- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04467411
Randomised Controlled Study of Physical Exercise Intervention in Breast Cancer Patients at Risk of Anthracycline-induced Cardiomyopathy: The EMBRACE Study (EMBRACE)
December 7, 2023 updated by: University of Aberdeen
Randomised Controlled Study of Physical Exercise Intervention in Breast Cancer Patients at Risk of Anthracycline-induced Cardiomyopathy:The EMBRACE Study
Cardiomyopathy is a condition that affects the heart muscle, whereby it becomes enlarged, thick or rigid.
When the heart muscle becomes involved, it affects the pumping action of the heart.
This condition can affect as many as 10% of all patients after undergoing anthracycline cancer drug therapy and unfortunately carries the worst prognosis of all cardiomyopathies.
To date, there is no effective intervention that will prevent a patient from developing this condition.
The research conducted will look to see if an energy imbalance in the heart predates the onset of detrimental changes to the pumping function of the heart, if this is detected then we can act earlier to prevent the pumping function deteriorating.
Study Overview
Status
Active, not recruiting
Conditions
Detailed Description
There is emerging cellular and experimental evidence that cardiac energetic status is reduced after anthracycline treatment, however, this has not been tested in the human heart.
The researchers hypothesize that cardiac energetic status is reduced in the human heart after administration of anthracycline therapy in breast cancer patients, inline with the evidence available from all other types of cardiomyopathies.
The researchers propose to use in vivo 31Phosphorus cardiac spectroscopy to measure the cardiac energetic status at the beginning and at the end of the cycles of chemotherapy in the hearts of breast cancer patients who are administered epirubicin (the most modern anthracycline to date) and compare this with the cardiac energetic status of age and gender matched healthy controls.
Further, the researchers wish to explore if the myopathy-induced effect of anthracyclines extends to the skeletal muscle as well, by examining skeletal muscle biopsies in these patients.
Study Type
Observational
Enrollment (Estimated)
12
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Maheshi Gunasekara, MD
- Phone Number: 01224559573
- Email: maheshi.gunasekara1@abdn.ac.uk
Study Contact Backup
- Name: Amelia Rudd, MSc
- Phone Number: 01467642401 01224559573
- Email: a.e.rudd@abdn.ac.uk
Study Locations
-
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Aberdeenshire
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Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZD
- Cardiovascular Research Facility
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Sampling Method
Probability Sample
Study Population
Healthy volunteers and patients diagnosed with breast cancer who have been scheduled for the first cycle of anthracycline therapy.
Description
Inclusion Criteria:
- A patient who has been diagnosed with breast cancer and has been scheduled for a first cycle of anthracycline therapy.
- Participant who is willing and able to give informed consent for participation in the study.
- Healthy (gender and age matched) volunteers willing to give informed consent for participation in the study.
Exclusion Criteria:
- Contraindication to magnetic resonance scanning such as an implantable cardiac device.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Breast Cancer Group
|
Healthy Volunteer
Healthy Volunteer Group
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cardiac Energetics
Time Frame: At baseline
|
Cardiac MRI and MRS
|
At baseline
|
Cardiac Energetics
Time Frame: Through study completion, up to sixteen weeks
|
Cardiac MRI and MRS
|
Through study completion, up to sixteen weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cardiac Imaging
Time Frame: At baseline
|
Echocardiography
|
At baseline
|
Cardiac Imaging
Time Frame: Through study completion, up to sixteen weeks
|
Echocardiography
|
Through study completion, up to sixteen weeks
|
Blood Biomarkers
Time Frame: At baseline
|
BNP and Troponins
|
At baseline
|
Blood Biomarkers
Time Frame: Through study completion, up to sixteen weeks
|
BNP and Troponins
|
Through study completion, up to sixteen weeks
|
Histology
Time Frame: At baseline
|
Histology of skeletal muscle biopsies
|
At baseline
|
Histology
Time Frame: Through study completion, up to sixteen weeks
|
Histology of skeletal muscle biopsies
|
Through study completion, up to sixteen weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Dana Dawson, MD, University of Aberdeen
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- O'Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Pina IL; HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1439-50. doi: 10.1001/jama.2009.454.
- Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL; American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409-26. doi: 10.1249/MSS.0b013e3181e0c112. Erratum In: Med Sci Sports Exerc. 2011 Jan;43(1):195.
- Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002 Mar 14;346(11):793-801. doi: 10.1056/NEJMoa011858.
- Jones LW, Haykowsky MJ, Swartz JJ, Douglas PS, Mackey JR. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007 Oct 9;50(15):1435-41. doi: 10.1016/j.jacc.2007.06.037. Epub 2007 Sep 24.
- Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, Baughman KL, Kasper EK. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000 Apr 13;342(15):1077-84. doi: 10.1056/NEJM200004133421502.
- Kitzman DW, Brubaker PH, Herrington DM, Morgan TM, Stewart KP, Hundley WG, Abdelhamed A, Haykowsky MJ. Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. J Am Coll Cardiol. 2013 Aug 13;62(7):584-92. doi: 10.1016/j.jacc.2013.04.033. Epub 2013 May 9.
- Coats AJ, Adamopoulos S, Radaelli A, McCance A, Meyer TE, Bernardi L, Solda PL, Davey P, Ormerod O, Forfar C, et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation. 1992 Jun;85(6):2119-31. doi: 10.1161/01.cir.85.6.2119.
- Hegde SM, Claggett B, Shah AM, Lewis EF, Anand I, Shah SJ, Sweitzer NK, Fang JC, Pitt B, Pfeffer MA, Solomon SD. Physical Activity and Prognosis in the TOPCAT Trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). Circulation. 2017 Sep 12;136(11):982-992. doi: 10.1161/CIRCULATIONAHA.117.028002. Epub 2017 Jun 21.
