UMIN-CTR Clinical Trial

Public title

Role of autonomic nervous system and adrenoceptor gene mutation in Takotsubo Cardiomyopathy

Acronym

Role of autonomic nervous system and adrenoceptor gene mutation in Takotsubo Cardiomyopathy

Scientific Title

Role of autonomic nervous system and adrenoceptor gene mutation in Takotsubo Cardiomyopathy

Scientific Title:Acronym

Role of autonomic nervous system and adrenoceptor gene mutation in Takotsubo Cardiomyopathy

Region

Japan

Condition

Takotsubo cardiomyopathy

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

Takotsubo cardiomyopathy (TCM), also called broken heart syndrome, is typically reported in the setting of emotional and/or physiological stress. The exact pathophysiology of TCM is poorly understood. Nevertheless altered autonomic nervous regulation, and in consequence, over excretion of catecholamines may play an important role in triggering the syndrome.

Basic objectives2

Others

Basic objectives -Others

We will determine if TCM patients have an excess sympathetic nerve activity and/or overstated sympathetic response to stress compared to healthy subjects. Also we will assess the susceptibility of having an exaggerated sympathetic response to stress upon polymorphisms of the adrenoceptors.

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

The primary outcome is plasma norepinephrine and epinephrine during the stress test between TCM and healthy subjects.

Key secondary outcomes

The secondly outcome is blood pressure, heart rate, indexes of autonomic function test and genetic polymorphisms of adrenoceptors between TCM and control subjects.

Study type

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Prevention

Type of intervention

Other

Interventions/Control_1

We will assess the stress reaction after we perform the standard autonomic function test of participants.
All the medications which might affect the autonomic nervous system were withheld for at least five times the elimination half-life before the studies. Continuous blood pressure (BP) and heart rate (HR) measurements were obtained using an automated oscillometric sphygmomanometer and tonometry (BP-608 Evolution II, Omron Colin Corporation). An antecubital vein will be cannulated for blood sampling of plasma catecholamines and cortisol before and after stress loading tests, namely speech test and mental calculation test. Continuous HR and BP during the tests will be recorded. The order of mental calculation test and speech test will be randomized to avoid order effect.
Subjects will be asked to begin with 1000 and count backward by 17 as much as they can for 3 minutes (eg. 1000-17=983, 983-17=966, ...).
The theme of the speech test will be chosen by each subjects from the following; self introduction, a funny story of recent or a touching tale. They will speech in front of the medical profession(s) for 3 minutes.

Interventions/Control_2

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

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

A. Definition criteria of TCM
1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular midsegments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always present.
2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.
3. New electrocardiographic abnormal-
ities (either ST-segment elevation and/or T-wave inversion) or modest elevation of cardiac troponin.
4. Absence of:recent significant head trauma, intracranial bleeding, pheochromocytoma, myocarditis, hypertrophic cardiomyopathy.

B. Subjects inclusion criteria
1. Age >= 20 years old.
2. TCM patietns: History of TCM more than the prior 3 weeks with well-preserved general condition.
3. Healthy subjects: Matched by a comparable age and sex of TCM patients.

Key exclusion criteria

1. Patients who have uncontrolled cardiovascular diseases such as congestive heart failure, ischemic heart disease, hypertension, arrhythmia
2. Patients who have uncontrolled diabetes meltis
3. Pregnant or lactating women
4. Patients who have overt concomitant disease
5. Patients who are not eligible for this study by study doctors

Target sample size

80

Name of lead principal investigator

1st name
Middle name
Last name	Hiroshi Sakura

Organization

Tokyo Women's Medical University, East Medical Center

Division name

Department of Medicine

Zip code

Address

2-1-10 Nishiogu, Arakawa, Tokyo, 116-8567

TEL

03-3810-1111

Email

sakuragm@dnh.twmu.ac.jp

Name of contact person

1st name
Middle name
Last name	Kyoko Sato

Organization

Tokyo Women's Medical University, East Medical Center

Division name

Department of Medicine

Zip code

Address

2-1-10 Nishiogu, Arakawa, Tokyo, 116-8567

TEL

03-3810-1111

Homepage URL

Email

satokgm@dnh.twmu.ac.jp

Institute

Tokyo Women's Medical University

Institute

Department

Personal name

Organization

Grant-in-Aid for Scientific Research (C)

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Tokai University

Name of secondary funder(s)

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

東京女子医科大学東医療センター（東京都）

Date of disclosure of the study information

2015

Year

03

Month

31

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

Open public recruiting

Date of protocol fixation

2014

Year

12

Month

03

Day

Date of IRB

Anticipated trial start date

2015

Year

03

Month

31

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

03

Month

31

Day

Last modified on

2015

Year

03

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019374