Download Bangor, Maine and Coordinating Center

245 Bradley Street
Saco, ME 04072
(207) 571-4380
SUMMARY OF SAFETY ASSESSMENT
The 2005 Clinical Trial to Test the Short-Term Efficacy, Safety, and Dosing
of Asia Biotech’s DS-AA**
**Dietary Supplement to Reduce the Signs and Symptoms of Aging
Prepared By:
Marshall-Blum, LLC
James M. Blum, Ph.D., CEO, Principal Investigator
Assistant Professor, University of New England, College of Medicine,
Dept. of Epidemiology and Biostatistics, Biddeford, ME
Adjunct Faculty, University of Maine, Department of Food Sciences and Human
Nutrition
Adjunct Faculty, Husson College, College of Arts and Sciences
Cardiac Quality Improvement Consultant, Eastern Maine Medical Center
Member, Northern New England Cardiovascular Disease Research Group,
Dartmouth-Hitchcock Medical Center
Member, Health Services Research Group, Case Western Reserve University,
Department of Epidemiology and Biostatistics
[email protected]
Co-Investigator:
Ronald I. Blum, M.D. (no relation)
Fellow, American Academy of Family Physicians
Fellow, American College of Occupational and Environmental Medicine
Immediate Past President, Maine Academy of Family Physicians
2003 Maine Family Physician of the Year
Board of Directors, New England College of Occupational and Environmental Medicine
Island Falls, Maine
November 17, 2006
Sponsor:
Asia Biotech Corporation
Noel Thomas Patton, Chairman & Managing Director
C/o Asia Biotech Company, Inc.
David Cross, Executive Vice President & General Manager
1120 Avenue of the Americas, 4th Floor
New York, New York 10036
(212) 626-6872
(212) 626-6873 (fax)
[email protected]
Clinical Site where the Trial was Conducted:
Bangor, Maine and Coordinating Center:
Marshall-Blum: Clinical Outcomes Specialists
Herbal Research Clinic
268 State Street
Bangor, Maine 04401
Independent Medical Research Clinic
Institutional Review Board (IRB) Approved Clinical Trials
James M. Blum, PhD, Study Coordinator, Epidemiologist and Biostatistician
Medical Director: Ronald I. Blum, MD
Current Mailing Address:
Southern Maine Clinical Research Center
245 Bradley Street
Saco, Maine 04072
(207) 571-4380
(207) 299-5411 cellular
[email protected]
jblum@so_mecrc.com
CLINICAL TRIAL SUMMARY
The 2005 Anti-Aging Trial of TA-65 was a double blind, placebo controlled, 24 week
study in which subjects consumed 2 or 4 tablets daily of a placebo control substance
(placebo groups) for 12 weeks or 2 or 4 tablets daily of a TA-65 precursor molecule (TA41) for 12 weeks (product groups). The product tablets each contained 10 mg of TA-41
(an Astragalus extract) along with other botanical extracts and excipients. [The upper
dose of 40 mg. TA-41 daily is essentially equivalent to a daily dose of 5 mg. of TA-65.]
The placebo control tablets were essentially indistinguishable from the product tablets in
appearance and taste, even when the tablet was broken. The 12 week placebo or product
use period was followed by a further 12 week follow-up period. To ascertain active
substance in the blood (for compliance and to better understand the relationship between
TA-41 and TA-65), analytical measurements TA-41 and TA-65 (the presumed major
metabolite of TA-41) were conducted at 6 weeks and 12 weeks. Thirty six male subjects
aged 60-85 who expressed an interest in reducing the signs and symptoms of aging and
who reported a gradual decline in overall energy levels at the screening visit were
recruited. Subjects were randomly assigned to the placebo group (n=6 taking two placebo
tablets, one in the morning, one in the evening; n=6 taking 4 placebo tablets, two in the
morning, two in the evening) or the product treatment group (n=12 taking two product
tablets, one in morning, one in evening; n=12 taking 4 product tablets, 2 in morning, 2 in
evening). Subjects were assessed at baseline and at 6 weeks, 12 weeks and 24 weeks
from the first dose of product.
