A Translational Study to Understand the Mechanism of Apolipoprotein CIII Reduction Via Colchicine
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Reduction in ApoCIII levels
研究概览
简要总结
The aim of this trial will be to determine an effect-size for the administration of chronic low-dose colchicine in the reduction of serum levels of triglycerides (TG), very-low density lipoproteins (VLDL), and apolipoprotein CIII (apoCIII) in human subjects over a period of 4-6 weeks.
详细描述
The aim of this proposal will be to show, in a translational fashion, a relationship between colchicine and reduction of factors affecting triglyceride metabolism, especially apoCIII and VLDL levels. We envision colchicine as playing a role in identifying and elucidating a new mechanism for lowering TG levels, which may have a great impact on targeting patients who have not met non-HDL goals according to Adult Treatment Panel III (ATPIII guidelines) or at risk for hypertriglyceridemia-induced pancreatitis [11]. We will accomplish this by conducting a prospective cohort clinical trial of low-dose colchicine in hypertriglyceridemic patients to assess percent (%) reduction of apoCIII, VLDL, and TG. Secondary endpoints will be to observe the effects of colchicine on apoA, apoB, HDL, low-density lipoprotein (LDL), and total cholesterol (TC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Acute new-onset pericarditis or recurrent pericarditis (≥2 following criteria)
- •Sharp and pleuritic chest pain improved or relieved by sitting up and leaning forward
- •A pericardial friction rub
- •Electrocardiogram (EKG) findings of diffuse ST-segment elevations or PR depression
- •New or worsening pericardial effusion visualized on echocardiogram.
- •Acute gouty arthritis (according to the ACR; ≥1 of following criteria:
- •Joint fluid containing urate crystals
- •Tophus proved to contain urate crystals by chemical means
- •Polarized light microscopy
- •Presence of six of the following in the absence of crystal identification:
- •>1 attack of acute arthritis
- •Maximum inflammation developed in 1 day
- •Monoarthritis attack
- •Redness observed over joints
- •1st metatarsal joint painful or swollen
- •Unilateral 1st metatarsal joint attack
- •Unilateral tarsal joint attack
- •Tophus (suspected)
- •Hyperuricemia
- •Asymmetric swelling within a joint visible on physical examination or radiography
- •Subcortical cysts without erosions visible on radiography
- •Monosodium urate monohydrate microcrystals in joint fluid during attack
- •Joint fluid culture negative for organisms during attack.
- •If N < 10 after 3 weeks of trial initiation, then employ enrollment strategy #2
- •Enrollment strategy #2:
- •History of hypertriglyceridemia (TG ≥ 150 mg/dL) AND
- •Age ≥ 18 years old
- •Capable of providing informed consent
- •Capable of taking Colchicine 0.6-1.2 mg/day orally for 6 weeks
- •Capable of providing a blood sample
排除标准
- •Colchicine use < 8 weeks from baseline VAP panel
- •Pregnant or female of child bearing age
- •On corticosteroid therapy or corticosteroid use < 4 weeks from baseline VAP panel
- •History of statin myopathy or hepatotoxicity
- •History of colchicine intolerance or hypersensitivity
- •Severe end-stage renal disease (eGFR ≤ 20 mL/min/1.73 m2) or requiring dialysis
- •Hepatic Impairment (Child-Pugh class B or C)
- •Myopericarditis (If TnI is elevated on presentation of acute pericarditis)
- •Inflammatory Bowel Disease
- •Tuberculous, neoplastic, or purulent pericarditis
研究组 & 干预措施
Colchicine
Patients will be enrolled with either gout/pericarditis or hypertriglyceridemia, have VAP and Apolipoprotein CIII levels at baseline, administer Colchicine for 6 weeks with reassessment of Apolipoprotein CIII and VAP.
干预措施: Colchicine (Drug)
结局指标
主要结局
Reduction in ApoCIII levels
时间窗: 6 weeks
Reduction of triglycerides and very low density lipoprotein (VLDL) levels
时间窗: 6 weeks
次要结局
- Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP)(6 weeks)
研究者
Peter G. Schultz, PhD
Prinicpal Investigator
The Scripps Research Institute