Apolipoprotein CIII Reduction Via Colchicine

Sponsor

Scripps Translational Science Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02083510

Collaborator

(none)

Enrollment

Location

Arm

2.9

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia Gout Pericarditis	Drug: Colchicine	Early Phase 1

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Feb 1, 2014

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Colchicine Other Names: Colcrys

Arm

Intervention/Treatment

Experimental: 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.

Drug: Colchicine

Other Names:

Colcrys

Outcome Measures

Primary Outcome Measures

Reduction in ApoCIII levels [6 weeks]
Reduction of triglycerides and very low density lipoprotein (VLDL) levels [6 weeks]

Secondary Outcome Measures

Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP) [6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

•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