Association of Insulin Resistance and FGF21 on Cardiac Function in Pediatric Dilated Cardiomyopathy

Insulin Resistance Clinical Trial

Official title:

Association of Insulin Resistance and FGF21 on Cardiac Function in Pediatric Dilated Cardiomyopathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04222101
• Other study ID #: 19-06748-FB
• Status: Terminated
• Phase: N/A
• Start date: October 7, 2019
• Est. completion date: June 30, 2021

Study information

• Verified date: December 2021
• Source: Le Bonheur Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate whether there is an association between insulin resistance and cardiac function in children with dilated or hypertrophic cardiomyopathy. This study will also investigate whether there is an association between FGF21 and cardiac function in children with dilated or hypertrophic cardiomyopathy and whether this is mediated through greater insulin resistance and/or through independent effects.

Description:

Although pediatric cardiomyopathy is rare, the condition is severe and life-threatening. The main focus of this proposed study will examine whether insulin resistance is correlated with decreased cardiac function which will hopefully pave the way for future clinical trials using medications that sensitize insulin such as metformin or glucagon-like peptide-1 (GLP-1 agonists) as possible therapeutic agents. The exploratory piece of this study will investigate a novel therapeutic target by determining whether FGF21 has any direct effects on cardiac function and whether it interacts with insulin resistance in altering cardiac function. Patients with cardiomyopathy normally undergo ECHO as part of routine evaluation and follow up and is standard of care. At this time, there are no official guidelines for pediatric patients with cardiomyopathy to undergo oral glucose tolerance testing (OGTT) and thus it is not part of the standard of care. Based on findings from this study, the investigators hope to justify performing an OGTT on pediatric patients with dilated or hypertrophic cardiomyopathy and incorporate the procedure in future practice guidelines.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 13 Years to 18 Years

Eligibility

Inclusion Criteria:

• Diagnosis of dilated or hypertrophic cardiomyopathy

• Pubertal (Tanner 2 breast in females or testicular volume = 4mL in males)

• Permission by the primary cardiologist of the patient for enrollment in the study

Exclusion Criteria:

• Prior diagnosis of diabetes and treatment with anti-diabetes medication

• Neuromuscular disorder

• Inborn error of metabolism

• Malformation syndrome

• Clinically unstable based on the assessment of the primary cardiologist caring for the patient

• inability of parent/legal guardian to provide informed consent

• non-English speaking

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Cardiomyopathy, Hypertrophic
• Insulin Resistance

Intervention

Diagnostic Test:
• Oral glucose tolerance test
measure insulin, glucose and FGF21 levels in response to oral glucose challenge

Locations

Country	Name	City	State
United States	Le Bonheur Children's Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Le Bonheur Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (11)

Camporez JP, Jornayvaz FR, Petersen MC, Pesta D, Guigni BA, Serr J, Zhang D, Kahn M, Samuel VT, Jurczak MJ, Shulman GI. Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice. Endocrinology. 2013 Sep;154(9):3099-109. doi: 10.1210/en.2013-1191. Epub 2013 Jun 13. — View Citation

Dávila-Román VG, Vedala G, Herrero P, de las Fuentes L, Rogers JG, Kelly DP, Gropler RJ. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2002 Jul 17;40(2):271-7. — View Citation

Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78:223-41. doi: 10.1146/annurev-physiol-021115-105339. Epub 2015 Nov 19. Review. — View Citation

Neglia D, De Caterina A, Marraccini P, Natali A, Ciardetti M, Vecoli C, Gastaldelli A, Ciociaro D, Pellegrini P, Testa R, Menichetti L, L'Abbate A, Stanley WC, Recchia FA. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3270-8. Epub 2007 Oct 5. — View Citation

Nikolaidis LA, Sturzu A, Stolarski C, Elahi D, Shen YT, Shannon RP. The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy. Cardiovasc Res. 2004 Feb 1;61(2):297-306. — View Citation

Riehle C, Abel ED. Insulin Signaling and Heart Failure. Circ Res. 2016 Apr 1;118(7):1151-69. doi: 10.1161/CIRCRESAHA.116.306206. Review. — View Citation

Sakai Y, Maruyama T, Katsuta H, Kogawa K, Akashi T, Izumi K, Tominaga H, Kono S, Nagafuchi S, Harada M. Patients with dilated cardiomyopathy possess insulin resistance independently of cardiac dysfunction or serum tumor necrosis factor-alpha. Int Heart J. — View Citation

Shah A, Shannon RP. Insulin resistance in dilated cardiomyopathy. Rev Cardiovasc Med. 2003;4 Suppl 6:S50-7. Review. — View Citation

Swan JW, Anker SD, Walton C, Godsland IF, Clark AL, Leyva F, Stevenson JC, Coats AJ. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol. 1997 Aug;30(2):527-32. — View Citation

Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006 Oct 18;296(15):1867-76. — View Citation

Witteles RM, Tang WH, Jamali AH, Chu JW, Reaven GM, Fowler MB. Insulin resistance in idiopathic dilated cardiomyopathy: a possible etiologic link. J Am Coll Cardiol. 2004 Jul 7;44(1):78-81. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whole body insulin sensitivity index	correlate whole body insulin sensitivity index with left ventricular ejection fraction	baseline
Secondary	FGF21 level	correlate FGF21 levels with whole body sensitivity index and left ventricular ejection fraction	baseline