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UTILITY OF AN ORAL PRESENTATION OF hCG (human Choriogonadotropin) FOR THE MANAGEMENT OF OBESITY.
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CONTENTS
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DATA ANALYSIS
Variables were splitted as follows for a better data processing and
statistical results presentation:
· Category I, BW plus four bioelectrical
impedance records (FW, LW, WW and CAL),
· Category II, eight anthropometrical
measurements (corporal circumferences WRT, BRE, WAT, ABD, HIP, THI,
ROT and ANK).
· Category III, nine skinfold assessments (TRI,
AXA, SCA (I), TOR, ILI, UMB(u), UMB(l), THI, ROT) (see long names
and definitions for the studied variables at the beginning of this
section).
Each set was analyzed with a two-way multivariate analysis of
variance (MANOVA), comparing the obtained Wilks-lambda' F with the
corresponding critical value.
TREATMENT (VLCD diet plus group-specific pharmacological
intervention) was considered the between-subject factor with three
levels (P, G1, G2), and WEEK of clinicometric control served as an
additional within-subject factor with six levels: weeks 0 to
5.
To estimate how the differences between treatment' groups depended
on the trial time elapsed since week zero (comparison of pattern
trend changes in function of treatment time) we obtained the MANOVA
result for the effect of the INTERACTION (also displayed in the text
as TREATMENT x WEEK).
Moreover, to prevent any possible influence of acute effects
specifically associated to any VLCD program in the adaptation phase
(first 5-7 days), we additionally evaluated with separate MANOVA
analyses the differences between groups and within subjects in the
course of the last four treatment's weeks.
After obtaining a statistically significant multivariate test for a
particular main effect or interaction, we further examined the
univariate F tests for each dependent variable. When parameters from
these tests displayed significant modifications, data were further
analyzed to ascertain which group (P, G1 or G2) was the responsible
for the previous p values obtained.
We also compared data basal values from each group against those
obtained in subsequent weeks (e.g., records of week 0 against week
1, thereafter against week 2, and so on). These pairwise comparisons
were statistically assessed applying a post hoc Scheffé F tests.
Questionnaire responses were converted into percentages and
submitted to a chi-square (2c) test to compare between-groups and
within-groups (pairing off final vs. initial data) statistic
results.
To attenuate the natural source of within-subject variation,
inherent to all assessments of subjective symptoms, we averaged data
results from identical questionnaires completed weekly during the
initial first two study weeks. Thus, we obtained a more precise
"initial questionnaire" (avoiding the potential
"adaptation effect" common to any VLCD regime in the first
treatment week).
To obtain the final mood behavior results over the last two
treatment weeks, they were averaged using the same schema as
detailed before. Criteria for significance was p<0.05. Statistica
4.2 (from StatSoft, Inc.) for Windows software was used in all
statistical processing.
RESULTS
(Figures
1, 2, 3
,4 and 5)
All volunteers were submitted to the same VLCD schedule lasting five weeks. The objective of this
study was to gather data on the potential synergism between hCG administration and a VLCD plan. At the end of the study we counted a total of 4.3 % missing data due to the absence of subjects in control days (no one absent in more than two opportunities) as a consequence of personal situations not associated with the experimental conditions. No statistic differences were obtained between Placebo and hCG groups regarding missing data.
1. Regarding weight loss, similar results (with/without hCG administration) were obtained. Bioelectrical impedance exhibited discrete modifications.
As expected, for all types of clinicometric assessments, significant results were obtained through MANOVA analysis on factor
WEEK. Figures 1
and 2 (bioelectrical impedance and anthropometrical data, respectively) show that the time-dependent changes were uniformly present in all tested groups. We therefore estimated that the decreasing observed patterns were the consequence of VLCD acting upon overweight patients. However, regarding skinfold thickness findings
(Figures 3 and 4), we detected in P group a noticeable tendency to attenuation of the within-subject variation during the last (third to fifth) study weeks.
This data suggested us that this latter period might be the focus of our interest (see detailed analysis below).
Figure 1 shows data patterns resulting in all groups from three representative variables (BW, FW and LW) of the variable category I. The MANOVA analysis revealed nearly significant differences for the INTERACTION (TREATMENT x WEEK) [F(50,58) =1.35 , p=0.13] in the absence of statistical significance on analysis of TREATMENT as main effect [F(10,98)=1.22, p=0.29].
