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

NCT06130059 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STU-2023-0964
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure; Inflammation

Outcome Measures

Primary Outcomes (1)

• Peak VO2 indexed to body weight

  The primary outcome of the trial will be VO2peak indexed to body weight. (mL/kg/min). The data will be analyzed on an intention-to-treat basis comparing the outcomes across treatment arms (LoDoCo vs. placebo) using analysis of variance for repeated measures (ANOVA). Randomization of 60 participants (30 in LoDoCo vs. placebo) will provide \>80% power at a two-sided level of significance of 0.05 to detect a \>15% difference in VO2peak at the end of the study period. This estimate assumes a target population mean VO2peak of 10.5 ml/kg/min (SD 2.9) based on data from our local registry. Assuming a dropout rate of \~20%, we will plan to enroll 72 participants. We will also evaluate the association between changes in hs-CRP with changes in VO2peak across the entire cohort of participants using adjusted linear and logistic regression models

  Over 3 months

Secondary Outcomes (4)

• Difference in 6 minute walk distance

  3 months

• Difference in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ) Score

  3 months

• Percent change cardiac structure and function

  Baseline and 3 months

• Difference in hs-CRP levels

  3 months

Study Arms (2)

Low dose colchicine

EXPERIMENTAL

Low dose colchicine 0.5 mg once a day orally for 3 months

Drug: Low Dose Colchicine

Placebo

PLACEBO COMPARATOR

Placebo once a day orally for 3 months

Drug: Placebo

Interventions

Low Dose Colchicine DRUG

Colchicine has been demonstrated to improve cardiovascular outcomes among patients with cardiovascular disease. In the COLCOT trial, the use of low-dose colchicine resulted in a reduction of major adverse cardiovascular events among participants with recent MI. The trial demonstrated the utility of anti-inflammatory therapies in improving cardiovascular outcomes. Colchicine has been widely used for decades and its safety profile is well established.

Also known as: LoDoCo

Low dose colchicine

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Informed consent was obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• \. Age 50 years or above at the time of signing the informed consent. 3. Serum hs-CRP 2 mg/L at the time of baseline testing. 4. Diagnosis of chronic HFpEF within 6 months of enrolment must have one of the following:
• a. Structural Heart Disease with one of the following on echocardiography within 12 months of enrolment.
• i. LA volume index \> 34 ml/m2. ii. LA diameter ≥ 3.8 cm. iii. LA length ≥ 5.0 cm. iv. LA area ≥ 20 cm2. v. LA volume ≥ 55 mL. vi. Intraventricular septal thickness ≥1.1 cm. vii. Posterior wall thickness ≥1.1 cm. viii. LV mass index ≥115 g∕m2 in men or ≥ 95 g∕m2 in women. ix. E/e' (mean septal and lateral) ≥ 10. x. e' (mean septal and lateral) \< 9 cm/s b. Pulmonary capillary wedge pressure (PCWP) at rest³15 mmHg or Left ventricular end-diastolic pressure (LVEDP) ³18 mmHg, (PCWP) with exercise ³25 mmHg or (³ 2 mmHg/L/min) c. HF hospitalization or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to enrolment in combination with NT-proBNP ≥ 125 pg/mL within 1 month of enrolment for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening NT-proBNP must be ≥ 300 pg/mL 5. Ambulatory participants who can perform cardiopulmonary exercise testing. 6. Stable doses of HF-specific medications within the last 1 month. 7. Stable level of physical activity 8. Stable dose of any weight loss medications.

You may not qualify if:

• \. Renal impairment: eGFR \<30mL/min 4. Severe valvular heart disease is considered likely to require intervention. 5. Life expectancy \<1 year. 6. Unable to perform cardiopulmonary exercise testing. 7. ALT or AST \>2.5 ULN at time of screening

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Related Publications (20)

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  PMID: 35363499 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.

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  PMID: 34503685 BACKGROUND

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  PMID: 20447537 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.

  PMID: 30971818 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.

  PMID: 26682792 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.

  PMID: 21075869 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.

  PMID: 30114262 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.

  PMID: 28360225 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.

  PMID: 28100627 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.

  PMID: 28705911 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.

  PMID: 25605639 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.

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• 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.

  PMID: 20447574 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.

  PMID: 31779931 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.

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• 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.

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• 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.

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• 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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MeSH Terms

Conditions

Heart Failure; Inflammation

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Ambarish Pandey, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ambarish Pandey, MD

CONTACT

2146459762; ambarish.pandey@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: November 13, 2023
• Study Start: April 24, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)