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Heart FailureNCT03084679

Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI in Heart Failure

A study testing Aerobic exercise in treadmill, Local strengthening exercises and Stretching exercises in people with Heart Failure, run by University of Campinas, Brazil at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The investigators hypothesised that novel MRI metrics derived from myocardium post-gadolinium T1 mapping analysis will improve the current knowledge about the role interstitial fibrosis and cardiomyocyte hypertrophy in the development of left ventricular (LV) remodelling and clinical Heart Failure (HF). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure
What is being tested?
Aerobic exercise in treadmill, Local strengthening exercises and Stretching exercises
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteBrazil
Study dates
1 Nov 2017to Jul 2020
Phase
Interventional
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age> 18 years
  • Functional limitation (New York Heart Association Class II or worse)
  • No contraindication to exercise (American College of Cardiology / American Heart Association criteria)
  • Eligibility to take MRI (absence of metallic devices, and glomerular filtration rate > 40ml / min / 1.73m2, etc.)
  • Prior diagnosis of Heart Failure (by the Framingham criterion)
  • Therapy with diuretic and euvolemia state (evaluated by cardiologist and cardiopulmonary exercise testing)
  • Transthoracic echocardiogram

Who cannot join

  • Severe ischemia in any stress test
  • Hypertrophic cardiomyopathy or any infiltrative heart disease
  • Chronic obstructive pulmonary disease , pulmonary hypertension (Pulmonary artery pressure> 60mmHg)
  • Severe left or right valve disease.
  • Pacemaker or implantable cardioverter defibrillator
  • Myocardial infarction or revascularization in 3 months
  • Anemia (hemoglobin <10 grams / dl) until 1 month before cardiopulmonary exercise testing

Trial locations and contacts

1 site in 1 country.

OTAVIO R COELHO-FILHO, MD, MPH, PhD contact

996038484 ext. +5519

tavicocoelho@gmail.com

FERNANDO B CARDOSO, MD contact

999203131 ext. +5519

fermedesportiva@yahoo.com.br

Brazil1 site, 1 recruiting

  • University of Campinas

    Campinas, São Paulo

    Otavio R Coelho Filho, MD, PhD, +5519996038484, tavicocoelho@gmail.com

    Fernando B Cardoso, MD, +5519999203131, fermedesportiva@yahoo.com.br

    Recruiting

Other trials in Brazil

About this study

Official title: Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure: Implication on Early Remodeling and on the Transition to Heart Failure

The investigators hypothesised that novel MRI metrics derived from myocardium post-gadolinium T1 mapping analysis will improve the current knowledge about the role interstitial fibrosis and cardiomyocyte hypertrophy in the development of left ventricular (LV) remodelling and clinical Heart Failure (HF). The investigators believe that these recently described variables will be associated with prognostically important indices in HF development.

Read the detailed description

Cardiac hypertrophy is one of the earliest manifestations of myocardial disease, representing a modifiable, prognostic response to hemodynamic stimuli across physiologic (e.g., exercise) and pathologic states (e.g., hypertension, aortic stenosis). The extent of myocardial hypertrophy is determined by a combination of cardiomyocyte size and extracellular volume (ECV) expansion/interstitial fibrosis: while physiologic (exercise-induced) hypertrophy reflects mostly reversible cardiomyocyte hypertrophy, pathologic hypertrophy (e.g., in heart failure) is a combination of both interstitial fibrosis (potentially irreversible) and cardiomyocyte hypertrophy (reversible). Current methods to delineate the potential for LV reverse remodeling (e.g., natriuretic peptides and echocardiographic or clinical markers) detect primarily advanced disease, missing a critical opportunity to intervene and follow patients at an early disease phase where myocardial pathology may be reversible. Therefore, establishing novel, quantitative metrics of myocardial tissue phenotype that define a transition from hypertrophy to fibrosis, and then to irreversible LV remodeling/dysfunction may facilitate targeting therapies at a modifiable stage of disease in HF. The investigator's group has recently extended cardiac T1 mapping MRI techniques to quantify the intracellular lifetime of water (τic) serially as an index of cardiomyocyte diameter, validating this technique histologically in mouse models of pressure overload.

Conditions
Heart Failure
Being tested
Aerobic exercise in treadmill, Local strengthening exercises, Stretching exercises
Keywords
Heart Failure, Hypertrophy, Fibrosis, Magnetic Resonance
Medical subject headings
Heart Failure, Hypertrophy, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aerobic exercise in treadmillOther

    30-40min of aerobic exercise in treadmill. The aerobic intensity will be established by heart rate levels that corresponded to anaerobic threshold up to 10% below the respiratory compensation point obtained in the cardiopulmonary exercise test. This intensity corresponded to 60-72% peak V̇o2. During the exercise sessions, when a training effect will be observed, as indicated by a decrease by 8 to 10% in heart rate, the treadmill velocity or inclination will be increased to return to the target heart rate levels.

