Heart FailurePhase 2NCT06130059
Efficacy of LoDoCo in Improving Exercise Capacity Among Patients With HFpEF and Inflammation
A Phase 2 study testing Low Dose Colchicine in people with Heart Failure and Inflammation, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Heart Failure, Inflammation
- What is being tested?
- Low Dose Colchicine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2024to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 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.
- 2. 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:
- Structural Heart Disease with one of the following on echocardiography within 12 months of enrolment.
- 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.
Who cannot join
- 1. Do not otherwise meet the inclusion criteria. 2. Women who are pregnant, breastfeeding, or may be considering pregnancy during the study period.
- 3. 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75235
Ambarish Pandey, MD, 214-645-9762, ambarish.pandey@utsouthwestern.edu
About this study
Official title: Pilot Study to Evaluate the Efficacy of Low Dose Colchicine (LoDoCo ®) to Improve Exercise Capacity Among Patients With Chronic Stable HFpEF and Systemic Inflammation
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.
Read the detailed description
The investigators propose a single-center, double-blind placebo-controlled pilot study of LoDoCo vs. matching placebo among patients with chronic stable HFpEF and systemic inflammation. Patients that meet the eligibility criteria will be recruited prospectively from the UT Southwestern HFpEF program. Outcomes of interest will be assessed at baseline and 3 months. The primary outcome of the trial will be VO2peak indexed to body weight, and key secondary outcomes will include - 6MWD, KCCQ, change in structure and functional parameters of heart and hs-CRP levels.
Study Site:
UT Southwestern HFpEF program: The UT Southwestern HFpEF program, established in 2021 and is an integrated clinical and research enterprise that is responsible for the clinical care of patients with HFpEF and receives internal referrals from primary care, hospital medicine, geriatrics, and cardiology within the UT Southwestern health system and from clinics and hospitals in Texas and neighboring states. In the last year, the clinic has received over 300 referrals. The clinical program is integrated with an active research program that focuses on the phenotypic characterization of patients with HFpEF with an emphasis on exercise phenotyping. All patients with suspicion of HFpEF have a detailed laboratory, invasive hemodynamic, echocardiographic, and cardiopulmonary exercise testing. An active registry of patients is maintained which currently has ~150 participants with an established diagnosis of HFpEF and detailed phenotyping assessment.
The HFpEF clinic will serve as the clinical site of the study. Dr. Ambarish Pandey (PI) serves as the medical director of the HFpEF program.
Recruitment:
Detailed eligibility criteria are listed below. Participants will be drawn from the UT Southwestern HFpEF registry. The target enrollment for the study is 60 participants. Historical records and baseline evaluations will be used to determine eligibility for the study. After informed consent, participants will undergo study assessments as listed below followed by randomization.
Study Assessments (screening ):
Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Blood tests: Routine blood tests including creatinine, liver function tests, hemoglobin, hematocrit, serum chemistries, hs-CRP, and NT-proBNP. Blood assessments will be performed at the time of the baseline visit and 3-months post-treatment. (30 ml blood will be collected in the whole study)
Baseline and randomization (within 2 weeks of screening) Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Echocardiography: Echocardiography (ultrasound tests) of the heart before and after exercise and submaximal handgrip will be performed at baseline and follow-up. This is a non-invasive procedure in which the examination will be performed during supine rest to obtain standard two-dimensional images in the parasternal long and short axis and the apical two and four heart chamber views. To take pictures of patient's heart, a small non-invasive scanning probe with gel that will be applied to the participant's chest. Small adhesive pads will also be placed with wires to measure the participant's heart rate. It is anticipated that this procedure will not take more than 1 hour.
6-minute walking distance: The 6MWD assesses the distance a participant can walk in six minutes. It is a direct and timed measure of walking ability, which is technically simple, reproducible, and when administrators. are well trained, and readily standardized. The goal is for the subject to walk as far as possible in six minutes without running. The subject can self-pace and rest as needed as the subjects traverse back and forth along a marked walkway of 66 feet (20 m).
Kansas City Cardiomyopathy Questionnaire: (KCCQ): KCCQ measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. The approximate completion time is 4-6 minutes. Scores range from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health-related quality of life, respectively. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. The questionnaire consists of 23 items yielding:
7 domain scores (score range):
- Physical limitation (0-100)
- Symptom frequency (0-100)
- Symptom severity (0-100)
- Symptom stability (0-100)
- Self-efficacy and knowledge (0-100)
- Quality of life (0-100)
- Social limitation (0-100) 2 summary scores (score range):
- Total symptom score (0-100)
- Clinical summary score (CSS) (0-100) Overall summary score (score range: 0-100).
