Apical Ballooning SyndromePhase 4NCT01524861
Sympathetic Heart Innervation in Patients With Tako-Tsubo Cardiomyopathy
A Phase 4 study testing alpha-lipoic acid and L-acetyl carnitine in people with Apical Ballooning Syndrome and Nervous System Diseases, Sympathetic, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Apical Ballooning Syndrome, Nervous System Diseases, Sympathetic
- What is being tested?
- alpha-lipoic acid and L-acetyl carnitine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2011to Jan 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read more
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.
Read the 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.
- Being tested
- Placebo, alpha-lipoic acid, L-acetyl carnitine
- Keywords
- Tako-Tsubo, Sympathetic heart innervation, MIBG, Alpha-lipoic acid, L-acetyl carnitine
- Medical subject headings
- Takotsubo Cardiomyopathy, Autonomic Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
a placebo tablet bis in die for 12 months
alpha-lipoic acidDrug
alpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months
L-acetyl carnitineDrug
L-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 30 subjects receive placebo (placebo group) Receives: 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) Receives: 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) Receives: Drug: L-acetyl carnitine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months
The improvement of adrenergic cardiac innervation as determined by quantitative MIBG
Measured: 0, 6 and 12 months
Secondary outcomes (4)
Change from Baseline in the markers of inflammation at 6 and 12 months
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.
Measured: 0, 6 and 12 months
Change from Baseline in the markers of oxidative stress at 6 and 12 months
Nitrotyrosine plasma concentration, will be assayed by enzyme-linked immunosorbent assay.
Measured: 0, 6 and 12 months
Change from Baseline in the markers of myocardial damage at 6 and 12 months
Serum levels of Troponin I, miR-1, miR-133a, and miR-499 will be evaluated.
Measured: 0, 6 and 12 months
Change from Baseline in the markers of sympathetic tone at 6 and 12 months
Plasma levels of catecholamines and their metabolites will measured by HPLC; brain natriuretic peptide and neuropeptide Y will be measured by enzyme immunoassay.
Measured: 0, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2012 (estimated)
- Study startDec 2011
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Apical Ballooning SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raffaele Marfella, University of Campania Luigi Vanvitelli
- Investigators
- Raffaele Marfella, MD, PhD, Principal investigator, University of Campania Luigi VanvitelliRaffaele Marfella, MD, PhD, Principal investigator, Dept Geriatric and Metabolic diseases SUN, Naples, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01524861
- Sponsor's protocol ID
- IT 278354
- Status last verified
- Jan 2016
- First submitted
- 23 Jan 2012
- Last updated
- 27 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01524861
- Acronym / sponsor ID
- IT 278354
- Keywords
- Tako-Tsubo, Sympathetic heart innervation, MIBG, Alpha-lipoic acid, L-acetyl carnitine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 2 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo30 subjects receive placebo (placebo group) |
| alpha-lipoic acid | Experimental | Drug: alpha-lipoic acid30 subjects receive alpha-lipoic acid, 400 mg/day per os bis in die (800 mg/day)(ALA group) |
| L-acetil-carnitine | Experimental | Drug: L-acetyl carnitine30 subjects receive L-acetyl carnitine, 500 mg per os bis in die (1000 mg/day) (LAC group) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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;
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placeboa placebo tablet bis in die for 12 months | Drug | Placebo |
| alpha-lipoic acidalpha-lipoic, tablets of acid 400 mg bis in die (800 mg/day), for 12 months | Drug | alpha-lipoic acid |
| L-acetyl carnitineL-acetyl carnitine tablets, 500 mg bis in die (1000 mg/day), for 12 months | Drug | L-acetil-carnitine |
Primary outcome
Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months
Time frame: 0, 6 and 12 months
The improvement of adrenergic cardiac innervation as determined by quantitative MIBG
4 secondary outcomes
Change from Baseline in the markers of inflammation at 6 and 12 months
Time frame: 0, 6 and 12 months
Change from Baseline in the markers of oxidative stress at 6 and 12 months
Time frame: 0, 6 and 12 months
Change from Baseline in the markers of myocardial damage at 6 and 12 months
Time frame: 0, 6 and 12 months
Change from Baseline in the markers of sympathetic tone at 6 and 12 months
Time frame: 0, 6 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raffaele Marfella, MD, PhD principal investigator
University of Campania Luigi Vanvitelli
Raffaele Marfella, MD, PhD principal investigator
Dept Geriatric and Metabolic diseases SUN, Naples, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing alpha-lipoic acid and L-acetyl carnitine in people with Apical Ballooning Syndrome and Nervous System Diseases, Sympathetic, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in Adrenergic cardiac innervation at 6 and 12 months (time frame: 0, 6 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2016.