  • Local strengthening exercisesOther

    15 min of local strengthening exercises will be performed in major muscle groups (legs, arms and trunk muscles): three series of each exercise, 12-15 repetitions.

  • Stretching exercisesOther

    5-min stretching exercises will be performed in major muscle groups (legs, arms and trunk muscles)

Study groups in NCT03084679
Study groupRoleWhat they receive
Conventional Clinical Care - HFpEFNo interventionHeart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.
Supervised Exercise Training- HFpEFOtherHeart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
Receives: Other: Aerobic exercise in treadmill; Other: Local strengthening exercises; Other: Stretching exercises
Conventional Clinical Care - HFrEFNo interventionHeart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.
Supervised Exercise Training - HFrEFOtherHeart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
Receives: Other: Aerobic exercise in treadmill; Other: Local strengthening exercises; Other: Stretching exercises

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Myocardial remodeling assessed by CMR in rehabilitation vs usual care.

    Investigate whether rehabilitation compared to usual care is associated with significant favorable myocardial remodeling assessed by CMR determination of ECV.

    Measured: 4 months

Secondary outcomes (17)

  1. Change in left ventricular ejection fraction

    Left Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  2. Change in right ventricular ejection fraction

    Right Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  3. Change in left ventricular mass (absolute/index)

    Left ventricular mass absolute (g) and index (g/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  4. Change in left ventricular diastolic volume (absolute/index)

    Left ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  5. Change in right ventricular diastolic volume (absolute/index)

    Right ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  6. Change in left ventricular systolic volume (absolute/index)

    Left ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  7. Change in right ventricular systolic volume (absolute/index)

    Right ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  8. Change in left ventricular stroke volume (absolute/index)

    Left ventricular stroke volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  9. Change in right ventricular stroke volume (absolute/index)

    Right ventricular stroke volume (absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  10. Change in late gadolinium enhancement

    Late gadolinium enhancement (LGE) will be determined by cardiac magnetic resonance using a previously describe inversion recovery sequence after 10-15 minutes of a cumulative dose of 0,2 mmol/kg of gadolinium diethylenetriamine pentaacetic acid. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  11. Change in LV mass/volume ratio

    LV mass/volume ratio (g/mL) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.

    Measured: 4 months

  12. Change in functional capacity

    VO2max will be evaluated by cardiopulmonary test. Patients will performed the cardiopulmonary test at baseline and after 4 months of the intervention.

    Measured: 4 months

  13. Change in quality of life

    Quality of life will be evaluated by numerical score of Minnesota Questionnaire.

    Patients will performed the Minnesota Questionnaire at baseline and after 4 months of the intervention.

    Measured: 4 months

  14. Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP)

    Change in NT-proBNP with the intervention.

    Measured: 4 months

  15. Change in diastolic dysfunction assessed by transthoracic echocardiogram

    Change in parameters of diastolic dysfunction assessed before and after the intervention.

    Measured: 4 months

  16. Change in cardiac sympathetic function

    Change in cardiac sympathetic function assessed by cardiac uptake of metaiodobenzylguanidine (MIBG) labeled with I-123. Patients will performed the MIBG study at baseline and after 4 months of the intervention.

    Measured: 4 months

  17. Change in intracellular lifetime of water (τic - a marker of cardiomyocyte hypertrophy)

    τic will be determined by cardiac magnetic resonance T1 measurements acquired before and after administration of gadolinium diethylenetriamine pentaacetic acid (0,2mmol/kg), at 2 different time points (baseline and 4-moths after the intervention)

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2017
  2. Study start1 Nov 2017
  3. Primary completion1 Jun 2019 (estimated)
  4. Study completionJul 2020 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized trial in a 2:1 (intervention:control) proportion and in blocks of 6 participants.
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03084679
Sponsor's protocol ID
HF-CMR-53967215800005404
Other IDs
FAPESP 2015/15402-2
Status last verified
Jun 2019
First submitted
25 Dec 2016
Last updated
5 Jun 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No plan to Share individual participant data.

Publications

  • Dorn GW 2nd, Robbins J, Sugden PH. Phenotyping hypertrophy: eschew obfuscation. Circ Res. 2003 Jun 13;92(11):1171-5. doi: 10.1161/01.RES.0000077012.11088.BC. No abstract available.

