Efficacy of LoDoCo in Improving Exercise Capacity Among Patients With HFpEF and Inflammation

Summary

The purpose of this research study is to determine the effectiveness of low dose colchicine (LoDoCo) on measures of exercise capacity, physical function, frailty, and quality of life, among patients with heart failure with chronic stable preserved ejection fraction (HFpEF) and systemic inflammation. The use of LoDoCo in this study is considered investigational as it has not been approved by the Food and Drug Administration (FDA) for the treatment of exercise capacity in patients with HFpEF. Participants will undergo a 1-day screening that includes a blood draw and physical examination. If deemed eligible for the study, participants will undergo a baseline visit within 2 weeks of screening visit that includes physical examination, exercise testing, echocardiography and completion of quality-of-life surveys. Participants will also be randomized at this visit (randomly assigned to a group) to receive either LoDoCo or placebo (inactive substance) for 3 months. Participants will be called back at 3 months for repeat physical examination, blood draws, echocardiography, exercise testing and completion of quality-of-life surveys. Each visit will take about 3 hours. Total study duration is about 3 months.

Timeline

Start

2024-04-24

Primary completion

2026-07-31

Completion

2027-12-31

Publications

• Background Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
• Background Nayor M, Houstis NE, Namasivayam M, Rouvina J, Hardin C, Shah RV, Ho JE, Malhotra R, Lewis GD. Impaired Exercise Tolerance in Heart Failure With Preserved Ejection Fraction: Quantification of Multiorgan System Reserve Capacity. JACC Heart Fail. 2020 Aug;8(8):605-617. doi: 10.1016/j.jchf.2020.03.008. Epub 2020 Jun 10.
• Background Pandey A, Shah SJ, Butler J, Kellogg DL Jr, Lewis GD, Forman DE, Mentz RJ, Borlaug BA, Simon MA, Chirinos JA, Fielding RA, Volpi E, Molina AJA, Haykowsky MJ, Sam F, Goodpaster BH, Bertoni AG, Justice JN, White JP, Ding J, Hummel SL, LeBrasseur NK, Taffet GE, Pipinos II, Kitzman D. Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 14;78(11):1166-1187. doi: 10.1016/j.jacc.2021.07.014.
• Background Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, Harrison DG, Liu Y, Hoffmann U, Bauer DC, Newman AB, Kritchevsky SB, Harris TB, Butler J; Health ABC Study Investigators. Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol. 2010 May 11;55(19):2129-37. doi: 10.1016/j.jacc.2009.12.045.
• Background Schiattarella GG, Altamirano F, Tong D, French KM, Villalobos E, Kim SY, Luo X, Jiang N, May HI, Wang ZV, Hill TM, Mammen PPA, Huang J, Lee DI, Hahn VS, Sharma K, Kass DA, Lavandero S, Gillette TG, Hill JA. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019 Apr;568(7752):351-356. doi: 10.1038/s41586-019-1100-z. Epub 2019 Apr 10.
• Background Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tschope C, Leite-Moreira AF, Musters R, Niessen HW, Linke WA, Paulus WJ, Hamdani N. Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2016 Apr;4(4):312-24. doi: 10.1016/j.jchf.2015.10.007. Epub 2015 Dec 9.
• Background Westermann D, Lindner D, Kasner M, Zietsch C, Savvatis K, Escher F, von Schlippenbach J, Skurk C, Steendijk P, Riad A, Poller W, Schultheiss HP, Tschope C. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011 Jan;4(1):44-52. doi: 10.1161/CIRCHEARTFAILURE.109.931451. Epub 2010 Nov 12.
• Background DuBrock HM, AbouEzzeddine OF, Redfield MM. High-sensitivity C-reactive protein in heart failure with preserved ejection fraction. PLoS One. 2018 Aug 16;13(8):e0201836. doi: 10.1371/journal.pone.0201836. eCollection 2018.
• Background Tromp J, Khan MA, Klip IT, Meyer S, de Boer RA, Jaarsma T, Hillege H, van Veldhuisen DJ, van der Meer P, Voors AA. Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction. J Am Heart Assoc. 2017 Mar 30;6(4):e003989. doi: 10.1161/JAHA.116.003989.
• Background Hage C, Michaelsson E, Linde C, Donal E, Daubert JC, Gan LM, Lund LH. Inflammatory Biomarkers Predict Heart Failure Severity and Prognosis in Patients With Heart Failure With Preserved Ejection Fraction: A Holistic Proteomic Approach. Circ Cardiovasc Genet. 2017 Feb;10(1):e001633. doi: 10.1161/CIRCGENETICS.116.001633.
• Background Kitzman DW, Haykowsky MJ, Tomczak CR. Making the Case for Skeletal Muscle Myopathy and Its Contribution to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2017 Jul;10(7):e004281. doi: 10.1161/CIRCHEARTFAILURE.117.004281. No abstract available.
• Background Fleg JL, Cooper LS, Borlaug BA, Haykowsky MJ, Kraus WE, Levine BD, Pfeffer MA, Pina IL, Poole DC, Reeves GR, Whellan DJ, Kitzman DW; National Heart, Lung, and Blood Institute Working Group. Exercise training as therapy for heart failure: current status and future directions. Circ Heart Fail. 2015 Jan;8(1):209-20. doi: 10.1161/CIRCHEARTFAILURE.113.001420. No abstract available.
• Background Warraich HJ, Kitzman DW, Whellan DJ, Duncan PW, Mentz RJ, Pastva AM, Nelson MB, Upadhya B, Reeves GR. Physical Function, Frailty, Cognition, Depression, and Quality of Life in Hospitalized Adults >/=60 Years With Acute Decompensated Heart Failure With Preserved Versus Reduced Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005254. doi: 10.1161/CIRCHEARTFAILURE.118.005254.
• Background Chiarantini D, Volpato S, Sioulis F, Bartalucci F, Del Bianco L, Mangani I, Pepe G, Tarantini F, Berni A, Marchionni N, Di Bari M. Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure. J Card Fail. 2010 May;16(5):390-5. doi: 10.1016/j.cardfail.2010.01.004. Epub 2010 Mar 3.
• Background Pandey A, Kitzman D, Whellan DJ, Duncan PW, Mentz RJ, Pastva AM, Nelson MB, Upadhya B, Chen H, Reeves GR. Frailty Among Older Decompensated Heart Failure Patients: Prevalence, Association With Patient-Centered Outcomes, and Efficient Detection Methods. JACC Heart Fail. 2019 Dec;7(12):1079-1088. doi: 10.1016/j.jchf.2019.10.003.
• Background Murad K, Goff DC Jr, Morgan TM, Burke GL, Bartz TM, Kizer JR, Chaudhry SI, Gottdiener JS, Kitzman DW. Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study. JACC Heart Fail. 2015 Jul;3(7):542-550. doi: 10.1016/j.jchf.2015.03.004.
• Background Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, Wehrens XH, Deswal A. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012 Mar 13;59(11):998-1005. doi: 10.1016/j.jacc.2011.11.040.
• Background Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, Eggebeen J, Nicklas BJ. Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2016 Jan 5;315(1):36-46. doi: 10.1001/jama.2015.17346.
• Background Van Tassell BW, Buckley LF, Carbone S, Trankle CR, Canada JM, Dixon DL, Abouzaki N, Oddi-Erdle C, Biondi-Zoccai G, Arena R, Abbate A. Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2). Clin Cardiol. 2017 Sep;40(9):626-632. doi: 10.1002/clc.22719. Epub 2017 May 5.
• Background Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.

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