Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pathogenesis of Acute Stress Induced (Tako-tsubo) Cardiomyopathy: Energy Shut-Down or Intense Inflammation? (TERRIFIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02897739
Recruitment Status : Completed
First Posted : September 13, 2016
Last Update Posted : May 8, 2019
Sponsor:
Collaborator:
NHS Grampian
Information provided by (Responsible Party):
University of Aberdeen

Brief Summary:
Tako Tsubo Cardiomyopathy (TTC), also known as "Broken Heart Syndrome", is a disorder of the heart that occurs most commonly in women (although it occasionally occurs in men) and is usually related to a stressful event. Symptoms are often similar to a heart attack, and include chest pain and shortness of breath. Although Tako Tsubo Cardiomyopathy is not a new medical condition, it has not been widely recognised until the last decade. Currently the investigators don't have an exact understanding of how or why the heart is affected in this way, and so the investigators are conducting a study to help understand what causes Tako Tsubo Cardiomyopathy.

Condition or disease Intervention/treatment
Tako-tsubo Cardiomyopathy Procedure: Magnetic resonance imaging Biological: Acute Inflammatory Activation study Radiation: PET CT Behavioral: Psychological assessment

Detailed Description:

The investigators aim to study the reciprocal modulation of fatty acids and glucose metabolism in the Tako Tsubo Cardiomyopathy physiology, in both humans and an animal model, and to investigate which metabolic pathway is preferentially adopted by acute Tako Tsubo Cardiomyopathy myocytes during this severe functional shut down with largely preserved variability. The human model will be used to determine the preferential stimulated uptake of glucose/fatty acids under optimal metabolic conditions for each (hyperinsulineamic euglycemic clamp for 18F-Fludeoxyglucose (18F-FDG) and fasting for 14Fluorine-18Fluoro-6-Thia-Heptadecanoic Acid (18F-FTHA cardiac Positron Emission Tomography)). In the rat model the investigators will examine both the metabolic tracer uptake (using micro Positron Emission Tomography-Computed Tomography) as well as the downstream modulation of the two metabolic pathways (transcriptional regulators, mitochondrial respiration, expression of the uncoupling proteins, levels of Adenosine Triphosphate generation and reactive oxygen species production).

The investigators aim to test the hypothesis that inflammation plays a pivotal role in the pathophysiology of this condition by further exploring: 1) In the rat model define time course, extent and subtypes of cellular infiltrate, 2) In the rat model of Tako Tsubo Cardiomyopathy, demonstrate the presence of inflammatory macrophages using in-vivo Ultrasmall Superparamagnetic Iron Oxide-cardiac magnetic resonance imaging and whether this relates to numbers and types of macrophages present as determined by immunohistochemical analysis, 3) In clinical patients, define the time course of specific peripheral blood monocyte subsets and the serum levels of inflammatory cytokines versus matched controls and 4) In clinical patients, establish the compartmentalisation of tissue macrophages in the left ventricle its time course resolution using Ultrasmall Superparamagnetic Iron Oxide-enhanced cardiac magnetic resonance.

The investigators will assess the psycho-emotional factors involved in Tako Tsubo Cardiomyopathy given that in the majority of cases intense emotional trauma is immediately preceding onset.


Layout table for study information
Study Type : Observational [Patient Registry]
Actual Enrollment : 77 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 4 Months
Official Title: Pathogenesis of Acute Stress Induced (Tako-tsubo) Cardiomyopathy: Energy Shut-Down or Intense Inflammation? The TERRIFIC Study
Actual Study Start Date : August 2015
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiomyopathy

Group/Cohort Intervention/treatment
TTC Patients
Patients diagnosed with Tako-tsubo cardiomyopathy.
Procedure: Magnetic resonance imaging
Cardiac MRI and short MRI following USPIO infusion

Biological: Acute Inflammatory Activation study
Blood sampling for exploration of type and level of inflammatory response

Radiation: PET CT
PET study for metabolic pathway study

Behavioral: Psychological assessment
Assessment by a psychologist

Health Volunteers
Participants who have normal hearts.
Procedure: Magnetic resonance imaging
Cardiac MRI and short MRI following USPIO infusion

Biological: Acute Inflammatory Activation study
Blood sampling for exploration of type and level of inflammatory response

Radiation: PET CT
PET study for metabolic pathway study

Behavioral: Psychological assessment
Assessment by a psychologist




Primary Outcome Measures :
  1. Cardiac Inflammation as measured by Cardiac Magnetic Resonance Imaging [ Time Frame: Three years ]
    As measured by cardiac MRI


Secondary Outcome Measures :
  1. Evidence of psycho-emotional factors following intense physical or emotional stress as measured by Hospital Anxiety and Depression Scale [ Time Frame: Three years ]
    As measured by psychiatric interview

  2. Evidence of alterations of the metabolism of myocardium by Cardiac Positron Emission Tomography [ Time Frame: Three years ]
    As measured by PET CT

  3. Systemic Inflammation as measured by inflammatory markers [ Time Frame: Three years ]
    As measured by inflammatory markers


Biospecimen Retention:   Samples With DNA
EDTA blood samples, EDTA Plasma and Serum to be retained.


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients who have been diagnosed with Tako-tsubo Cardiomyopathy Healthy volunteers
Criteria

Inclusion Criteria:

  • All patients diagnosed with TTC in the past 12 days, able to give consent and who have not lost capacity of consent between the time of diagnosis (usually made at coronary catheterisation, for which they are consented clinically) and time of being approached for inclusion in the study.
  • Age and gender matched healthy controls willing to participate and able to give consent.

Exclusion Criteria:

  • Unwillingness to participate
  • Patients with contraindications to MR scanning
  • Pregnant or breast-feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02897739


Locations
Layout table for location information
United Kingdom
Cardiac Research Office
Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZD
Sponsors and Collaborators
University of Aberdeen
NHS Grampian
Investigators
Layout table for investigator information
Principal Investigator: Dana Dawson, MD, MRCP University of Aberdeen

Additional Information:

Publications:
Chen X, Lee G, Maher BS, Fanous AH, Chen J, Zhao Z, Guo A, van den Oord E, Sullivan PF, Shi J, Levinson DF, Gejman PV, Sanders A, Duan J, Owen MJ, Craddock NJ, O'Donovan MC, Blackman J, Lewis D, Kirov GK, Qin W, Schwab S, Wildenauer D, Chowdari K, Nimgaonkar V, Straub RE, Weinberger DR, O'Neill FA, Walsh D, Bronstein M, Darvasi A, Lencz T, Malhotra AK, Rujescu D, Giegling I, Werge T, Hansen T, Ingason A, Nöethen MM, Rietschel M, Cichon S, Djurovic S, Andreassen OA, Cantor RM, Ophoff R, Corvin A, Morris DW, Gill M, Pato CN, Pato MT, Macedo A, Gurling HM, McQuillin A, Pimm J, Hultman C, Lichtenstein P, Sklar P, Purcell SM, Scolnick E, St Clair D, Blackwood DH, Kendler KS; GROUP investigators; International Schizophrenia Consortium. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia. Mol Psychiatry. 2011 Nov;16(11):1117-29. doi: 10.1038/mp.2010.96. Epub 2010 Sep 14.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Aberdeen
ClinicalTrials.gov Identifier: NCT02897739     History of Changes
Other Study ID Numbers: 14/NS/1068
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: May 8, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiomyopathies
Takotsubo Cardiomyopathy
Inflammation
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction, Left
Ventricular Dysfunction