    PubMed 12805233

  • Boluyt MO, O'Neill L, Meredith AL, Bing OH, Brooks WW, Conrad CH, Crow MT, Lakatta EG. Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res. 1994 Jul;75(1):23-32. doi: 10.1161/01.res.75.1.23.

    PubMed 8013079

  • Lorell BH, Carabello BA; New Collective Author. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000 Jul 25;102(4):470-9. doi: 10.1161/01.cir.102.4.470. No abstract available.

    PubMed 10908222

  • Scimia MC, Hurtado C, Ray S, Metzler S, Wei K, Wang J, Woods CE, Purcell NH, Catalucci D, Akasaka T, Bueno OF, Vlasuk GP, Kaliman P, Bodmer R, Smith LH, Ashley E, Mercola M, Brown JH, Ruiz-Lozano P. APJ acts as a dual receptor in cardiac hypertrophy. Nature. 2012 Aug 16;488(7411):394-8. doi: 10.1038/nature11263.

    PubMed 22810587

  • Gunja-Smith Z, Morales AR, Romanelli R, Woessner JF Jr. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol. 1996 May;148(5):1639-48.

    PubMed 8623931

  • Hughes SE. Detection of apoptosis using in situ markers for DNA strand breaks in the failing human heart. Fact or epiphenomenon? J Pathol. 2003 Oct;201(2):181-6. doi: 10.1002/path.1447.

    PubMed 14517834

  • Kostin S, Hein S, Arnon E, Scholz D, Schaper J. The cytoskeleton and related proteins in the human failing heart. Heart Fail Rev. 2000 Oct;5(3):271-80. doi: 10.1023/A:1009813621103.

    PubMed 16228910

  • Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996 Oct 17;335(16):1182-9. doi: 10.1056/NEJM199610173351603.

    PubMed 8815940

  • Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P. Apoptosis in the failing human heart. N Engl J Med. 1997 Apr 17;336(16):1131-41. doi: 10.1056/NEJM199704173361603.

    PubMed 9099657

  • Unverferth DV, Fetters JK, Unverferth BJ, Leier CV, Magorien RD, Arn AR, Baker PB. Human myocardial histologic characteristics in congestive heart failure. Circulation. 1983 Dec;68(6):1194-200. doi: 10.1161/01.cir.68.6.1194.

    PubMed 6640872

  • Zorc M, Vraspir-Porenta O, Zorc-Pleskovic R, Radovanovic N, Petrovic D. Apoptosis of myocytes and proliferation markers as prognostic factors in end-stage dilated cardiomyopathy. Cardiovasc Pathol. 2003 Jan-Feb;12(1):36-9. doi: 10.1016/s1054-8807(02)00134-5.

    PubMed 12598016

  • Yamada Y, Saito S, Nishinaka T, Yamazaki K. Myocardial size and fibrosis changes during left ventricular assist device support. ASAIO J. 2012 Jul-Aug;58(4):402-6. doi: 10.1097/MAT.0b013e31825b9826.

    PubMed 22739784

  • Bruckner BA, Razeghi P, Stetson S, Thompson L, Lafuente J, Entman M, Loebe M, Noon G, Taegtmeyer H, Frazier OH, Youker K. Degree of cardiac fibrosis and hypertrophy at time of implantation predicts myocardial improvement during left ventricular assist device support. J Heart Lung Transplant. 2004 Jan;23(1):36-42. doi: 10.1016/s1053-2498(03)00103-7.

    PubMed 14734125

  • Aoki T, Fukumoto Y, Sugimura K, Oikawa M, Satoh K, Nakano M, Nakayama M, Shimokawa H. Prognostic impact of myocardial interstitial fibrosis in non-ischemic heart failure. -Comparison between preserved and reduced ejection fraction heart failure.-. Circ J. 2011;75(11):2605-13. doi: 10.1253/circj.cj-11-0568. Epub 2011 Aug 6.

    PubMed 21821961

  • Aronow BJ, Toyokawa T, Canning A, Haghighi K, Delling U, Kranias E, Molkentin JD, Dorn GW 2nd. Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy. Physiol Genomics. 2001 Jun 6;6(1):19-28. doi: 10.1152/physiolgenomics.2001.6.1.19.

    PubMed 11395543

Questions about this trial

What is this clinical trial studying?

A study testing Aerobic exercise in treadmill, Local strengthening exercises and Stretching exercises in people with Heart Failure, run by University of Campinas, Brazil at 1 site in Brazil.

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 7 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 5 Jun 2019. 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 Brazil. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact OTAVIO R COELHO-FILHO, MD, MPH, PhD (996038484 ext. +5519, tavicocoelho@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Myocardial remodeling assessed by CMR in rehabilitation vs usual care. (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03084679, which also lists 44 linked publications.

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 5 Jun 2019.

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