Printer Friendly

Improvement of accessory symptoms of hypertension by TSUMURA Orengedokuto Extract, a four herbal drugs containing Kampo-Medicine Granules for ethical use: a double-blind, placebo-controlled study.

Abstract

A double-blind, placebo-controlled study was conducted to evaluate the efficacy, safety, and utility of TSUMURA Orengedokuto Extract Granules for Ethical Use (TJ-15) as a treatment for the accessory symptoms of hypertension. Two capsules of the study drug were administered orally 3 times daily (i.e., before meals) for 8 weeks.

Among 265 patients enrolled in the study, 134 were assigned to the TJ-15 group and 131 were assigned to the placebo group, of whom 204 patients (103 in the TJ-15 group and 101 in the placebo group) were included in the efficacy and utility analyze and 251 patients (128 in the TJ-15 group and 123 in the placebo group) were included in the safety analysis.

Efficacy was significantly higher in the TJ-15 group based on the total score for the accessory symptoms of hypertensions which was the primary efficacy endpoint (Wilcoxon's rank sum test, p = 0.013).

When each accessory symptom of hypertension was assessed separately, efficacy was higher for hot flushes and facial suffusion in the TJ-15 group (Wilcoxon's rank sum test, p = 0.034, and 0.022, respectively).

There were no significant differences between the TJ-15 and the placebo groups with respect to the decrease of blood pressure or the antihypertensive effect.

There was also no significant difference between the two groups with regard to the overall safety rating.

The utility rating was significantly higher in the TJ-15 group than in the placebo group (Wilcoxon's rank sum test, p = 0.016).

In conclusion, TJ-15 was superior to placebo with respect to efficacy, safety, and utility for the treatment of accessory symptoms of hypertension.

[c] 2005 Elsevier GmbH. All rights reserved.

Keywords: Orengedokuto; Kampo medicine (Japanese herbal medicine); Double-blind; Placebo-controlled study; Accessory symptoms of hypertension

Introduction

Evidence has been provided by many epidemiological studies that hypertension is a major risk factor for cardiovascular disease and is closely related to the survival of patients. The treatment of hypertension is in high social need. A comprehensive strategy for antihypertensive therapy, including diet, exercise, and medications is widely recommended by many Guidelines including those released by the Guidelines subcommittee of Japanese Society of Hypertension (2000).

On the other hand, hypertension per se is almost asymptomatic so that the patient's quality of life (QOL) is less impaired by hypertension than by other diseases. However, since the treatment of hypertension needs to be continued over the long term, it is important that due consideration be given to the patient's QOL. According to Dimenas et al., higher blood pressure is associated with an increase of emotional problems, sleep disorders, cardiac and gastrointestinal symptoms, and dissatisfaction (Dimenas et al., 1989). The modern lifestyle is stressful and the relationship between stress and hypertension has attracted considerable attention. It has been pointed out that symptoms of hypertension, such as "anger," "tension," "anxiety," and "worries," are partly responsible for hypertension because they cause an increase of sympathetic activity. Attention should also be paid to the impairment of QOL by the adverse effects of antihypertensive therapy. Taken together, the control of symptoms in hypertensive patients cannot be ignored because it may not only improve the QOL but also help to control the blood pressure.

Orengedokuto is a Kampo medicine (Japanese herbal medicine) that has long been used for the treatment of facial suffusion, a burning sensation, headache, excitation, anxiety, and irritability (Otsuka et al., 1986). In clinical practice, Orengedokuto is currently used for the treatment of palpitations, excitement, hot flushes, facial suffusion, and neurosis. The present communication is a report of a double-blind, placebo-controlled study that was conducted to assess the usefulness of TSUMURA Orengedokuto Extract Granules for Ethical Use (TJ-15) for management of the accessory symptoms of hypertension. TJ-15 has already been approved by the Japanese Health, Labour and Welfare as an ethical drug.

Patients and methods

Patient selection

The subjects were selected from among patients with essential hypertension who met all the inclusion criteria and did not fit any of the exclusion criteria (Table 1).

Methods

The protocol of this study is summarized in Fig. 1.