Clinical Trial Population
Thirty-six (36) subjects were screened and enrolled in this trial. All subjects
signed an approved informed consent form and met all of the following entrance
criteria:
 Men who wanted to reduce the signs and symptoms of aging;
 Men who reported a chronic, noticeable, and gradual decline in overall
energy levels by answering two of three questions positively;
 Men who were 60 to 85 years of age, inclusive, at the Initial Visit.
In the screening process, potential subjects were excluded if they were allergic to
or expressed problems with ingredients in the DS-AA or placebo. Subjects were
excluded if they were known to have severe co-morbid disease including cardiac,
pulmonary, renal, hepatic, or active cancer. Subjects who had used any
prescription or non-prescription products to reduce the signs and symptoms of
aging within the past 4 weeks were excluded.
Potential subjects were excluded if they consumed alcohol at an elevated level,
were insulin dependent diabetic, had uncontrolled hypertension, had a Body Mass
Index (BMI) of greater than 40 m/kg2, took methadone, insulin, anticoagulants, or
similar medications; or had any disease or condition that in the principal
investigator’s opinion compromised the integrity of the clinical trial or the safety
of the subjects.
OBJECTIVES
To evaluate the supportability of the following structure-function claims:






reduce the signs and symptoms of aging;
promote healthy immune function;
promote healthy muscles;
promote healthy bones;
help maintain a healthy hormone balance;
and use as part of the diet to maintain a healthy blood sugar level.
through short-term efficacy, safety, and dosing testing of Asia Biotech’s DS-AA
in human subjects.
Safety Measurements
The safety measurements are (1) adverse events;
(2) laboratory testing of:
 complete blood count with auto differential (CBC w/auto diff.),
 comprehensive metabolic panel (CMP),
 and reticulocyte count with immature reticulocyte fraction (retic.).
and (3) research staff measurements of:
 tolerability,
 weight,
 blood pressure,
 pulse,
 and respirations.
The assessment of research staff measurements of weight, blood pressure,
pulse, and respirations will be compared within subjects from
measurements at the Initial Visit, baseline, 6 weeks, 12 weeks and 24
weeks. The assessment of laboratory testing will be compared within
subjects from measurements at baseline, 6 weeks, 12 weeks, and 24
weeks. The assessment of adverse events and research staff measurements
of tolerability will be compared within subjects from reports and
measurements at 6 weeks, 12 weeks, and 24 weeks.
Research staff measurements of weight, blood pressure, pulse,
respirations, and tolerability will be conducted according to the applicable
section in the SOP (14. Product and Placebo Tolerability, 16. Safety
Measurements, 17.1 Weight as a Safety Measurement).
TRIAL RESULTS
Physiological Indicators
SBP B1
SBP B2
SBP B3
DBP B1
DBP B2
DBP B3
Pulse B1
Pulse B2
PulseB3
Resp B1
Resp B2
RespB3
Placebo
0.82 (9.1)
0.27 (8.7)
- 2.8 (11.9)
- 0.36 (9.6)
- 1.09 (6.9)
- 4.3 (8.8)
1.7 (4.3)
0.09 (4.6)
0.11 (6.0)
0.18 (0.4)
0.18 (0.4)
0.22 (0.4)
Product
- 2.3 (10.6)
- 0.36 (12.1)
- 0.47 (9.2)
- 0.82 (7.4)
- 1.45 (7.9)
0.63 (9.5)
1.8 (6.6)
3.6 (7.4 )
4.6 (5.2)
- 0.08 (0.4)
- 0.09 (0.4)
0 (0)
P Value
0.40
0.88
0.58
0.88
0.90
0.20
0.96
0.16
0.054
0.085
0.27
0.22
Weight Outcomes
Weight B1
Weight B2
Weight B3
Placebo
- 1.8 (4.5)
- 1.6 (5.0)
- 1.8 (4.5)
Product
- 2.6 (5.2)
-0.4 (5.5)
- 2.6 (5.2)
P Value
0.70
0.52
0.70
Discussion of Physiological Parameters
There are no differences in the SBP between those on placebo and those on product at
either baseline or at any of the three follow-up time periods. The largest difference was
observed at 6 weeks and was only 2.3 torr higher than baseline. This represents a 1.8%
increase over baseline, which is not a clinically significant difference.