When all groups were submitted to multivariate and univariate analyses taking exclusively data from weeks 2-5, we observed no significant difference result for the INTERACTION between group P and hCG-treated groups. This finding could be related to differences in mean basal body weights and treatment-dependent responses to the acute effects of VLCD during former
weeks.
When post hoc Scheffé test was applied to compare the result from each weekly record (weeks 1-5) to its corresponding basal value (week zero), we found similar patterns for all groups concerning analysis of BW and TBI records (compare P vs. hCG-treated groups in every panel of Figure 1).
However, regarding the analysis of FW and BW data, we detected significant differences for the effect of the INTERACTION (p<0.005 and p<0.05, respectively). Comparing FW patterns from groups P and G1: F (5,230)=4.55, p<0.001. For the comparison P vs. G2, (BW and FW data), we obtained: F(5,140)=4.20 and 2.97, respectively (p<0.01 for both cases).
2. Ability of hCG to enhance diet-induced decreasing of waist and abdominal circumferences.
Figure 2 shows the results for three (category II) body circumference assessments (WAT, ABD and HIP). MANOVA analysis showed significant differences for factor TREATMENT as main effect [F (16,92)=1.92, p<0.04], which we do not consider relevant due to the presence of higher basal records in group G2 when compared to the rest of the studied groups.
As a whole, the effect of the INTERACTION did not reveal statistical significance.
Nevertheless, significant differences were obtained after further analysis for the effect of the INTERACTION upon variable WAT [F (10,265)=2.44, p<0.01, see panel A].
Data assessments from other circumferences did not show statistical differences for this effect between groups [as representative examples, see ABD (p=0.35) and HIP records in panels B and C, respectively].
When the records of weeks 0-1 were subtracted from MANOVA analysis, almost all p values were slightly affected. WAT and ABD measurements demonstrated to be still more affected by the INTERACTION: for WAT, p<0.003; for ABD, p<0.08. The INTERACTION significance increased when P controls were compared to subjects from group G2: comparing P vs. G2, and considering data from weeks 0-5, we obtained: F (5,140)=2.87 (p<0.02) for WAT, and F(5,140)=1.80, (p=0.12) for ABD. But when we analyzed data from weeks 2-5, we found the following: for WAT, F (3,84)=3.43 (p<0.02), for ABD, F (3,84)=2.73 (p<0.05).
3. Weak effects of hCG on a series of skinfold thickness reductions
patterns.
Figures 3
and 4 show results
from subcutaneous fat evaluations, as assessed by skinfold thickness, on
nine selected skinfolds.
Figure 3 presents three representative
folds [TRI, SCA (l), ILI (u)] out of five (those previous mentioned plus
AXA and TOR) that demonstrated to be slightly affected by the
pharmacological treatment.Analyzing skinfold data from weeks 0 to 5,
the main effect TREATMENT showed statistical significance (F(10,98)=2.39,
p<0.02).
However, prevailing higher basal records in group G2 might account for
this statistical significance. After studying the effect of the
INTERACTION on skinfold results, statistics were as follows: TRI (see
panel A), p<0.08; AXA, p=0.98; SCA (l) (see panel B), p<0.005; ILI
(see panel C), p=0.23; TOR, p=0.35.
Performing pairwise comparisons between control P and hCG-treated groups,
we observed that the higher significances obtained for SCA (l) and TRI
skinfolds derived mainly from the comparison between P and G2: for TRI, F
(5,140)=2.55, p<0.04, for skinfold SCA (l), F (5,140)=6.02,
p<0.0001.
MANOVA analysis run on weeks 2-5 data resulted in a significance increase
for TREATMENT as main effect [F (10,98)=2.55, p<0.009]. In addition,
the INTERACTION was enhanced on data from SCA (l) assessment
(p<0.00005): by comparing data from groups P and G2 during weeks 2 to
5: for TRI, F (3,84)=2.08 (p<0.04), for SCA (l), F (3,84)=9.31.
4. Higher response rates in a different skinfold series by treatment with hCG plus a VLCD
In Figure 4 we display skinfold
thickness results obtained from another series of four examined skinfolds
[UMB (u), UMB (l), THI, ROT (u)]. MANOVA analysis resulted in a nearly
significant INTERACTION [F (40,68)=1.55, p<0.06] in the absence of
statistical significance for TREATMENT as main effect [F(8,100)=1.43,
p=0.20].