A double-blind, placebo-controlled trial was performed in 2 groups of patients from June 1994 to March 2001. Patients were randomized to the study medications, and the blinding was ensured by the controller (Shuji Takaori). Informed consent was obtained from each patient before entry into the observation period. Following the 4-week observation period, 2 capsules of TJ-15 or the placebo were administered orally to each patient 3 times daily (i.e., before meals) for 8 weeks. Each capsule of TJ-15 contained 0.25 g of a spray-dried powdered extract of Orengedokuto (Tsumura & Co., Japan). The powder was obtained by hot water extraction of the following four medicinal herbs blended at a ratio of 3:2:2:1.5: Scutellariae radix (the root of Scutellaria baicalensis Georg stripped of its periderm), Coptidis rhizoma (the rootstock of Coptis japonica Makino stripped of its roots), Gardeniae fructus (the fruit of Gardenia jasminoides Ellis), and Phellodendri cortex (the bark of Phellodendron amurense Rupr stripped of its periderm). The three-dimensional HPLC of profile of TJ-15 is shown in Fig. 2., revealing that it contains many ingredients.

The severity of 5 accessory symptoms of hypertension (irritability, anxiety, sleep disorder, hot flushes, and facial suffusion) and 4 general symptoms (headache/heavy-headedness, shoulder stiffness, dizziness, and malaise) was classified into the following 4 grades at 2-week intervals during both the observation and treatment periods:</p> <pre> -

Absent (no symptoms are felt or remembered). + Mild (occasional symptoms that are not disturbing). + + Moderate (obvious symptoms, but tolerable). + + + Severe (symptoms that disturb daily activities). </pre> <p>The scores for each accessory symptom of hypertension were calculated according to the criteria shown in Table 2 and were used to compare the severity in Week 0 (end of the observation period), Week 4 (interim evaluation), and Week 8 (final evaluation). The total score for the accessory symptoms of hypertension was calculated by summing the scores for the individual symptoms. The scores for each general symptom were used to calculate a total score for general symptoms in the same way.

Changes of the accessory symptoms of hypertension were assessed by the investigator in Week 4 (interim evaluation) and week 8 (final evaluation) based on comprehensive evaluation of the 5 accessory symptoms. Changes of the general symptoms were evaluated similarly.

The decrease in blood pressure was calculated by subtracting the mean of 2 blood pressure measurements obtained during the latter half of the observation period (immediately and 2 weeks before the start of administration) from the mean of 2 measurements obtained during the latter half of the treatment period (at the end of treatment and 2 weeks before completing treatment).

The antihypertensive effect was classified into 4 grades according to the criteria shown in Table 2:

(1) blood pressure was decreased;

(2) blood pressure tended to decrease;

(3) blood pressure was unchanged;

(4) blood pressure was increased.

The overall safety rating was classified into 4 grades in weeks 4 (interim evaluation) and Week 8 (final evaluation) by making a comprehensive assessment of any adverse reactions observed during the treatment period and the results of laboratory tests:

(1) no safety problems;

(2) some safety problems;

(3) obvious safety problems;

(4) serious safety problems.

The utility rating was classified into 5 grades in Week 4 (interim evaluation) and Week 8 (final evaluation) by making a comprehensive evaluation of the changes of the accessory symptoms of hypertension, the changes of general symptoms, and the overall safety rating:

[FIGURE 2 OMITTED]

(1) very useful;

(2) moderately useful;

(3) slightly useful;

(4) not useful;

(5) contraindicated.

Statistical analysis

The baseline characteristics of the patients were analyzed by Fisher's exact probability test or Wilcoxon's rank sum test. If there was an intergroup bias, candidate variables were adjusted at p < 0.20.

The primary endpoint was assessed using Wilcoxon's rank sum test. When adjustment for demographic characteristics was necessary, the Cochran-Mantel-Haenszel test was used. Analyses were performed with Wilcoxon's rank sum test and Fisher's exact probability test depending on the type of data. Probability values were obtained with two-tailed and the two-tailed level of significance was set at p < 0.05.

Results

Subjects

A total of 265 patients (134 assigned to the TJ-15 group and 131 assigned to the placebo group) were enrolled in this study. Among them, 204 patients (103 from the TJ-15 group and 101 from the placebo group) were included in the efficacy and utility analyze, while 251 patients (128 the TJ-15 group and 123 from the placebo group) were included in the safety analysis. The baseline characteristics of the 204 patients included in the efficacy analysis are shown in Table 3.

