Trial record 5 of 13 for:    "Stress cardiomyopathy"

Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by Second University of Naples.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Raffaele Marfella, Second University of Naples
ClinicalTrials.gov Identifier:
NCT01524861
First received: January 23, 2012
Last updated: January 30, 2012
Last verified: January 2012
  Purpose

Stress (tako-tsubo) cardiomyopathy (SC) is a rapidly reversible form of acute heart failure reported to be triggered by stressful events and associated with a distinctive left ventricular (LV) contraction pattern.

SC mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. sympathetic activity dysfunction appears to play a very important role in the pathophysiology of takotsubo cardiomyopathy.

In most cases, myocardial scintillography with 123Imetaiodobenzylguanidine (MIBG) showed altered captation of the radiotracer in several heart segments. In particular, the apical myocardium has poor sympathetic innervations and an uptake reduction in MIBG tracer.

A hypothesis for this finding could be that the intense discharge of adrenalin, acting on heart segment with different and abnormal innervation, may produce a transient heart failure characterized by a particular shape of the left ventricle.

While studies have shown that heterogeneous MIBG distribution, decreased MIBG uptake and increased norepinephrine content were completely prevented by α-lipoic acid or by L-acetyl carnitine administrations in diabetic cardiomyopathy, no studies have examined the effects of these therapies on tako-tsubo cardiomyopathy.

On this basis, the investigators study will evaluate whether the dysfunction of adrenergic cardiac innervation, evaluated by MIBG, persist after previous experience of transient stress-induced cardiac dysfunction. Moreover, the investigators will assess whether the medications that restore sympatho-vagal alterations in diabetic cardiomyopathy, such as α-lipoic acid and L-acetyl carnitine, will improve the adrenergic cardiac innervation, in patients with SC.


Condition Intervention Phase
Apical Ballooning Syndrome
Nervous System Diseases, Sympathetic
Drug: Placebo
Drug: alpha-lipoic acid
Drug: L-acetyl carnitine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Sympathetic Heart Innervation in Patients With Previous Experience of Transient Stress-induced Cardiomyopathy (Tako-Tsubo): Effects of α-lipoic Acid and L-acetyl Carnitine Therapies.

Resource links provided by NLM:


Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: Yes ]
    The improvement of adrenergic cardiac innervation as determined by quantitative MIBG


Secondary Outcome Measures:
  • Change from Baseline in the markers of inflammation at 6 and 12 months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: Yes ]
    Serum concentrations of IL-6 and IL-18 will be determined using a highly sensitive, quantitative sandwich enzyme assay. High-sensitivity TNF-α will assayed by immune-nephelometry. CRP will be determined using automated turbidimetry.

  • Change from Baseline in the markers of oxidative stress at 6 and 12 months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: Yes ]
    Nitrotyrosine plasma concentration, will be assayed by enzyme-linked immunosorbent assay.

  • Change from Baseline in the markers of myocardial damage at 6 and 12 months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: Yes ]
    Serum levels of Troponin I, miR-1, miR-133a, and miR-499 will be evaluated.

  • Change from Baseline in the markers of sympathetic tone at 6 and 12 months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: Yes ]
    Plasma levels of catecholamines and their metabolites will measured by HPLC; brain natriuretic peptide and neuropeptide Y will be measured by enzyme immunoassay.


Enrollment: 90
Study Start Date: December 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
30 subjects receive placebo (placebo group)
Drug: Placebo
a placebo tablet bis in die for 12 months
Experimental: alpha-lipoic acid
30 subjects receive alpha-lipoic acid, 400 mg/day per os bis in die (800 mg/day)(ALA group)
Drug: alpha-lipoic acid
alpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months
Experimental: L-acetil-carnitine
30 subjects receive L-acetyl carnitine, 500 mg per os bis in die (1000 mg/day) (LAC group)
Drug: L-acetyl carnitine
L-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months

Detailed Description:

Study design Each patient will be assessed with history and physical examination, 12-lead ECG, serum troponin, coronary arteriography, and LV angiogram (an average of 6 hours after admission to the hospital), with echocardiography and 123Imetaiodobenzylguanidine (MIBG) myocardial scintillography. All patients were admitted to the cardiac care unit after coronary angiography. Currently recommended treatments for acute coronary syndromes (ACS), with therapy directed at relieving myocardial ischemia and preventing thrombotic complications, were provided to all patients. For each patient, the Charlson score index, 8 which represents the most studied and evaluated comorbidity index, will be calculated. At discharge, surviving patients with established SC will be managed and followed for 12 month after the event, as outpatients. At discharge, the surviving patients will be randomly assigned to alpha-lipoic acid 800 mg/day treatment (ALA group), or L-acetyl carnitine 1000 mg/day treatment (LAC group) or placebo (control group). With regard to the full medical therapy, the protocol stated that the use of concomitant treatment should be uniform, between the groups, and according to evidence-based international guidelines for ACS in all patients. Following discharge, patients were asked to return to our outpatient clinic for follow-up evaluation at 6 and 12 months after the initial event of SC.

Coronary Angiography Coronary angiograms at baseline, immediately after percutaneous coronary intervention (PCI) will be performed in at least 2 orthogonal views after intracoronary nitroglycerin. The analyses of all angiographic data will be performed by operators who were unaware of the study groups (Toshiba, Infinix CS-i).

Echocardiography LV function will be evaluated in all patients by two-dimensional echocardiography at admission, 6 and 12 months after the discharge.

MIBG imaging. MIBG imaging will be performed in all patients shortly after admission and at 6 and 12 months after the discharge. MIBG will be performed with a The standard protocol for 123I-MIBG cardiac imaging requires that drugs that interfere with 123I-MIBG uptake be withheld. A comprehensive listing of prescription and over-the-counter drugs that interfere with 123I-MIBG biodistribution, and the time for which they should be withheld, has been published . Thyroid uptake of unbound 123I is blocked with 500 mg of potassium perchlorate given orally 30 min before 123I-MIBG injection. Between 148 MBq and 370 MBq of 123I-MIBG are injected intravenously at rest. Both planar and SPECT images are acquired 15 min after injection (early) and 4 h after injection (delayed). A dual head gammacamera (ECAM Siemens, Erlangen - Germany) equipped with a low-energy - high resolution collimator was used. A 20% window is usually centered over the 159-keV photopeak of 123I for imaging. Anterior planar images of the chest are acquired using a 256 x 256 matrix. single photon emission computed tomography (SPECT) images are acquired using a 64 x 64 matrix over 180°, from the right anterior oblique position to the left posterior oblique position. Planar imaging allows for global assessment of cardiac innervation, whereas SPECT allows for regional evaluation. Quantitative evaluations will be performed with a standard protocol previously described.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • acute onset of a cardiovascular event, usually associated with substernal chest pain, initially regarded as ST-segment elevation myocardial infarction/evolving coronary syndrome;
  • systolic dysfunction, predominantly characterized by akinesia/hypokinesia of the mid-to-distal portion of the LV chamber, with hypercontractile basal LV;

Exclusion Criteria:

  • presence, by angiography, of significant atherosclerotic luminal narrowing in each of the 3 epicardial coronary arteries (0 to < 25%) (- presence of pheochromocytoma, myocarditis, or hypertrophic cardiomyopathy.
  • coexisting conditions that limited life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524861

Locations
Italy
Dept Geriatric and Metabolic diseases SUN
Naples, Italy
Sponsors and Collaborators
Second University of Naples
Investigators
Principal Investigator: Raffaele Marfella, MD, PhD Second University of Naples
Principal Investigator: Raffaele Marfella, MD, PhD Dept Geriatric and Metabolic diseases SUN, Naples, Italy
  More Information

No publications provided

Responsible Party: Raffaele Marfella, Assistant Professor of Internal Medicine, Second University of Naples
ClinicalTrials.gov Identifier: NCT01524861     History of Changes
Other Study ID Numbers: IT 278354
Study First Received: January 23, 2012
Last Updated: January 30, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by Second University of Naples:
Tako-Tsubo
Sympathetic heart innervation
MIBG
Alpha-lipoic acid
L-acetyl carnitine

Additional relevant MeSH terms:
Takotsubo Cardiomyopathy
Nervous System Diseases
Autonomic Nervous System Diseases
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction, Left
Ventricular Dysfunction
Acetylcarnitine
Carnitine
Thioctic Acid
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 24, 2014