When the specific effect of the INTERACTION was evaluated for each
skinfold, highly significant differences were found. By computing F
(10,265) values, we obtained the following results: UMB (u) (see panel A),
p<10-3; UMB (l) (see panel B), p<10-5; ROT (see panel C), p<0.05;
THI (see panel D), p<10-6. When we restricted the data analysis from
weeks 2 to 5, we found nearly significant results for factor TREATMENT as
main effect [F (8,100)=1.75, p<0.1] and for the effect of the
INTERACTION [F (24,84)=1.55, p<0.06].
The INTERACTION was further studied pairing P group against each
hCG-treated group in separate multivariate analyses. By comparing P vs.
G1, we found: for UMB( l) , p<0.04, and for ROT , p<0.03 (UMB(u) and
THI achieved nearly significant p values). Again, the strength of the
INTERACTION [TREATMENT x WEEK] was higher when group G2 was selected for
the comparison.
From the obtained data, it becomes clear that skinfolds determinations in
G2 subjects showed a differential response to VLCD schedule with respect
to that of P controls (for INTERACTION, in these points of skinfold
assessment, p<0.0005).
5. The selective response of some skinfolds to hCG was suggestive to be dependent on dose
The experimental design of this investigation was not intended to
determine the dose-response curve for hCG acting on diet-induced
effects.
However, the effects of hCG on some of these skinfolds seemed to be
dependent on dose, since it was found significant differences for the
effect of the INTERACTION after the comparison between G1 vs. G2 groups
for UMB (u) (p<0.001) and UMB (l) (p<0.005), and a nearly
significant p value for THI (p=0.11).
Figure 4 also displays the percentages
of skinfold thickness reduction from the beginning to the end of the
clinical trial. We found skinfolds decreases for group G1 ranging from
over 22% (for UMB (u), see panel A) up to over 115% (for THI, see panel D)
over respective decreases in P group.
These differences were still higher when G2-subjects were compared to P
controls: by computing the ratio between decrease percentages, G2 had over
twice (for UMB (u), see panel A) to over four-fold (for THI, see panel D)
the skinfold records drops observed in group P (see each actual
percentage, group by group, in Fig. 4).
Most of the differences between hCG-treated subjects and P controls
regarding skinfold reduction rates were enhanced when data corresponding
to week five was compared to records of week two instead week zero (data
not shown).
6. Improvement of mood-related parameters by the effect of hCG treatment
In Figure 5 we display the responses to
four representative questions asking about the occurrence frequency for
specific mood-related events, according to a multiple choice designed
questionnaire completed every treatment week by all the subjects enrolled
in the trial.
Panels A to D display the initial and final questionnaire results,
expressed as percentages for each optional response (covering a
four-option frequency scale from never to frequent).
Using this procedure, we expected to find in tested volunteers skewness
towards either sense concerning their behaviors and feelings in response
to a diet and a pharmacological intervention. For all these questions, and
compared to control subjects, hCG-treated volunteers (G1+G2) showed a
trend to improvement of inter-personal contacts and mood control when
confronting upsetting or conflicting situations.
Pairing off final (f) vs. initial (i) distribution of percentages for
optional responses, we particularly found statistical significance in two
of these questions in group G (after 2c test: 2c3=16.3, p<0.002, and
2c3=7.82, p<0.05; see right sectors of panel A and B,
respectively).
P group-subjects did not present temporal differences (see panel A), or
were adversely affected in their mood during the trial 2c3=14.4,
p<0.002 (compare in panel B corresponding initial and final values for
group P and G).
Furthermore, group P exhibited in other two questions certain skewness to
the impairment of its mood (see left half of panels C and D, p<10-5 );
for group G we obtained the 2c3 values 1.51 and 3.98, respectively
(p>0.3), indicating the absence of temporal mood changes.
For all other mood-related questions, no statistical significant
difference between groups was found (data not shown).
We also included some questions intended to evaluate the potential
occurrence of treatment-dependent clinical anomalies regarding hormonal,
physiological or metabolic disorders. We found no significant difference
after final vs. initial records' comparison (data not shown).
7. No detectable b-hCG plasmatic levels in all tested groups.
On treatment days 0, 15 and 30 we have tested all volunteers, screening
for the presence of plasmatic b-hCG. Concentrations were undetectable in
all cases (data not shown).
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(Materials and methods, Clinicometric controls) |
(Discussion,Conclusions, References) |
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