UMIN-CTR Clinical Trial

Public title

Long term effect of Japanese Kampo formula gosyajinkigan in diabetic
complication; randomized open-labeled trial.

Acronym

Long term effect of Japanese Kampo formula gosyajinkigan in diabetic
complication; randomized open-labeled trial.

Scientific Title

Long term effect of Japanese Kampo formula gosyajinkigan in diabetic
complication; randomized open-labeled trial.

Scientific Title:Acronym

Long term effect of Japanese Kampo formula gosyajinkigan in diabetic
complication; randomized open-labeled trial.

Region

Japan

Condition

Diabetes mellitus

Classification by specialty

Medicine in general	Endocrinology and Metabolism	Geriatrics
Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To determine whether a Kampo formula
goshajinkigan (TJ107) would reduce the rate of cardiovascular events, microvascular complications and any laboratory abnormalities as compared with control group without this kampo formulation in middle-aged and older people with diabetes mellitus.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

The prespecified primary endpoints were the first occurrence of nonfatal myocardial infarction or nonfatal stroke or one or more upstaging of diabetic nephropathy(DN) or retinopathy(DR).

Key secondary outcomes

body weight, blood
pressure, fasting blood glucose, glycated hemoglobin, serum insulin (c-peptide reactivity on insulin user) , total cholesterol, triglycelide, high density lipoprotein, serum creatinin, urea
nitrogen and diabetic neuropathy

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Numbered container method

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Regular treatment plus Kampo formulation goshajinkigan
(TJ107) every 3 preprandial for 5 years

Interventions/Control_2

Regular treatment

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

40

years-old

<=

Age-upper limit

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

volunteers who had type 2 diabetes mellitus and a glycated hemoglobin level
of 6.5% or more and who either were between the ages of 40 and 75 years without neither macroalbuminuria nor serum creatinin level of more than 1.3 mg per deciliter nor diabetic retinopathy over pre-proliferative retinopathy.

Key exclusion criteria

past macrovascular event including stroke, myocardial infarction, angina pectoris, foot gangrene, atheroscrerotic obstruction and other serious complication, taking other kampo formulation, drug allergy to TJ107, pregnant or lactating women and unwillingness to enter the study.
Additional exclusion criteria were a body mass index of ≥30 kg/m2; 2 or more digestive system symptoms (e.g., gastrointestinal weakness, anorexia, nausea, and diarrhea); and 3 or more symptoms or activities indicative of sensitivity to heat, including a preference for dressing lightly, sweating upwards from the neck, a liking for cold water, a flushed face, congestion of the eyeballs, and a tendency towards high body temperatures (not less than 36.7 degrees cercius).

Target sample size

1500

Name of lead principal investigator

1st name
Middle name
Last name	Kenji Watanabe

Organization

School of medicine, Keio University

Division name

centor for Kampo medicine

Zip code

Address

Shinanomachi, Shinjuku, Tokyo, Japan

TEL

03-5366-3824

Email

Name of contact person

1st name
Middle name
Last name	Kenji Watanabe

Organization

School of medicine, Keio University

Division name

centor for Kampo medicine

Zip code

Address

Shinanomachi, Shinjuku, Tokyo, Japan

TEL

03-5366-3824

Homepage URL

Email

watanabekenji@a6.keio.jp

Institute

Keio University School of Medicine

Institute

Department

Personal name

Organization

the Ministry of Health, Labor and Welfare Research Council of Japan

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Tsumura Co.(Tokyo, Japan) manufactures of TJ107

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

慶應義塾大学病院（東京都）

Date of disclosure of the study information

2013

Year

05

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Patients

A total of 117 men and women with a median age of 61 years (range, 41 to 76 years) and a median glycated hemoglobin level of 7.5% (range, 6.5 to 12.2%) were randomly assigned to either the TJ107 group or the control group. Approximately 40% of both patient cohorts were women. The key baseline characteristics were similar in the 2 study groups. The mean duration of follow-up was 28 months for the TJ107 group and 15 months for the control group. The trial was stopped when the national funding stopped, although significantly more volunteers were to be included in the trial.

Use of Glucose-Lowering Therapy and Other Treatments

During the follow-up period, the use of most classes of oral hypoglycemic drugs and of insulin was the same in the 2 groups. In addition, the use of blood pressure-lowering, lipid-modifying, and antiplatelet treatments was similar between the 2 groups during the follow-up period. However, the combined use of several drugs occurred at a much lower frequency than our general experience, so that patients may not have accurately reported medication use in all cases.

Effects on Primary Outcomes

A total of 43 participants had a microvascular event: 40.2% in the TJ107 group and 39.1% in the control group (P = 0.752, Figure 3). No macrovascular event occurred in either group.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2000

Year

03

Month

01

Day

Date of IRB

Anticipated trial start date

2000

Year

03

Month

01

Day

Last follow-up date

2007

Year

08

Month

31

Day

Date of closure to data entry

2007

Year

08

Month

31

Day

Date trial data considered complete

2007

Year

08

Month

31

Day

Date analysis concluded

2013

Year

03

Month

31

Day

Other related information

Effects on Secondary Outcomes

Stable median levels of glycated hemoglobin of 7.8% (interquartile range, 6.4 to 11.5) and 7.9% (interquartile range, 6.7 to 13.5), were maintained in the TJ107 and control groups, respectively, throughout the follow-up period. According to an exploratory examination, the glycated hemoglobin of the TJ107 group decreased significantly in the 60th month as compared to the control group, but not at the final point. Fasting plasma glucose also decreased significantly beginning at the 36th month relative to baseline, while no significant changes were observed in the control group. No significant differences were observed in terms of insulin doses or oral anti-diabetic medications.

The progression of the grade of the ankle reflex was significantly more frequent in the control group. Other outcomes, including body mass index and laboratory test results, showed no significant differences.

Most patients had no subjective symptoms through the trial period. An analysis of only the patients who had a change in subjective symptoms was performed, in addition to an analysis of the entire set of patients. For the patients who experienced a change in symptoms, the occurrence of constipation and diarrhea was significantly improved in the TJ107 group. For the entire set of patients, no significant changes occurred for any of the issues addressed in the questions. There was no dropout due to the side effects of TJ107.

Registered date

2013

Year

04

Month

26

Day

Last modified on

2013

Year

04

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010180