There are no differences in the DBP trend for those on product. There is a slight increase
in the placebo group (4.33 torr over baseline). The differences were not statistically
different which shows that small differences could represent a placebo effect.
Accordingly, there is nothing negative to report for either SBP or DBP.
However, there is a slight difference in the pulses. There was a consistent trend for the
men on product of reducing their average pulse from 1.8 to 3.5 to 4.3 from baseline. The
24 week comparison was statistically different compared to placebo using the difference
of means test. If this is real, a compound that reduces pulses in older men a little may be
a good thing. However, the chi-square test was not different.
Safety Blood Labs
WBC 6 wks
WBC 12 wks
WBC 24 wks
RBC 6 wks
RBC 12 wks
RBC 24 wks
Hemoglobin 6 wk
Hemoglobin 12 wk
Hemoglobin 24 wk
Hct 6 wk
Hct 12 wk
Hct 24 wk
MCV 6 wk
MCV 12 wk
MCV 24 wk
MCH 6 wk
MCH 12 wk
MCH 24 wk
MCHC 6 wk
MCHC 12 wk
MCHC 24 wk
Platelets 6 wk
Platelets 12 wk
Platelets 24 wk
RDW_SD 6 wk
RDW_SD 12 wk
RDW_SD 24 wk
RDW_CV 6 wk
RDW_CV 12 wk
RDW_CV 24 wk
Neutrophils 6 wk
Neutrophils 12 wk
Neutrophils 24 wk
Lymphs 6 wk
Lymphs 12 wk
Lymphs 24 wk
Monocytes 6 wk
Monocytes 12 wk
Monocytes 24 wk
Basophils 6 wk
Basophils 12 wk
Basophils 24 wk
Placebo
0.05 (0.9)
- 0.36 (1.7)
0.1 (0.6)
0.03 (0.1)
0.12 (0.2)
- 1.1 (0.6)
- 0.01 (0.4)
0.3 (0.6)
- 0.5 (0.7)
0.6 (1.8)
1.3 (2.2)
- 0.3 (2.4)
0.7 (2.4)
0.4 (2.2)
0.5 (3.2)
- 0.25 (0.7)
- 0.21 (0.5)
- 0.23 (1.3)
- 0.5 (1.4)
- 0.35 (1.1)
- 0.88 (1.5)
-12.0 (30.6)
-12.2 (21.6)
- 3.25 (22.2)
0.65 (1.7)
0.65 (2.0)
0.85 (1.8)
- 0.02 (0.5)
0.08 (0.5)
- 0.11 (0.4)
- 1.27 (4.7)
- 1.73 (7.5)
2.63 (6.3)
0.55 (3.4)
0.55 (6.6)
- 2.88 (5.9)
1.36 (2.9)
1.45 (3.0)
0.13 (1.5)
0 (0)
0.14 (0.4)
- 0.2 (0.4)
Product
0.13 (1.0)
- 0.37 (1.1)
0.1 (1.1)
0.02 (0.2)
0.002 (0.2)
-1.1 (1.4)
0.02
- 0.07 (0.6)
- 0.4 (0.8)
0.2 (1.7)
0.6 (2.0)
- 0.1 (2.5)
0.15 (1.7)
1.2 (1.3)
1.7 (2.3)
- 0.06 (0.4)
- 0.17 (0.7)
- 0.21 (0.9)
- 0.14 (0.7)
- 0.66 (1.0)
- 0.87 (0.8)
1.30 (22.2)
- 2.76 (24.8)
1.06 (31.9)
0.88 (2.0)
0.69 (1.9)
1.0 (2.0)
0.31 (0.6)
0.16 (0.6)
0.05 (0.6)
0.17 (3.6)
- 1.27 (6.6)
1.06 (5.2)
- 0.78 (2.9)
- 0.32 (4.9)
- 1.65 (5.2)
0.22 (1.2)
0.64 (1.5)
- 0.06 (1.7)
0 (0.4)
0.13 (0.4)
0.08 (0.3)
P Value
0.81
0.99
0.96
0.80