Total score for accessory symptoms of hypertension and score for each symptom (Table 4)

TJ-15 showed significantly higher efficacy than placebo on final evaluation of the total score for the accessory symptoms of hypertension (p = 0.013). The mean total score was also higher for TJ-15 than for placebo at the interim evaluation.

The scores for hot flushes and facial suffusion were significantly higher in the TJ-15 group than the placebo group at both the interim and final evaluations. The mean score was higher with TJ-15 than with placebo for each of the symptoms.

Total score for general symptoms and score for each symptom (Table 4)

The total score for general symptoms was significantly higher in the TJ-15 group than in the placebo group at the interim evaluation (p = 0.017). The mean score was also higher with TJ-15 than with placebo at the final evaluation.

The mean score was higher in the TJ-15 group than the placebo for most of the general symptoms.

Overall changes of accessory symptoms of hypertension and general symptoms (evaluation by the investigators) (Table 5)

The rating for the overall changes of accessory symptoms of hypertension (evaluated by the investigators) was significantly higher in the TJ-15 group than in the placebo group at both the interim and final evaluations.

The rating for the overall changes of general symptoms (evaluated by the investigators) was also significantly higher in the TJ-15 group than the placebo group at both the interim and final evaluations.

Utility rating (Table 6)

The utility rating was significantly higher for TJ-15 than for placebo at both the interim and final evaluations.

Reduction of blood pressure and antihypertensive effect (Table 7)

There was no significant difference between TJ-15 and placebo with respect to the decrease of blood pressure or the antihypertensive effect.

Overall safety rating (Table 8)

There was no significant difference between TJ-15 and placebo with respect to the overall safety ratings at the interim or final evaluations.

Discussion

Orengedokuto has been used for the treatment of palpitations, hot flushes, facial suffusion, neurosis, and other symptoms in hypertensive patients, but little objective clinical information is available about its effects apart from occasional case reports.

In a clinical study, which was not conducted in hypertensive patients but in 108 patients with cerebral infarction, Orengedokuto was administered for 12 weeks and a comparison was made between treated and untreated groups. After 12 weeks of treatment, hot flushes, headache/heavy-headedness, shoulder stiffness, coldness of the limbs, and numbness of the limbs showed a significantly higher improvement rate in the treated group (Ito et al., 1991). It is of interest that Orengedokuto was also effective for hot flushes in our study, although the underlying disease was different.

In another clinical study, the effect of Orengedokuto on the microcirculation was investigated in 24 patients. It was found that Orengedokuto decreased the blood pressure and heart rate, improved the whole blood viscosity and plasma transit time, and constricted arterioles in the bulbar conjunctiva (Hayashi, 1991). The results of this study are interesting because the vasoconstrictor effect on microvessels (arterioles in the conjunctiva) may explain the improvement of hot flushes and facial suffusion by Orengedokuto, while the concurrent decrease in blood pressure was related to hemodynamic changes.

A non-clinical study of Orengedokuto showed that it could decrease blood flow in the auricles of rats and could prevent the increment of heart rate, blood pressure, and auricular blood flow due to theophylline administration (Wakita et al., 2002). The results of this study support the beneficial effect of Orengedokuto on hot flushes and facial suffusion. Furthermore, the finding that Orengedokuto decreased heart rate and blood pressure in rats treated with theophylline is interesting from the viewpoint of use in hypertensive patients, since it suggests that the effect on the microcirculation is coupled with antihypertensive activity such as inhibition of sympathetic activation/hypertonia, one of the risk factors for hypertension.

In the present study, there was no significant difference between TJ-15 and placebo with respect to the decrease of blood pressure or the antihypertensive effect. Therefore, the influence of TJ-15 on the accessory symptoms of hypertension does not seem attributable to an antihypertensive action.

