Apolipoprotein CIII Reduction Via Colchicine

Study Overview
=================
Brief Summary
-----------------
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.

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).

Official Title
-----------------
A Translational Study to Understand the Mechanism of Apolipoprotein CIII Reduction Via Colchicine

Conditions
-----------------
Hypertriglyceridemia, Gout, Pericarditis

Intervention / Treatment
-----------------
* Drug: Colchicine


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>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. | Drug: Colchicine<br> <br> * Other names: Colcrys;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in ApoCIII levels |  | 6 weeks | 
| Reduction of triglycerides and very low density lipoprotein (VLDL) levels |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP) |  | 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colchicine, Hypertriglyceridemia, Apolipoprotein CIII