0.12
0.91
0.89
0.12
0.81
0.50
0.38
0.87
0.49
0.17
0.29
0.29
0.86
0.94
0.42
0.42
0.99
0.16
0.30
0.73
0.74
0.96
0.86
0.11
0.69
0.40
0.33
0.86
0.52
0.25
0.67
0.60
0.23
0.41
0.79
1.0
0.95
0.13
Labs Page 2
EOS 6 wk
EOS 12 wk
EOS 24 wk
Sodium 6 wk
Sodium 12 wk
Sodium 24 wk
Potassium 6 wk
Potassium 12 wk
Potassium 24 wk
Chloride 6 wk
Chloride 12 wk
Chloride 24 wk
CO2 6 wk
CO2 12 wk
CO2 24 wk
Anion 6 wk
Anion 12 wk
Anion 24 wk
BUN 6 wk
BUN 12 wk
BUN 24 wk
Serum Cr. 6wk
Serum Cr 12 wk
Serum Cr 24 wk
BUN/SCR 6 wk
BUN/SCR 12 wk
BUN/SCR 24 wk
Glucose 6 wk
Glucose 12 wk
Glucose 24 wk
Tot Protein 6 wk
Tot Protein 12 wk
Tot Protein 24 wk
Albumin 6 wk
Albumin 12 wk
Albumin 24 wk
Globulin 6 wk
Globulin 12 wk
Globulin 24 wk
Placebo
- 0.63 (1.2)
- 0.09 (1.4)
0.25 (1.0)
- 1.27 (2.6)
- 0.36 (2.2)
1.5 (1.9)
- 0.05 (0.4)
0.04 (0.4)
0.04 (0.2)
- 0.09 (2.4)
0.18 (2.6)
1.88 (2.9)
- 1.53 (5.0)
- 2.21 (3.9)
- 1.24 (4.9)
0.45 (4.5)
1.82 (3.2)
1.0 (3.3)
2.18 (3.4)
1.18 (4.4)
0.56 (3.9)
0.0091 (0.07)
0.0091 (0.08)
- 0.063 (0.119)
2.35 (4.5)
1.25 (5.5)
2.6 (5.5)
- 2.0 (8.9)
- 1.55 (9.6)
- 3.5 (11.4)
0.06 (0.3)
- 0.09 (0.6)
- 0.28 (0.4)
- 0.11 (0.4)
- 0.05 (0.4)
- 0.11 (0.4)
0.17 (0.4)
- 0.04 (0.6)
- 0.19 (0.2)
Product
0.43 (3.1)
0.82 (3.3)
0.53 (3.4)
- 0.22 (1.8)
- 0.22 (2.1)
0.89 (1.2)
- 0.07 (0.4)
- 0.03 (0.3)
0.1 (0.4)
0.34 (2.3)
0.41 (2.6)
1.56 (2.7)
- 1.86 (4.7)
- 3.47 (3.9)
- 3.56 (4.9)
1.26 (5.1)
2.86 (4.1)
2.89 (4.8)
0.96 (7.5)
0.22 (7.5)
- 0.57 (7.9)
- 0.0087 (0.14)
- 0.0182 (0.07)
- 0.094 (0.13)
0.35 (4.4)
- 0.29 (5.9)
- 0.44 (3.8)
0.83 (7.9)
- 1.68 (10.9)
- 6.56 (8.9)
0.14 (0.4)
0.13 (0.4)
- 0.03 (0.5)
- 0.02 (0.2)
- 0.02 (0.2)
- 0.06 (0.3)
0.16 (0.3)
0.15 (0.4)
0.04 (0.3)
P Value
0.28
0.40
0.83
0.18
0.87
0.33
0.83
0.58
0.69
0.62
0.81
0.79
0.85
0.39
0.79
0.66
0.47
0.32
0.61
0.70
0.69
0.70
0.34
0.56
0.23
0.48
0.11 **
0.36
0.97
0.47
0.56
0.23
0.23
0.33
0.70
0.70
0.95
0.26
0.085 **
Labs Page 3
Alb/Globulin 6 wk
Alb/Globulin 6 wk
Alb/Globulin 6 wk
Bilirubin 6 wk
Bilirubin 6 wk
Bilirubin 6 wk
Calcium 6 wk
Calcium 12 wk
Calcium 24 wk
Alk Phos 6 wk
Alk Phos 12 wk
Alk Phos 24 wk
AST 6 wk
AST 12 wk
AST 24 wk
ALT 6 wk
ALT 12 wk
ALT 24 wk
Retic 6 wk
Retic 12 wk
Retic 24 wk
A1c 6 wk
A1c 12 wk
A1c 24 wk
Placebo
- 0.15 (0.3)
- 0.04 (0.3)
0.03 (0.1)
- 0.06 (0.1)
0.06 (0.3)
- 0.03 (0.1)
- 0.31 (0.3)
- 0.09 (0.6)
- 0.19 (0.6)
4.5 (12.9)
2.09 (15.0)
- 2.63 (5.2)
1.91 (7.4)
0.73 (8.2)
- 0.50 (3.8)
1.64 (7.9)
- 0.73 (8.8)
3.13 (4.9)
- 0.009 (0.4)
0.04 (0.4)
0.03 (0.4)
0.04 (0.3)
0.13 (0.3)
0.03 (0.3)
Product
- 0.09 (0.2)
- 0.09 (0.2)
- 0.03 (0.2)
0.01 (0.2)
- 0.01 (0.3)
0.04 (0.2)
- 0.03 (0.5)
0.20 (0.4)
0.05 (0.4)
3.4 (9.9)
0.36 (7.7)
- 1.33 (9.7)
- 0.61 (4.9)
- 2.14 (9.9)
- 1.22 (4.2)
- 0.13 (9.0)
- 0.32 (12.3)
0.22 (3.5)
- 0.02 (0.3)
0.01 (0.3)
0.07 (0.4)
- 0.01 (0.6)
0.03 (0.6)
0.06 (0.6)
P Value
0.48
0.65
0.38
0.19
0.48
0.33
0.10
0.17
0.32
0.80
0.66
0.73
0.24
0.42
0.68
0.58
0.92
0.099
0.94
0.87
0.79
0.80
0.59
0.90
Summary of the blood lab results:
There appears to be few differences in any of these comparisons and none reached a
targeted p value. By chance alone, one would expect five percent to be statistically
different. Of note, BUN and the BUN ratio were lower in the product group. Some other
differences approached the 0.10 level, but they were isolated and were not consistent
across time. For example ALT, a liver enzyme, rose at the 24 week mark making the
comparison different, but the 3.1 reading was inconsistent across time in the placebo
group, while the data for the product group was relatively close to “no change”.
Adverse Events
ID #
003
035
Explanation
Serious Adverse Event: UNRELATED TO TRIAL; Diagnosed with
esophageal Cancer; Drop
Moderate Adverse Event; Subject experienced elevated blood pressure after
taking product; resolved; Drop
Drops
ID #
002
014
Explanation
Withdrew Consent; “Felt he was on placebo and withdrew”
Withdrew Content; His physician had a concern with an herbal supplement;
Drop
Typical pharmaceutical adverse side effects run anywhere from three-to-four percent up
to fifteen-to-twenty percent, especially for the newer targeted drugs. This trial reported a
five percent adverse event, and that was only a moderate non-life-threatening event.
Safety and Tolerance Summary:
Judging from the number of adverse events (n=1), from the physiological
parameters (systolic and diastolic blood pressures, pulse, respiration, and weight),
from the blood labs, and from reports from the nursing staff, the trial was deemed
safe. There were no indications that either treatment dosage presented any
complications or conditions that would be considered ‘suspicious’ or ‘dangerous’.