On the other hand, an effect of Orengedokuto on blood pressure has been reported previously. When Orengedokuto was administered to patients with chronic cerebrovascular disease and its effect on blood pressure was assessed, the mean blood pressure decreased in all of the patients after treatment (Nagasawa, 1994). In a non-clinical study, Orengedokuto restored the blood pressure to normal in rats with metyrapone- and heat stress-induced mild hypertension (Arakawa et al., 1987). In the present study, there was no significant difference between TJ-15 and placebo with respect, to the decrease in blood pressure or the antihypertensive effect, but a decrease of blood pressure was observed in the TJ-15 group (a decrease of 7.5 mmHg in mean systolic pressure, 4.5 mmHg in mean diastolic pressure, and 5.5 mmHg in mean arterial pressure) that could suggest a slow onset of antihypertensive activity which is characteristics of herbal medicines.

The results of this double-blind trial may have significant implications from the standpoint of the clinical use of traditional herbal medicines like Orengedokuto in accordance with evidence-based medicine, since the data provide scientific and objective evidence of its efficacy and safety.

References

Arakawa, K., Kabaya, K., Cyong, J., Otsuka, Y., 1987. A study about two Kampo prescriptions and dopamine agonists on the hypertension of MHR or SHR. J. Med. Pharm. Soc. Wakan-Yaku 4, 35-42.

Dimenas, E.S., Wiklund, I.K., Dahlof, C.G., Lindvall, K.G., Olofsson, B.K., De Faire, U.H., 1989. Differences in the subjective well-being and symptoms of normotensives, borderline hypertensives and hypertensives. Jpn. J. Hypertens. 7, 885-890.

Guidelines Subcommittee of the Japanese Society of Hypertension, 2000. Guidelines for the Management of Hypertension (JSH 2000), Tokyo.

Hayashi, T., 1991. Modern medical research to "OKETSU" state--studies in microcirculation and hemorhology. J. Kansai Med. Univ. 43, 421-443.

Ito, E., Takahashi, A., Kuzuya, F., 1991. Clinical effects of TSUMURA Oren-gedoku-to on cerebral infarction. Geriatr. Med. 29, 303-313.

Nagasawa, H., 1994. Kampo treatment of cerebrovascular injury. Dementia (Basel) 8, 303-309.

Otsuka, K., Yakazu, D., Shimizu, T., 1986. Standard Practice of Kampo Medicine. Nanzando, Tokyo 86pp.

Wakita, H., Suzuki, N., Miyamoto, K., 2002. Effects of Orengedoku-to and its constituents on the cardiovascular system: investigation of its efficacy in hotflush. J. Traditional Med. 19, 230-237.

K. Arakawa (a,*,1), T. Saruta (b), K. Abe (c,2), O. Iimura (d,3), M. Ishii (e,4), T. Ogihara (f), K. Hiwada (g,5), K. Fukiyama (h,6), M. Fujishima (i,7), Y. Mizuno (j,8), T. Kikuchi (k), S. Takaori (1,9)

(a) Second Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan

(b) Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

(c) Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan

(d) Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

(e) Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

(f) Department of Geriatric Medicine, Osaka University Faculty of Medicine, Suita, Japan

(g) Second Department of Internal Medicine, Ehime University School of Medicine, Matsuyama, Japan

(h) Third Department of Internal Medicine, University of The Ryukyus Faculty of Medicine, Okinawa, Japan

(i) Second Department of Internal Medicine, Kyushu University Faculty of Medicine, Fukuoka, Japan

(j) Department of Internal Medicine, Fujita Health University School of Medicine, Nagoya, Japan

(k) The Sakakibara Heart Institute, Tokyo, Japan

(l) Shimane Medical University, Izumo, Japan

Received 8 January 2004; accepted 17 February 2004

*Corresponding author. Tel.: + 81 92 741 9269; fax: + 81 92 741 9269.

E-mail address: arakawak@jcom.home.ne.jp (K. Arakawa).

(1) Present address: Hukuseikai Kawanami Hospital, Fukuoka, Japan.

(2) Present address: Sendai Social Insurance Hospital, Sendai, Japan.

(3) Present address: JR Sapporo Hospital, Sapporo, Japan.

(4) Present address: The Yokohama Seaman's Insurance Hospital, Yokohama, Japan.

(5) Now emeritus professor at Ehime University.

(6) Present address: Japan Seaman's Relief Association Ekisaikai Moji Hospital, Kitakyusyu, Japan.

(7) Now emeritus professor at Kyushu University.

(8) Now emeritus professor at Fujita-Gakuen University.

