Pilot Study of Cardiac MR in Patients With Muscular Dystrophy

Musculoskeletal Diseases Clinical Trial

Official title:

Pilot Study of Cardiac Magnetic Resonance in Patients With Muscular Dystrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02921321
• Other study ID #: 4193
• Secondary ID: Internal Bridge
• Status: Active, not recruiting
• Start date: January 2014
• Est. completion date: December 2024

Study information

• Verified date: September 2023
• Source: Children's National Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Muscular Dystrophy can affect the skeletal muscles and also the heart and breathing muscles, causing significant morbidity and mortality. As patients are now living longer, treatment of muscular dystrophies involves drugs that help improve heart function. However, better types of heart imaging studies are needed to understand how these treatments work. Researchers want to improve heart imaging to identify earlier indicators of heart dysfunction in muscular dystrophy patients and how these are changed by medical treatment. The new imaging indicators will also help identify candidates for entry into future clinical trials.

Description:

Cardiomyopathy causes significant morbidity and mortality in multiple forms of muscular dystrophy affecting children, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2). Pharmaceutical treatments for the cardiomyopathy of muscular dystrophy, including angiotensin-converting enzyme (ACE) inhibition and beta-adrenergic receptor blockade, afford significant benefit and demonstrate cardiac remodeling in clinical studies. Further studies are needed to identify and characterize more sensitive indicators of cardiac dysfunction in muscular dystrophy subjects to better stratify subjects for entry into clinical protocols.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Duchenne, Becker, or Limb Girdle Muscular Dystrophy

Exclusion Criteria:

• Day-time users of continuous positive airway pressure (CPAP)
• Sip ventilator users
• Invasive ventilator dependent
• Pregnant minors or adults (when uncertain, participants will undergo urine testing) or lactating minors and adults
• Females who are nursing and who do not plan to discard breast milk for 24 hours
• Decompensated congestive heart failure (unable to lie flat during CMR)
• Impaired renal excretory function (calculated Glomerular Filtration Rate less than 30 milliliters/min)
• Contra-indications to Magnetic Resonance Imaging:
• Cardiac pacemaker or implantable defibrillator
• Cerebral aneurysm clip
• Neural stimulator
• Metallic ocular foreign body
• Any implanted device (i.e. insulin pump, drug infusion device)
• Claustrophobia
• Metal shrapnel or bullet
• Investigator assessment of inability to comply with protocol
• Unable/unwilling to lie still throughout the research procedure or who require sedation
• Persons with cognitive impairment

Related Conditions & MeSH terms

• Cardiac Fibrosis
• Genetic Diseases, Inborn
• Muscular Dystrophies
• Musculoskeletal Diseases

Locations

Country	Name	City	State
United States	Children's National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's National Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (51)

Anderson KP, Walker R, Urie P, Ershler PR, Lux RL, Karwandee SV. Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy. J Clin Invest. 1993 Jul;92(1):122-40. doi: 10.1172/JCI116540. — View Citation

Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Sonnenblick EH, Olivetti G, Anversa P. The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol. 1995 Jan;27(1):291-305. doi: 10.1016/s0022-2828(08)80028-4. — View Citation

Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, Folsom AR. The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008 Dec 16;52(25):2148-55. doi: 10.1016/j.jacc.2008.09.014. — View Citation

Bottini PB, Carr AA, Prisant LM, Flickinger FW, Allison JD, Gottdiener JS. Magnetic resonance imaging compared to echocardiography to assess left ventricular mass in the hypertensive patient. Am J Hypertens. 1995 Mar;8(3):221-8. doi: 10.1016/0895-7061(94)00178-E. — View Citation

Caiani EG, Corsi C, Sugeng L, MacEneaney P, Weinert L, Mor-Avi V, Lang RM. Improved quantification of left ventricular mass based on endocardial and epicardial surface detection with real time three dimensional echocardiography. Heart. 2006 Feb;92(2):213-9. doi: 10.1136/hrt.2005.060889. Epub 2005 May 12. — View Citation

Cao Y, Huang DQ, Shih G, Prince MR. Signal Change in the Dentate Nucleus on T1-Weighted MR Images After Multiple Administrations of Gadopentetate Dimeglumine Versus Gadobutrol. AJR Am J Roentgenol. 2016 Feb;206(2):414-9. doi: 10.2214/AJR.15.15327. Epub 2015 Dec 23. — View Citation

