Apolipoprotein CIII Reduction Via Colchicine

Condition(s) targeted: Hypertriglyceridemia; Gout; Pericarditis

Intervention: Colchicine (Drug)

Phase: Phase 0

Status: Completed

Sponsored by: Scripps Translational Science Institute

Official(s) and/or principal investigator(s):
Peter Schultz, PhD, Principal Investigator, Affiliation: Scripps Translational Science Institute

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.

Official title: A Translational Study to Understand the Mechanism of Apolipoprotein CIII Reduction Via Colchicine

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome:

Reduction in ApoCIII levels

Reduction of triglycerides and very low density lipoprotein (VLDL) levels

Secondary outcome: Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP)

Detailed description: 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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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.

OR •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

Exclusion Criteria:

- 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

Scripps Translational Science Institute, La Jolla, California 92037, United States

Starting date: February 2014
Last updated: May 28, 2014