(9) Present address: Koseikai Takaori Hospital, Kyoto, Japan.
Table 1. Inclusion and exclusion criteria

Inclusion criteria
 1. Patients who present with any of the five accessory symptoms of
 hypertension (irritability, anxiety, sleep disorder, hot flushes,
 and facial suffusion) at the beginning of the observation period
 that is classified as grade + + (i.e., the symptom is present, but
 is tolerable).
 2. Patients whose mean sitting blood pressure measured twice during
 the latter half of the observation period (immediately and 2 weeks
 before starting administration of the study medication) is 140-179
 mmHg (systolic pressure) or 90-104 mmHg (diastolic pressure) with a
 variation of [less than or equal to]30 mmHg for the systolic
 pressure and [less than or equal to]15 mmHg for the diastolic
 pressure.
 3. Patients who are in Stage I of the WHO Hypertension Classification.
 4. Patients who consent to participate in the study of their own free
 will after being given information about the objective and
 procedures of the study.

Exclusion criteria
 1. Patients with secondary hypertension.
 2. Patients with poorly controlled diabetes mellitus.
 3. Patients with severe hepatic or renal impairment.
 4. Patients with mental disorders, such as severe mental illness or
 depression.
 5. Patients whose accessory symptoms are difficult to evaluate because
 of dementia or other such disorders.
 6. Patients with cerebrovascular disease.
 7. Patients with a history of acute myocardial infarction.
 8. Patients with atrial fibrillation or severe arrhythmia.
 9. Patients with a history of congestive heart failure or angina
 pectoris.
10. Patients with a predisposition to drug allergy.
11. Women who are pregnant, lactating, or wish to become pregnant.
12. Patients with weakness (referred to as asthenia or constitutional
 deficiency in Kampo medical terms).
13. Other patients who are unsuitable for the study in the opinion of
 the investigator.

 Observation period
 Placebo administration
 during observation period
 1 tab X 3/day
 Week -4 Week -2 Week -0
 (End of the
 observation
 period)

Items investigated
Demographic characteristics of patients #
Treatment compliance # #
Severity of accessory symptoms of # # #
hypertension
(irritability, anxiety, sleep disorder,
hot flushes, facial suffusion)
Severity of general symptoms # # #
(headache/heavy-headedness, shoulder
stiffness, dizziness, generalized
weakness)
Sitting blood pressure, pulse rate # # #
Height #*
Body weight #*
Adverse reactions # #
Complications/accidents # #

Laboratory tests
Urinalysis #*
Hematology tests #*
Biochemistry tests #*
Immunological examination #*
Chest X-ray film #*
ECG #*
Ophthalmology #*

Items evaluated
Score for each accessory symptom of
hypertension
Total score for accessory symptoms of
hypertension
Score for each general symptom
Total score for general symptoms
Overall changes of accessory symptoms of
hypertension
(evaluated by the investigator)
Overall changes of general
subjective/objective symptoms (evaluated
by the investigator)
Utility rating
Reduction of blood
pressure/antihypertensive effect
Overall safety rating

 Treatment period
 TJ-15 capsules
 2 cap X 3/day
 Double blind
 Placebo capsules *
 2 cap X 3/day
 Week 2 Week 4 Week 6 Week 8

Items investigated
Demographic characteristics of patients
Treatment compliance # # # #
Severity of accessory symptoms of # # # #
hypertension
(irritability, anxiety, sleep disorder,
hot flushes, facial suffusion)
Severity of general symptoms # # # #
(headache/heavy-headedness, shoulder
stiffness, dizziness, generalized
weakness)
Sitting blood pressure, pulse rate # # # #
Height
Body weight #
Adverse reactions # # # #
Complications/accidents # # # #

Laboratory tests
Urinalysis #
Hematology tests #
Biochemistry tests #
Immunological examination #
Chest X-ray film
ECG
Ophthalmology

Items evaluated
Score for each accessory symptom of # #
hypertension
Total score for accessory symptoms of # #
hypertension
Score for each general symptom # #
Total score for general symptoms # #
Overall changes of accessory symptoms of # #
hypertension
(evaluated by the investigator)
Overall changes of general # #
subjective/objective symptoms (evaluated
by the investigator)
Utility rating # #
Reduction of blood #
pressure/antihypertensive effect
Overall safety rating # #

* : Each measurement is performed only once during the observation
period.