Castillo E, Osman NF, Rosen BD, El-Shehaby I, Pan L, Jerosch-Herold M, Lai S, Bluemke DA, Lima JA. Quantitative assessment of regional myocardial function with MR-tagging in a multi-center study: interobserver and intraobserver agreement of fast strain analysis with Harmonic Phase (HARP) MRI. J Cardiovasc Magn Reson. 2005;7(5):783-91. doi: 10.1080/10976640500295417. — View Citation

Corrado G, Lissoni A, Beretta S, Terenghi L, Tadeo G, Foglia-Manzillo G, Tagliagambe LM, Spata M, Santarone M. Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol. 2002 Apr 1;89(7):838-41. doi: 10.1016/s0002-9149(02)02195-1. — View Citation

Cox GF, Kunkel LM. Dystrophies and heart disease. Curr Opin Cardiol. 1997 May;12(3):329-43. — View Citation

de Bakker JM, van Capelle FJ, Janse MJ, Tasseron S, Vermeulen JT, de Jonge N, Lahpor JR. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol. 1996 Apr;27(5):1071-8. doi: 10.1016/0735-1097(95)00612-5. — View Citation

de Lemos JA, McGuire DK, Khera A, Das SR, Murphy SA, Omland T, Drazner MH. Screening the population for left ventricular hypertrophy and left ventricular systolic dysfunction using natriuretic peptides: results from the Dallas Heart Study. Am Heart J. 2009 Apr;157(4):746-53.e2. doi: 10.1016/j.ahj.2008.12.017. Epub 2009 Feb 20. — View Citation

de Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation. 1996 Jan 15;93(2):259-65. doi: 10.1161/01.cir.93.2.259. — View Citation

Deburgrave N, Daoud F, Llense S, Barbot JC, Recan D, Peccate C, Burghes AH, Beroud C, Garcia L, Kaplan JC, Chelly J, Leturcq F. Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. Hum Mutat. 2007 Feb;28(2):183-95. doi: 10.1002/humu.20422. — View Citation

Devereux RB, Dahlof B, Gerdts E, Boman K, Nieminen MS, Papademetriou V, Rokkedal J, Harris KE, Edelman JM, Wachtell K. Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation. 2004 Sep 14;110(11):1456-62. doi: 10.1161/01.CIR.0000141573.44737.5A. Epub 2004 Aug 23. — View Citation

Devereux RB, Lutas EM, Casale PN, Kligfield P, Eisenberg RR, Hammond IW, Miller DH, Reis G, Alderman MH, Laragh JH. Standardization of M-mode echocardiographic left ventricular anatomic measurements. J Am Coll Cardiol. 1984 Dec;4(6):1222-30. doi: 10.1016/s0735-1097(84)80141-2. — View Citation

Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, Rokkedal J, Harris K, Aurup P, Dahlof B. Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA. 2004 Nov 17;292(19):2350-6. doi: 10.1001/jama.292.19.2350. — View Citation

Fernandes VR, Polak JF, Cheng S, Rosen BD, Carvalho B, Nasir K, McClelland R, Hundley G, Pearson G, O'Leary DH, Bluemke DA, Lima JA. Arterial stiffness is associated with regional ventricular systolic and diastolic dysfunction: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):194-201. doi: 10.1161/ATVBAHA.107.156950. Epub 2007 Oct 25. — View Citation

Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology. 2001 Mar;218(3):703-10. doi: 10.1148/radiology.218.3.r01fe18703. — View Citation

Gardin JM, McClelland R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS, Wong ND, Smith VE, Gottdiener J. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001 May 1;87(9):1051-7. doi: 10.1016/s0002-9149(01)01460-6. — View Citation

Haider AW, Larson MG, Benjamin EJ, Levy D. Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death. J Am Coll Cardiol. 1998 Nov;32(5):1454-9. doi: 10.1016/s0735-1097(98)00407-0. — View Citation

Harris PA, Lorenz CH, Holburn GE, Overholser KA. Regional measurement of the Gd-DTPA tissue partition coefficient in canine myocardium. Magn Reson Med. 1997 Oct;38(4):541-5. doi: 10.1002/mrm.1910380406. — View Citation