- Pandey A, Garg S, Khunger M, Darden D, Ayers C, Kumbhani DJ, Mayo HG, de Lemos JA, Berry JD. Dose-Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis. Circulation. 2015 Nov 10;132(19):1786-94. doi: 10.1161/CIRCULATIONAHA.115.015853. Epub 2015 Oct 5.
- Barwell ND, Malkova D, Moran CN, Cleland SJ, Packard CJ, Zammit VA, Gill JM. Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes. Diabetologia. 2008 Oct;51(10):1912-9. doi: 10.1007/s00125-008-1097-6. Epub 2008 Jul 29.
- Dawson DK, Neil CJ, Henning A, Cameron D, Jagpal B, Bruce M, Horowitz J, Frenneaux MP. Tako-Tsubo Cardiomyopathy: A Heart Stressed Out of Energy? JACC Cardiovasc Imaging. 2015 Aug;8(8):985-7. doi: 10.1016/j.jcmg.2014.10.004. Epub 2014 Nov 1. No abstract available.
- Jones LW, Liang Y, Pituskin EN, Battaglini CL, Scott JM, Hornsby WE, Haykowsky M. Effect of exercise training on peak oxygen consumption in patients with cancer: a meta-analysis. Oncologist. 2011;16(1):112-20. doi: 10.1634/theoncologist.2010-0197. Epub 2011 Jan 6. Erratum In: Oncologist. 2011;16(2):260.
- Zamorano JL, Lancellotti P, Rodriguez Munoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM; ESC Scientific Document Group. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016 Sep 21;37(36):2768-2801. doi: 10.1093/eurheartj/ehw211. Epub 2016 Aug 26. No abstract available. Erratum In: Eur Heart J. 2016 Dec 24;:
- Maslov MY, Chacko VP, Hirsch GA, Akki A, Leppo MK, Steenbergen C, Weiss RG. Reduced in vivo high-energy phosphates precede adriamycin-induced cardiac dysfunction. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H332-7. doi: 10.1152/ajpheart.00727.2009. Epub 2010 May 21.
- Menna P, Salvatorelli E, Minotti G. Anthracycline degradation in cardiomyocytes: a journey to oxidative survival. Chem Res Toxicol. 2010 Jan;23(1):6-10. doi: 10.1021/tx9003424.
- Higgins AY, O'Halloran TD, Chang JD. Chemotherapy-induced cardiomyopathy. Heart Fail Rev. 2015 Nov;20(6):721-30. doi: 10.1007/s10741-015-9502-y.
- Truong J, Yan AT, Cramarossa G, Chan KK. Chemotherapy-induced cardiotoxicity: detection, prevention, and management. Can J Cardiol. 2014 Aug;30(8):869-78. doi: 10.1016/j.cjca.2014.04.029. Epub 2014 May 4.
- Chicco AJ, Schneider CM, Hayward R. Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. J Cardiovasc Pharmacol. 2006 Feb;47(2):182-9. doi: 10.1097/01.fjc.0000199682.43448.2d.
- Hydock DS, Wonders KY, Schneider CM, Hayward R. Voluntary wheel running in rats receiving doxorubicin: effects on running activity and cardiac myosin heavy chain. Anticancer Res. 2009 Nov;29(11):4401-7.
- Hornsby WE, Douglas PS, West MJ, Kenjale AA, Lane AR, Schwitzer ER, Ray KA, Herndon JE 2nd, Coan A, Gutierrez A, Hornsby KP, Hamilton E, Wilke LG, Kimmick GG, Peppercorn JM, Jones LW. Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: a phase II randomized trial. Acta Oncol. 2014 Jan;53(1):65-74. doi: 10.3109/0284186X.2013.781673. Epub 2013 Aug 19.
- Gouspillou G, Scheede-Bergdahl C, Spendiff S, Vuda M, Meehan B, Mlynarski H, Archer-Lahlou E, Sgarioto N, Purves-Smith FM, Konokhova Y, Rak J, Chevalier S, Taivassalo T, Hepple RT, Jagoe RT. Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle. Sci Rep. 2015 Mar 3;5:8717. doi: 10.1038/srep08717.
- Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol. 2012 Jun;52(6):1213-25. doi: 10.1016/j.yjmcc.2012.03.006. Epub 2012 Mar 21.
- Perry CG, Lally J, Holloway GP, Heigenhauser GJ, Bonen A, Spriet LL. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010 Dec 1;588(Pt 23):4795-810. doi: 10.1113/jphysiol.2010.199448. Epub 2010 Oct 4.
- Stephens NA, Gallagher IJ, Rooyackers O, Skipworth RJ, Tan BH, Marstrand T, Ross JA, Guttridge DC, Lundell L, Fearon KC, Timmons JA. Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia. Genome Med. 2010 Jan 15;2(1):1. doi: 10.1186/gm122.
- Naressi A, Couturier C, Castang I, de Beer R, Graveron-Demilly D. Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals. Comput Biol Med. 2001 Jul;31(4):269-86. doi: 10.1016/s0010-4825(01)00006-3.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2020
Primary Completion (Estimated)
August 30, 2030
Study Completion (Estimated)
August 30, 2030
Study Registration Dates
First Submitted
July 2, 2020
First Submitted That Met QC Criteria
July 8, 2020
First Posted (Actual)
July 13, 2020
Study Record Updates
Last Update Posted (Estimated)
December 8, 2023
Last Update Submitted That Met QC Criteria
December 7, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2-049-18
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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