Fig. 1. Outline of the study protocol.

Table 2. Criteria for calculating the score for each accessory and
general symtom of hypertension and for evaluation of the
antihypertensive effect

(1) Score calculation

Week 0 Week 4 or 8 Score

+ + + [right arrow] - 3
+ + + [right arrow] + 2
+ + [right arrow] -
+ + + [right arrow] + + 1
+ + [right arrow] +
+ [right arrow] -
+ + + [right arrow] + + + 0
+ + [right arrow] + +
+ [right arrow] +
- [right arrow] -
+ + [right arrow] + + + -1
+ [right arrow] + +
- [right arrow] +
+ [right arrow] + + + -2
- [right arrow] + +
- [right arrow] + + + -3

(2) Evaluation of the antihypertensive effect

Rate of decrease in blood pressure
Systolic Diastolic
pressure pressure

[greater than or equal to]20 [greater than or equal to]10
19~10 9~5
[+ or -]9 [+ or -]4
[less than or equal to]-10 [less than or equal to]-5

Rate of decrease in blood pressure
Mean blood Evaluation
pressure

[greater than or equal to]13 Decreased
12~7 Slightly
 decreased
[+ or -]6 Unchanged
[less than or equal to]-7 Increased

-: Absent (no symptoms). +: Mild (symptoms occur occasionally, but are
not problematic). + +: Moderate (symptoms are presents but are
tolerable). + + +: Severe (severe (symptoms interfere with daily
activities)). If the classification for systolic and diastolic pressure
does not agree, the classification for mean blood pressure is adopted.

Table 3. Baseline characteristics of the patients

 No. of patients

Sex Male 101
 Female 103
Complication Absent 138
 Present 66
Past history Absent 137
 Present 67
Age 52.3[+ or -]11.0
Height (cm) 160.1[+ or -]9.4
Body weight (kg) 62.9[+ or -]12.8
BMI 24.3[+ or -]3.4

Accessory symptoms of hypertension (severity in week 0)
Irritability - 77
 + 61
 + + 63
 + + + 3
Anxiety - 109
 + 56
 + + 36
 + + + 3
Sleep disorder - 64
 + 41
 + + 89
 + + + 10
Hot flushes - 79
 + 54
 + + 67
 + + + 4
Facial suffusion - 74
 + 60
 + + 66
 + + + 4

General symptoms (severity in week 0)
Headache/heavy headedness - 80
 + 62
 + + 52
 + + + 10
Shoulder stiffness - 60
 + 51
 + + 73
 + + + 20
Dizziness - 160
 + 28
 + + 15
 + + + 1
Generalized weakness - 76
 + 71
 + + 50
 + + + 6

Sitting blood pressure (average of 2 measurements obtained during the
latter half of the observation period)
Systolic pressure (mmHg) 151.7[+ or -]10.4
Diastolic pressure (mmHg) 92.3[+ or -]7.7
Pulse rate (week 0) 74.8[+ or -]10.8

 TJ-15

Sex Male 50
 Female 53
Complication Absent 69
 Present 34
Past history Absent 69
 Present 34
Age 51.2[+ or -]10.9
Height (cm) 160.0[+ or -]9.6
Body weight (kg) 63.4[+ or -]13.7
BMI 24.5[+ or -]3.3

Accessory symptoms of hypertension (severity in week 0)
Irritability - 41
 + 31
 + + 28
 + + + 3
Anxiety - 53
 + 32
 + + 17
 + + + 1
Sleep disorder - 30
 + 25
 + + 45
 + + + 3
Hot flushes - 36
 + 35
 + + 30
 + + + 2
Facial suffusion - 32
 + 31
 + + 37
 + + + 3

General symptoms (severity in week 0)
Headache/heavy headedness - 44
 + 27
 + + 27
 + + + 5
Shoulder stiffness - 29
 + 30
 + + 32
 + + + 12
Dizziness - 78
 + 17
 + + 8
 + + + 0
Generalized weakness - 42
 + 35
 + + 24
 + + + 2