Hees PS, Fleg JL, Lakatta EG, Shapiro EP. Left ventricular remodeling with age in normal men versus women: novel insights using three-dimensional magnetic resonance imaging. Am J Cardiol. 2002 Dec 1;90(11):1231-6. doi: 10.1016/s0002-9149(02)02840-0. — View Citation

Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919-28. doi: 10.1016/0092-8674(87)90579-4. — View Citation

Hollingsworth KG, Garrood P, Eagle M, Bushby K, Straub V. Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months. Muscle Nerve. 2013 Oct;48(4):586-8. doi: 10.1002/mus.23879. Epub 2013 Aug 30. — View Citation

Jerosch-Herold M, Sheridan DC, Kushner JD, Nauman D, Burgess D, Dutton D, Alharethi R, Li D, Hershberger RE. Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1234-H1242. doi: 10.1152/ajpheart.00429.2008. Epub 2008 Jul 25. — View Citation

Jost G, Lenhard DC, Sieber MA, Lohrke J, Frenzel T, Pietsch H. Signal Increase on Unenhanced T1-Weighted Images in the Rat Brain After Repeated, Extended Doses of Gadolinium-Based Contrast Agents: Comparison of Linear and Macrocyclic Agents. Invest Radiol. 2016 Feb;51(2):83-9. doi: 10.1097/RLI.0000000000000242. — View Citation

Kannel WB, Gordon T, Castelli WP, Margolis JR. Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease. The Framingham study. Ann Intern Med. 1970 Jun;72(6):813-22. doi: 10.7326/0003-4819-72-6-813. No abstract available. — View Citation

Kawara T, Derksen R, de Groot JR, Coronel R, Tasseron S, Linnenbank AC, Hauer RN, Kirkels H, Janse MJ, de Bakker JM. Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation. 2001 Dec 18;104(25):3069-75. doi: 10.1161/hc5001.100833. — View Citation

Kjeldsen SE, Dahlof B, Devereux RB, Julius S, Aurup P, Edelman J, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristianson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Snapinn S, Wedel H; LIFE (Losartan Intervention for Endpoint Reduction) Study Group. Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA. 2002 Sep 25;288(12):1491-8. doi: 10.1001/jama.288.12.1491. — View Citation

Lavie CJ, Milani RV, Ventura HO, Messerli FH. Left ventricular geometry and mortality in patients >70 years of age with normal ejection fraction. Am J Cardiol. 2006 Nov 15;98(10):1396-9. doi: 10.1016/j.amjcard.2006.06.037. Epub 2006 Oct 2. — View Citation

Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Left ventricular mass and incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study. Ann Intern Med. 1989 Jan 15;110(2):101-7. doi: 10.7326/0003-4819-110-2-101. — View Citation

Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31;322(22):1561-6. doi: 10.1056/NEJM199005313222203. — View Citation

Lim LE, Campbell KP. The sarcoglycan complex in limb-girdle muscular dystrophy. Curr Opin Neurol. 1998 Oct;11(5):443-52. doi: 10.1097/00019052-199810000-00006. — View Citation

Mathews KD, Moore SA. Limb-girdle muscular dystrophy. Curr Neurol Neurosci Rep. 2003 Jan;3(1):78-85. doi: 10.1007/s11910-003-0042-9. — View Citation

McLenachan JM, Dargie HJ. Ventricular arrhythmias in hypertensive left ventricular hypertrophy. Relationship to coronary artery disease, left ventricular dysfunction, and myocardial fibrosis. Am J Hypertens. 1990 Oct;3(10):735-40. doi: 10.1093/ajh/3.10.735. — View Citation

Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, King W, Signore L, Pandya S, Florence J, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. doi: 10.1056/NEJM198906153202405. — View Citation

Nadarajah VD, van Putten M, Chaouch A, Garrood P, Straub V, Lochmuller H, Ginjaar HB, Aartsma-Rus AM, van Ommen GJ, den Dunnen JT, 't Hoen PA. Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in Duchenne muscular dystrophy (DMD). Neuromuscul Disord. 2011 Aug;21(8):569-78. doi: 10.1016/j.nmd.2011.05.011. Epub 2011 Jul 2. — View Citation

Niendorf HP, Haustein J, Cornelius I, Alhassan A, Clauss W. Safety of gadolinium-DTPA: extended clinical experience. Magn Reson Med. 1991 Dec;22(2):222-8; discussion 229-32. doi: 10.1002/mrm.1910220212. — View Citation

