Pilot Study to Evaluate the Efficacy of Low Dose Colchicine (LoDoCo ®) to Improve Exercise Capacity Among Patients With Chronic Stable HFpEF and Systemic Inflammation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Peak VO2 indexed to body weight
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Serum hs-CRP 2 mg/L at the time of baseline testing.
- •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/m
- •ii. LA diameter ≥ 3.8 cm. iii. LA length ≥ 5.0 cm. iv. LA area ≥ 20 cm
- •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) ≥
- •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
- •Ambulatory participants who can perform cardiopulmonary exercise testing.
- •Stable doses of HF-specific medications within the last 1 month.
- •Stable level of physical activity
- •Stable dose of any weight loss medications.
排除标准
- •Do not otherwise meet the inclusion criteria.
- •Women who are pregnant, breastfeeding, or may be considering pregnancy during the study period.
- •Renal impairment: eGFR <30mL/min
- •Severe valvular heart disease is considered likely to require intervention.
- •Life expectancy <1 year.
- •Unable to perform cardiopulmonary exercise testing.
- •ALT or AST >2.5 ULN at time of screening
研究组 & 干预措施
Low dose colchicine
Low dose colchicine 0.5 mg once a day orally for 3 months
干预措施: Low Dose Colchicine (Drug)
Placebo
Placebo once a day orally for 3 months
干预措施: Placebo (Drug)
结局指标
主要结局
Peak VO2 indexed to body weight
时间窗: 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
次要结局
- 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)
研究者
Ambarish Pandey
Associate professor
University of Texas Southwestern Medical Center