Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy

NCT01524861 | Completed Phase 4 DMC

• 1 other identifier: IT 278354
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Apical Ballooning Syndrome; Nervous System Diseases, Sympathetic

Keywords

Tako-Tsubo; Sympathetic heart innervation; MIBG; Alpha-lipoic acid; L-acetyl carnitine

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months

  The improvement of adrenergic cardiac innervation as determined by quantitative MIBG

  0, 6 and 12 months

Secondary Outcomes (4)

• Change from Baseline in the markers of inflammation at 6 and 12 months

  0, 6 and 12 months

• Change from Baseline in the markers of oxidative stress at 6 and 12 months

  0, 6 and 12 months

• Change from Baseline in the markers of myocardial damage at 6 and 12 months

  0, 6 and 12 months

• Change from Baseline in the markers of sympathetic tone at 6 and 12 months

  0, 6 and 12 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

30 subjects receive placebo (placebo group)

Drug: Placebo

alpha-lipoic acid

EXPERIMENTAL

30 subjects receive alpha-lipoic acid, 400 mg/day per os bis in die (800 mg/day)(ALA group)

Drug: alpha-lipoic acid

L-acetil-carnitine

EXPERIMENTAL

30 subjects receive L-acetyl carnitine, 500 mg per os bis in die (1000 mg/day) (LAC group)

Drug: L-acetyl carnitine

Interventions

Placebo DRUG

a placebo tablet bis in die for 12 months

Placebo

alpha-lipoic acid DRUG

alpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months

alpha-lipoic acid

L-acetyl carnitine DRUG

L-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months

L-acetil-carnitine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (1)

Dept Geriatric and Metabolic diseases SUN

Naples, Italy

Location

MeSH Terms

Conditions

Takotsubo Cardiomyopathy; Autonomic Nervous System Diseases

Interventions

Thioctic Acid; Acetylcarnitine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Carnitine; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines

Study Officials

• Raffaele Marfella, MD, PhD

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

• Raffaele Marfella, MD, PhD

  Dept Geriatric and Metabolic diseases SUN, Naples, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Study Record Dates

• First Submitted: January 23, 2012
• First Posted: February 2, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: January 27, 2016

Record last verified: 2016-01

Locations

IT (1)