Nigro G, Comi LI, Politano L, Bain RJ. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol. 1990 Mar;26(3):271-7. doi: 10.1016/0167-5273(90)90082-g. — View Citation

Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Wedel H, Lindholm LH, Dahlof B; LIFE Study Investigators. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA. 2004 Nov 17;292(19):2343-9. doi: 10.1001/jama.292.19.2343. — View Citation

Osman NF, Prince JL. Visualizing myocardial function using HARP MRI. Phys Med Biol. 2000 Jun;45(6):1665-82. doi: 10.1088/0031-9155/45/6/318. — View Citation

Pack NA, Dibella EV, Wilson BD, McGann CJ. Quantitative myocardial distribution volume from dynamic contrast-enhanced MRI. Magn Reson Imaging. 2008 May;26(4):532-42. doi: 10.1016/j.mri.2007.10.003. Epub 2008 Feb 20. — View Citation

Rosen BD, Saad MF, Shea S, Nasir K, Edvardsen T, Burke G, Jerosch-Herold M, Arnett DK, Lai S, Bluemke DA, Lima JA. Hypertension and smoking are associated with reduced regional left ventricular function in asymptomatic: individuals the Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol. 2006 Mar 21;47(6):1150-8. doi: 10.1016/j.jacc.2005.08.078. Epub 2006 Feb 23. — View Citation

Rossi MA. Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J Hypertens. 1998 Jul;16(7):1031-41. doi: 10.1097/00004872-199816070-00018. — View Citation

Solomon SD, Appelbaum E, Manning WJ, Verma A, Berglund T, Lukashevich V, Cherif Papst C, Smith BA, Dahlof B; Aliskiren in Left Ventricular Hypertrophy (ALLAY) Trial Investigators. Effect of the direct Renin inhibitor aliskiren, the Angiotensin receptor blocker losartan, or both on left ventricular mass in patients with hypertension and left ventricular hypertrophy. Circulation. 2009 Feb 3;119(4):530-7. doi: 10.1161/CIRCULATIONAHA.108.826214. Epub 2009 Jan 19. — View Citation

Turakhia MP, Schiller NB, Whooley MA. Prognostic significance of increased left ventricular mass index to mortality and sudden death in patients with stable coronary heart disease (from the Heart and Soul Study). Am J Cardiol. 2008 Nov 1;102(9):1131-5. doi: 10.1016/j.amjcard.2008.06.036. Epub 2008 Aug 27. — View Citation

van Hoeven KH, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease. Circulation. 1990 Sep;82(3):848-55. doi: 10.1161/01.cir.82.3.848. — View Citation

Verdecchia P, Carini G, Circo A, Dovellini E, Giovannini E, Lombardo M, Solinas P, Gorini M, Maggioni AP; MAVI (MAssa Ventricolare sinistra nell'Ipertensione) Study Group. Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study. J Am Coll Cardiol. 2001 Dec;38(7):1829-35. doi: 10.1016/s0735-1097(01)01663-1. — View Citation

Viollet L, Gailey S, Thornton DJ, Friedman NR, Flanigan KM, Mahan JD, Mendell JR. Utility of cystatin C to monitor renal function in Duchenne muscular dystrophy. Muscle Nerve. 2009 Sep;40(3):438-42. doi: 10.1002/mus.21420. — View Citation

Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991 Jun;83(6):1849-65. doi: 10.1161/01.cir.83.6.1849. — View Citation

Wu YL, Ye Q, Sato K, Foley LM, Hitchens TK, Ho C. Noninvasive evaluation of cardiac allograft rejection by cellular and functional cardiac magnetic resonance. JACC Cardiovasc Imaging. 2009 Jun;2(6):731-41. doi: 10.1016/j.jcmg.2009.01.013. — View Citation

* Note: There are 51 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial characterization of fibrosis in patients with muscular dystrophy using contrast based magnetic resonance imaging		At the end of each MRI scan through study completion, up to 5 years.
Secondary	Measure the amount of intramyocardial fibrosis using extracellular volume measurements		At the end of each MRI scan through study completion, up to 5 years.
Secondary	Identification and validation of serum biomarker ST2 (Interleukin 1 receptor-like 1 protein ) in the presence of myocardial fibrosis.		At the end of the study, up to 10 years
Secondary	Measure regional myocardial strain and correlate with presence of myocardial fibrosis		At the end of each MRI scan through study completion, up to 5 years.