Cardiopulmonary Exercise testing: VO2peak, Participants will perform a maximal stress test on the upright cycle ergometer (Lode Corival CPET, Groningen, Netherlands). Participants will perform a continuous ramp protocol with a continuous increase in workload until maximal exhaustion. Respiratory gases including oxygen and carbon dioxide will be measured continuously using a metabolic cart (Ultima™ CardioO2 ® gas exchange analysis system; Saint Paul, Minnesota, USA) with measurements of expired oxygen and carbon dioxide and analyzed using Breeze Suit (Saint Paul, Minnesota, USA). The study team will determine maximal heart rate, peak oxygen uptake (VO2), carbon dioxide production (VCO2), pulmonary ventilation (VE), ventilatory equivalents for oxygen (VE/VO2), carbon dioxide (VE/CO2), respiratory exchange ratio (RER), end-tidal partial pressure of oxygen (PETO2), and carbon dioxide (PETCO2). Assessments will be performed at the time of the baseline visit, and 3 months post-treatment.
Randomization:
After review of baseline assessments. Qualifying Participants will be randomized to active study drug or matching placebo using a 1:1 block randomization scheme. The investigational drug service at UT Southwestern will store the study drug, perform randomization, and dispense the investigational product. Both participants and the study team will be blinded to treatment assignment.
3 months
Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Blood tests: Routine blood tests including creatinine, liver function tests, hemoglobin, hematocrit, serum chemistries, hs-CRP, and NT-proBNP. Blood assessments will be performed at the time of the baseline visit and 3-months post-treatment. (30 ml blood will be collected in the whole study)
Echocardiography: Echocardiography (ultrasound tests) of the heart before and after exercise and submaximal handgrip will be performed. This is a non-invasive procedure in which the examination will be performed during supine rest to obtain standard two-dimensional images in the parasternal long and short axis and the apical two and four heart chamber views. To take pictures of patient's heart, a small non-invasive scanning probe with gel that will be applied to the participant's chest. Small adhesive pads will also be placed with wires to measure the participant's heart rate. It is anticipated that this procedure will not take more than 1 hour.
6-minute walking distance: The 6MWD assesses the distance a participant can walk in six minutes. It is a direct and timed measure of walking ability, which is technically simple, reproducible, and when administrators. are well trained, and readily standardized. The goal is for the subject to walk as far as possible in six minutes without running. The subject can self-pace and rest as needed as the subjects traverse back and forth along a marked walkway of 66 feet (20 m).
Kansas City Cardiomyopathy Questionnaire: (KCCQ): KCCQ measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. The approximate completion time is 4-6 minutes. Scores range from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health-related quality of life, respectively. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. The questionnaire consists of 23 items yielding:
7 domain scores (score range):
- Physical limitation (0-100)
- Symptom frequency (0-100)
- Symptom severity (0-100)
- Symptom stability (0-100)
- Self-efficacy and knowledge (0-100)
- Quality of life (0-100)
- Social limitation (0-100) 2 summary scores (score range):
- Total symptom score (0-100)
- Clinical summary score (CSS) (0-100) Overall summary score (score range: 0-100).
Cardiopulmonary Exercise testing: VO2peak, Participants will perform a maximal stress test on the upright cycle ergometer (Lode Corival CPET, Groningen, Netherlands). Participants will perform a continuous ramp protocol with a continuous increase in workload until maximal exhaustion. Respiratory gases including oxygen and carbon dioxide will be measured continuously using a metabolic cart (Ultima™ CardioO2 ® gas exchange analysis system; Saint Paul, Minnesota, USA) with measurements of expired oxygen and carbon dioxide and analyzed using Breeze Suit (Saint Paul, Minnesota, USA). The study team will determine maximal heart rate, peak oxygen uptake (VO2), carbon dioxide production (VCO2), pulmonary ventilation (VE), ventilatory equivalents for oxygen (VE/VO2), carbon dioxide (VE/CO2), respiratory exchange ratio (RER), end-tidal partial pressure of oxygen (PETO2), and carbon dioxide (PETCO2). Assessments will be performed at the time of the baseline visit, and 3 months post-treatment.
