Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial.

HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss.

HU6是一种新型的受控代谢加速器，它增强了线粒体解耦联，导致代谢增加和特定于脂肪的减重。

Background

To assess efficacy and safety of HU6 in reducing body weight, improving peak volume of oxygen consumption (VO2) and body composition among patients with obesity-related HFpEF.

评估HU6在减轻体重、改善峰值氧耗量（VO2）和身体成分方面对肥胖相关射血分数保留心力衰竭（HFpEF）患者的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: The Exploratory Phase 2A, Double-Blind, Placebo-ControlledDose Escalation Study of Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of HU6 for Subjects With Obese HFpEF (HuMAIN-HFpEF) trial was a multicenter, dose-escalation randomized clinical trial among patients with chronic stable HFpEF and obesity.

设计、设置和参与者：HuMAIN-HFpEF试验是一项多中心、剂量递增的随机临床试验，旨在评估肥胖HFpEF患者使用HU6的安全性、耐受性、药效学和药代动力学。这是一个探索性2A期、双盲、安慰剂对照的剂量递增研究。

Data were analyzed from July to October 2024.

数据分析时间为2024年7月至10月。

intervention

HU6 treatment for 19 weeks, starting at 150 mg per day and potentially up titrated to 450 mg per day based on safety and tolerability vs placebo.

HU6治疗持续19周，起始剂量为每天150毫克，根据安全性和耐受性可能上调至每天450毫克，与安慰剂进行比较。

main_outcomes_and_measures

The primary end point was change in body weight.

主要终点是体重的变化。

Results

Of 66 participants randomized (mean [SD] age, 64.5 [12] years; 38 female [58%]; mean [SD] weight, 110.9 [22.4] kg), 56 completed the trial. HU6 (vs placebo) significantly decreased weight (between-group difference, -2.86 kg; 95% CI, -4.68 to -1.04 kg; P = .003), total fat mass (between-group difference, -2.96 kg; 95% CI, -4.50 to -1.42 kg; P < .001), and percentage visceral fat (between-group difference,-1.3%; 95% CI, -2.1 to -0.5%; P = .003), with no significant loss of muscle mass.

在随机分配的66名参与者中（平均[标准差]年龄为64.5[12]岁；38名女性[58%]；平均[标准差]体重为110.9[22.4]公斤），有56人完成了试验。

There were no statistically significant changes in peak VO2, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire score, high-sensitivity C-reactive protein level, N-terminal pro-brain natriuretic peptide level, or diastolic function.

在峰值VO2、6分钟步行距离、堪萨斯城心肌病问卷评分、高敏C反应蛋白水平、N末端前脑钠肽水平或舒张功能方面，未观察到统计学上显著的变化。

Serious adverse events were noted in 5 participants (4 in the HU6 group; 1 in the placebo group), including 1 death, all judged unrelated to treatment.

在5名参与者中观察到严重不良事件（HU6组4人；安慰剂组1人），包括1例死亡，所有这些都被判断与治疗无关。

conclusions_and_relevance

Among patients with obesity-related HFpEF, treatment with HU6 for 19 weeks led to modest but statistically significant weight loss without significant changes in peak VO2.

在肥胖相关的心脏射血分数保留心力衰竭（HFpEF）患者中，接受HU6治疗19周后，体重适度但统计学上显著下降，而峰值VO2没有显著变化。

Larger trials of longer duration are warranted to determine whether longer-term administration of HU6 can improve exercise function, quality of life, and cardiovascular outcomes in this increasingly common disorder.

为了确定长期使用HU6是否能改善这种日益常见疾病的运动功能、生活质量以及心血管结果，有必要进行更大规模、更长期的试验。

trial_registration

ClinicalTrials.gov Identifier: NCT05284617.

临床试验注册号：NCT05284617。