Sitting blood pressure (average of 2 measurements obtained during the
latter half of the observation period)
Systolic pressure (mmHg) 151.1[+ or -]10.8
Diastolic pressure (mmHg) 92.8[+ or -]7.3
Pulse rate (week 0) 76.1[+ or -]11.1

 Placebo

Sex Male 51
 Female 50
Complication Absent 69
 Present 32
Past history Absent 68
 Present 33
Age 53.5[+ or -]11.1
Height (cm) 160.1[+ or -]9.2
Body weight (kg) 62.3[+ or -]11.8
BMI 24.2[+ or -]3.5

Accessory symptoms of hypertension (severity in week 0)
Irritability - 36
 + 30
 + + 35
 + + + 0
Anxiety - 56
 + 24
 + + 19
 + + + 2
Sleep disorder - 34
 + 16
 + + 44
 + + + 7
Hot flushes - 43
 + 19
 + + 37
 + + + 2
Facial suffusion - 42
 + 29
 + + 29
 + + + 1

General symptoms (severity in week 0)
Headache/heavy headedness - 36
 + 35
 + + 25
 + + + 5
Shoulder stiffness - 31
 + 21
 + + 41
 + + + 8
Dizziness - 82
 + 11
 + + 7
 + + + 1
Generalized weakness - 34
 + 36
 + + 26
 + + 4

Sitting blood pressure (average of 2 measurements obtained during the
latter half of the observation period)
Systolic pressure (mmHg) 152.4[+ or -]10.0
Diastolic pressure (mmHg) 91.8[+ or -]8.0
Pulse rate (week 0) 73.3[+ or -]10.3

Values are the mean[+ or -]SD.

Table 4. Total score for accessory symptoms of hypertension and general
symptoms and scores for each symptom

 Interim evaluation
 Wilcoxon's
 rank sum
 TJ-15 Placebo test

Total score for accessory 2.2[+ or -]1.9 1.6[+ or -]2.7 p = 0.079
symptoms of hypertension
Score for each accessory
 symptom of hypertension
 Irritability 0.4[+ or -]0.7 0.4[+ or -]0.9 p = 0.767
 Anxiety 0.3[+ or -]0.6 0.3[+ or -]0.8 p = 0.784
 Sleep disorder 0.5[+ or -]0.7 0.3[+ or -]1.1 p = 0.188
 Hot flushes 0.6[+ or -]0.8 0.3[+ or -]0.9 p = 0.028
 Facial suffusion 0.5[+ or -]0.7 0.3[+ or -]0.8 p = 0.037
 Total score for general 1.1[+ or -]2.1 0.5[+ or -]2.1 p = 0.017
symptoms
Score for each general
 symptom
 Headache/heavy headedness 0.3[+ or -]0.8 0.2[+ or -]1.0 p = 0.315
 Shoulder stiffness 0.3[+ or -]0.8 0.2[+ or -]0.8 p = 0.204
 Dizziness 0.1[+ or -]0.5 0.1[+ or -]0.5 p = 0.392
 Generalized weakness 0.2[+ or -]0.7 0.1[+ or -]0.7 p = 0.050

 Final evaluation
 Wilcoxon's
 rank sum
 TJ-15 Placebo test

Total score for accessory 3.1[+ or -]1.9 2.3[+ or -]2.5 p = 0.013
symptoms of hypertension
Score for each accessory
 symptom of hypertension
 Irritability 0.6[+ or -]0.8 0.5[+ or -]0.9 p = 0.522
 Anxiety 0.4[+ or -]0.7 0.3[+ or -]0.7 p = 0.436
 Sleep disorder 0.7[+ or -]0.8 0.5[+ or -]0.9 p = 0.353
 Hot flushes 0.7[+ or -]0.8 0.5[+ or -]1.0 p = 0.034
 Facial suffusion 0.7[+ or -]0.8 0.4[+ or -]0.8 p = 0.022
 Total score for general 1.8[+ or -]2.4 1.2[+ or -]2.4 p = 0.078
symptoms
Score for each general
 symptom
 Headache/heavy headedness 0.5[+ or -]0.9 0.4[+ or -]0.9 p = 0.382
 Shoulder stiffness 0.6[+ or -]1.0 0.4[+ or -]0.9 p = 0.100
 Dizziness 0.2[+ or -]0.5 0.1[+ or -]0.5 p = 0.119
 Generalized weakness 0.3[+ or -]0.8 0.3[+ or -]0.9 p = 0.413

Values are the mean[+ or -]SD.

