
evaluation included complete blood count, chemistry (sodium, potassium, creatinine, urea, calcium), fasting lipids (total cholesterol, HDL, LDL,
and triglycerides), liver markers (ALT, AST, LDH, alkaline phosphatase, total bilirubin, albumin), as well as complete urinalysis. These
parameters were recorded at all study visits (Days 0, 1, 3, 7, 14, 28, 56 and 84). Pulse oximetry was continuously monitored during the Contour
I™ treatment and was measured before and after treatment and on Day 1 to assess potential pulmonary adverse effects. Liver ultrasound was
performed before treatment and at Day 14 and 28 to identify treatment-induced fatty infiltration of the liver. Adverse event occurrence was
monitored throughout the study. Two-point discrimination testing was performed at baseline and at Day 28.
Statistical Analysis
Circumference reduction and fat thickness reduction from the three treated body areas were combined for analysis. Data were
analyzed using SAS software (SAS Institute, Cary, North Carolina). All tests applied were two-tailed, and a p-value of ?0.050 was considered
statistically significant. Within each group, the paired t-test was applied for testing differences between baseline (Day 0) assessment and
follow-up assessments for quantitative parameters. The two-sample t-test was applied for testing differences between the treated and untreated
study groups for quantitative parameters (fat thickness reduction and circumference reduction, participant demographics). The data were
expressed as mean and standard error of the mean.
Click here to read more on the Contour ITM
|