- Conditions
- Heart Failure, Inflammation
- Being tested
- Low Dose Colchicine, Placebo
- Medical subject headings
- Heart Failure, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose ColchicineDrug
Also called LoDoCo
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Low dose colchicine | Experimental | Low dose colchicine 0.5 mg once a day orally for 3 months Receives: Drug: Low Dose Colchicine |
| Placebo | Placebo comparator | Placebo once a day orally for 3 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Over 3 months
Secondary outcomes (4)
Difference in 6 minute walk distance
It will be assessed using analysis of covariance (ANCOVA). The randomized arm will be the between-subject grouping variable; covariates will be baseline value, baseline age, sex, and hs-CRP. The least-square means will be used to estimate intervention effects. Tests will be conducted at the 5% two-sided level of significance. The appropriate transformation will be used for biomarkers with skewed distributions to stabilize variance and achieve better approximation to normality.
Measured: 3 months
Difference in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ) Score
It will be assessed using analysis of covariance (ANCOVA). The randomized arm will be the between-subject grouping variable; covariates will be baseline value, baseline age, sex, and hs-CRP. The least-square means will be used to estimate intervention effects. Tests will be conducted at the 5% two-sided level of significance. The appropriate transformation will be used for biomarkers with skewed distributions to stabilize variance and achieve better approximation to normality. Scores range from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health-related quality of life, respectively.
Measured: 3 months
Percent change cardiac structure and function
Echocardiography at baseline and follow-up will be used to determine changes in cardiac structure and function. Left atrial, and ventricular sizes will be measured at end-diastole and end-systole. Cardiac systolic function will be measured using left ventricular ejection fraction. Diastolic function will be measured as tissue Doppler velocities - E/e', and e' velocities. Absolute, and percent changes in these parameters between baseline and follow-up will be measured as an exploratory outcome. Analysis of covariance (ANCOVA) will be used for the analysis of the effect of the intervention. The randomized arm will be the between-subject grouping variable; covariates will be baseline value, baseline age, sex The least-square means will be used to estimate intervention effects.
Measured: Baseline and 3 months
Difference in hs-CRP levels
It will be assessed using analysis of covariance (ANCOVA). The randomized arm will be the between-subject grouping variable; covariates will be baseline value, baseline age, sex, and hs-CRP. The least-square means will be used to estimate intervention effects. Tests will be conducted at the 5% two-sided level of significance. The appropriate transformation will be used for biomarkers with skewed distributions to stabilize variance and achieve better approximation to normality.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start24 Apr 2024
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ambarish Pandey, University of Texas Southwestern Medical Center
- Investigators
- Ambarish Pandey, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06130059
- Sponsor's protocol ID
- STU-2023-0964
- Status last verified
- Feb 2026
- First submitted
- 24 Oct 2023
- Last updated
- 27 Feb 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 35363499Nayor 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.
PubMed 32535122Pandey 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.
PubMed 34503685Kalogeropoulos 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.
PubMed 20447537Schiattarella 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.
PubMed 30971818Franssen 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.
PubMed 26682792Westermann 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.
PubMed 21075869DuBrock 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.
PubMed 30114262Tromp 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.
PubMed 28360225Hage 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.
PubMed 28100627Kitzman 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.
PubMed 28705911Fleg 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.
PubMed 25605639Warraich 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.
PubMed 30571197Chiarantini 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.
PubMed 20447574Pandey 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.
PubMed 31779931
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate the Efficacy of Low Dose Colchicine (LoDoCo ®) to Improve Exercise Capacity Among Patients With Chronic Stable HFpEF and Systemic Inflammation
- ClinicalTrials.gov ID
- NCT06130059
- Acronym / sponsor ID
- STU-2023-0964
- Conditions
- Heart Failure, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 24 Apr 2024 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 13 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators propose a single-center, double-blind placebo-controlled pilot study of LoDoCo vs. matching placebo among patients with chronic stable HFpEF and systemic inflammation. Patients that meet the eligibility criteria will be recruited prospectively from the UT Southwestern HFpEF program. Outcomes of interest will be assessed at baseline and 3 months. The primary outcome of the trial will be VO2peak indexed to body weight, and key secondary outcomes will include - 6MWD, KCCQ, change in structure and functional parameters of heart and hs-CRP levels.
Study Site:
UT Southwestern HFpEF program: The UT Southwestern HFpEF program, established in 2021 and is an integrated clinical and research enterprise that is responsible for the clinical care of patients with HFpEF and receives internal referrals from primary care, hospital medicine, geriatrics, and cardiology within the UT Southwestern health system and from clinics and hospitals in Texas and neighboring states. In the last year, the clinic has received over 300 referrals. The clinical program is integrated with an active research program that focuses on the phenotypic characterization of patients with HFpEF with an emphasis on exercise phenotyping. All patients with suspicion of HFpEF have a detailed laboratory, invasive hemodynamic, echocardiographic, and cardiopulmonary exercise testing. An active registry of patients is maintained which currently has ~150 participants with an established diagnosis of HFpEF and detailed phenotyping assessment.
The HFpEF clinic will serve as the clinical site of the study. Dr. Ambarish Pandey (PI) serves as the medical director of the HFpEF program.
Recruitment:
Detailed eligibility criteria are listed below. Participants will be drawn from the UT Southwestern HFpEF registry. The target enrollment for the study is 60 participants. Historical records and baseline evaluations will be used to determine eligibility for the study. After informed consent, participants will undergo study assessments as listed below followed by randomization.
Study Assessments (screening ):
Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Blood tests: Routine blood tests including creatinine, liver function tests, hemoglobin, hematocrit, serum chemistries, hs-CRP, and NT-proBNP. Blood assessments will be performed at the time of the baseline visit and 3-months post-treatment. (30 ml blood will be collected in the whole study)
Baseline and randomization (within 2 weeks of screening) Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Echocardiography: Echocardiography (ultrasound tests) of the heart before and after exercise and submaximal handgrip will be performed at baseline and follow-up. This is a non-invasive procedure in which the examination will be performed during supine rest to obtain standard two-dimensional images in the parasternal long and short axis and the apical two and four heart chamber views. To take pictures of patient's heart, a small non-invasive scanning probe with gel that will be applied to the participant's chest. Small adhesive pads will also be placed with wires to measure the participant's heart rate. It is anticipated that this procedure will not take more than 1 hour.
6-minute walking distance: The 6MWD assesses the distance a participant can walk in six minutes. It is a direct and timed measure of walking ability, which is technically simple, reproducible, and when administrators. are well trained, and readily standardized. The goal is for the subject to walk as far as possible in six minutes without running. The subject can self-pace and rest as needed as the subjects traverse back and forth along a marked walkway of 66 feet (20 m).
Kansas City Cardiomyopathy Questionnaire: (KCCQ): KCCQ measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. The approximate completion time is 4-6 minutes. Scores range from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health-related quality of life, respectively. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. The questionnaire consists of 23 items yielding:
7 domain scores (score range):
- Physical limitation (0-100)
- Symptom frequency (0-100)
- Symptom severity (0-100)
- Symptom stability (0-100)
- Self-efficacy and knowledge (0-100)
- Quality of life (0-100)
- Social limitation (0-100) 2 summary scores (score range):
- Total symptom score (0-100)
- Clinical summary score (CSS) (0-100) Overall summary score (score range: 0-100).
Cardiopulmonary Exercise testing: VO2peak, Participants will perform a maximal stress test on the upright cycle ergometer (Lode Corival CPET, Groningen, Netherlands). Participants will perform a continuous ramp protocol with a continuous increase in workload until maximal exhaustion. Respiratory gases including oxygen and carbon dioxide will be measured continuously using a metabolic cart (Ultima™ CardioO2 ® gas exchange analysis system; Saint Paul, Minnesota, USA) with measurements of expired oxygen and carbon dioxide and analyzed using Breeze Suit (Saint Paul, Minnesota, USA). The study team will determine maximal heart rate, peak oxygen uptake (VO2), carbon dioxide production (VCO2), pulmonary ventilation (VE), ventilatory equivalents for oxygen (VE/VO2), carbon dioxide (VE/CO2), respiratory exchange ratio (RER), end-tidal partial pressure of oxygen (PETO2), and carbon dioxide (PETCO2). Assessments will be performed at the time of the baseline visit, and 3 months post-treatment.
Randomization:
After review of baseline assessments. Qualifying Participants will be randomized to active study drug or matching placebo using a 1:1 block randomization scheme. The investigational drug service at UT Southwestern will store the study drug, perform randomization, and dispense the investigational product. Both participants and the study team will be blinded to treatment assignment.
3 months
Physical exam and vitals: Height, Weight and vitals - blood pressure, heart rate and SpO2 will be measured
Blood tests: Routine blood tests including creatinine, liver function tests, hemoglobin, hematocrit, serum chemistries, hs-CRP, and NT-proBNP. Blood assessments will be performed at the time of the baseline visit and 3-months post-treatment. (30 ml blood will be collected in the whole study)
Echocardiography: Echocardiography (ultrasound tests) of the heart before and after exercise and submaximal handgrip will be performed. This is a non-invasive procedure in which the examination will be performed during supine rest to obtain standard two-dimensional images in the parasternal long and short axis and the apical two and four heart chamber views. To take pictures of patient's heart, a small non-invasive scanning probe with gel that will be applied to the participant's chest. Small adhesive pads will also be placed with wires to measure the participant's heart rate. It is anticipated that this procedure will not take more than 1 hour.
6-minute walking distance: The 6MWD assesses the distance a participant can walk in six minutes. It is a direct and timed measure of walking ability, which is technically simple, reproducible, and when administrators. are well trained, and readily standardized. The goal is for the subject to walk as far as possible in six minutes without running. The subject can self-pace and rest as needed as the subjects traverse back and forth along a marked walkway of 66 feet (20 m).
Kansas City Cardiomyopathy Questionnaire: (KCCQ): KCCQ measures Health-Related Quality of Life (HRQOL) and is a disease-specific health status instrument for HF. The approximate completion time is 4-6 minutes. Scores range from 0 to 100, with 0 as the lowest score and 100 as the highest score. Higher scores indicate better health status, fewer symptoms, and greater disease-specific health-related quality of life, respectively. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. The questionnaire consists of 23 items yielding:
7 domain scores (score range):
- Physical limitation (0-100)
- Symptom frequency (0-100)
- Symptom severity (0-100)
- Symptom stability (0-100)
- Self-efficacy and knowledge (0-100)
- Quality of life (0-100)
- Social limitation (0-100) 2 summary scores (score range):
- Total symptom score (0-100)
- Clinical summary score (CSS) (0-100) Overall summary score (score range: 0-100).
Cardiopulmonary Exercise testing: VO2peak, Participants will perform a maximal stress test on the upright cycle ergometer (Lode Corival CPET, Groningen, Netherlands). Participants will perform a continuous ramp protocol with a continuous increase in workload until maximal exhaustion. Respiratory gases including oxygen and carbon dioxide will be measured continuously using a metabolic cart (Ultima™ CardioO2 ® gas exchange analysis system; Saint Paul, Minnesota, USA) with measurements of expired oxygen and carbon dioxide and analyzed using Breeze Suit (Saint Paul, Minnesota, USA). The study team will determine maximal heart rate, peak oxygen uptake (VO2), carbon dioxide production (VCO2), pulmonary ventilation (VE), ventilatory equivalents for oxygen (VE/VO2), carbon dioxide (VE/CO2), respiratory exchange ratio (RER), end-tidal partial pressure of oxygen (PETO2), and carbon dioxide (PETCO2). Assessments will be performed at the time of the baseline visit, and 3 months post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose colchicine | Experimental | Drug: Low Dose ColchicineLow dose colchicine 0.5 mg once a day orally for 3 months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo once a day orally for 3 months |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 1. 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.
- 2. 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:
Key exclusion criteria (2 listed)
- 1. Do not otherwise meet the inclusion criteria. 2. Women who are pregnant, breastfeeding, or may be considering pregnancy during the study period.
- 3. 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose ColchicineAlso: LoDoCoColchicine 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. | Drug | Low dose colchicine |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Peak VO2 indexed to body weight
Time frame: Over 3 months
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
4 secondary outcomes
Difference in 6 minute walk distance
Time frame: 3 months
Difference in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ) Score
Time frame: 3 months
Percent change cardiac structure and function
Time frame: Baseline and 3 months
Difference in hs-CRP levels
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Background: PubMed 35363499Heidenreich 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: PubMed 32535122Nayor 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: PubMed 34503685Pandey 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: PubMed 20447537Kalogeropoulos 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: PubMed 30971818Schiattarella 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: PubMed 26682792Franssen 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: PubMed 21075869Westermann 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: PubMed 30114262DuBrock 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: PubMed 28360225Tromp 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: PubMed 28100627Hage 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: PubMed 28705911Kitzman 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: PubMed 25605639Fleg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ambarish Pandey, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose Colchicine in people with Heart Failure and Inflammation, run by University of Texas Southwestern Medical Center at 1 site in United States.
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 4 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 27 Feb 2026. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ambarish Pandey, MD (2146459762, ambarish.pandey@utsouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak VO2 indexed to body weight (time frame: Over 3 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 NCT06130059, which also lists 20 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 27 Feb 2026.