Table 5. Total courses of accessory symptoms of hypertension and general
symptoms (evaluated by the investigator on the case)

 Slightly
 Improved improved Unchanged

(1) Outcome of accessory symptoms of hypertension (evaluation by the
 investigator)
Interim evaluation TJ-15 27 49 25
 Placebo 26 29 36
Overall evaluation TJ-15 48 44 11
 Placebo 38 37 22

(2) Outcome of general symptoms of hypertension (evaluation by the
 investigator)
Interim evaluation TJ-15 18 40 30
 Placebo 15 16 47
Overall evaluation TJ-15 31 38 20
 Placebo 25 34 23

 Aggravated Cochran-Mantel-Haenszel test

(1) Outcome of accessory symptoms of hypertension (evaluation by the
 investigator)
Interim evaluation TJ-15 2 p = 0.044
 Placebo 9
Overall evaluation TJ-15 0 p = 0.028
 Placebo 4

(2) Outcome of general symptoms of hypertension (evaluation by the
 investigator)
Interim evaluation TJ-15 6 p = 0.002
 Placebo 13
Overall evaluation TJ-15 5 p = 0.125
 Placebo 11

Table 6. Utility rating

 Very Moderately Slightly Not
 useful useful useful useful

Interim evaluation TJ-15 6 27 47 23
 Placebo 6 17 34 39
Final evaluation TJ-15 11 33 48 9
 Placebo 7 28 37 24

 Cochran-Mante-Haenszel
 Contraindicated test

Interim evaluation TJ-15 0 p = 0.005
 Placebo 4
Final evaluation TJ-15 1 p = 0.016
 Placebo 4

Table 7. Reduction of blood pressure and antihypertensive effect

(1) Reduction of blood pressure
 Wilcoxon's
 rank sum
 TJ-15 Placebo test

Systolic pressure (mmHg) 7.5[+ or -]9.9 6.6[+ or -]10.2 p = 0.946
Diastolic pressure (mmHg) 4.5[+ or -]6.7 3.8[+ or -]6.7 p = 0.787
Mean blood pressure (mmHg) 5.5[+ or -]7.0 4.8[+ or -]7.0 p = 0.945

(2) Antihypertensive effect
 Slightly Cochran-Mantel-
 Decreased decreased Unchanged Increased Haenszel test

TJ-15 16 27 58 2 p = 0.620
Placebo 10 33 51 6

Values are the mean[+ or -]SD.

Table 8. Overall safety rating

 No safety Slight safety Definite safety
 problems problems problems

Interim evaluation TJ-15 120 4 0
 Placebo 113 6 1
Final evaluation TJ-15 113 13 2
 Placebo 112 9 2

 Serious safety Cochran-Mantel-Haenszel
 Problems test

Interim evaluation TJ-15 0 p = 0.322
 Placebo 0
Final evaluation TJ-15 0 p = 0.480
 Placebo 0
COPYRIGHT 2006 Urban & Fischer Verlag
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2006 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Arakawa, K.; Saruta, T.; Abe, K.; Iimura, O.; Ishii, M.; Ogihara, T.; Hiwada, K.; Fukiyama, K.; Fuji
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Clinical report
Geographic Code:9JAPA
Date:Jan 1, 2006
Words:4803
Previous Article:Scientific Basis for Ayurvedic Therapies.
Next Article:Efficacy and tolerability of potato juice in dyspeptic patients: a pilot study.
Topics:


Related Articles
The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine growth retardation in preeclampsia rats induced by...
A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with...
Tsumura Elucidates That White Mulberry Extract May Help Prevent Hair Loss.
Does scientific evidence support the use of non-prescription supplements for treatment of acute menopausal symptoms such as hot flushes?
A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of...
Herbal remedies for anxiety--a systematic review of controlled clinical trials.
Tsumura to Release Chinese Herbal Medicine-based Revitalizer.
A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis.
Interaction between Shaoyao-Gancao-Tang and a laxative with respect to alteration of paeoniflorin metabolism by intestinal bacteria in rats.
New herbal leads for asthma management.

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters