Apolipoprotein CIII Reduction Via Colchicine

Early Phase 1

Completed

• Conditions: Gout; Pericarditis; Hypertriglyceridemia
• Interventions: Drug: Colchicine

• Registration Number: NCT02083510
• Lead Sponsor: Scripps Translational Science Institute

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).

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-03-05
• Study First Submitted QC: 2014-03-06
• Study First Posted: 2014-03-11
• Status Verified: 2014-05
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Last Update Submitted: 2014-05-28
• Last Update Posted: 2014-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Colchicine	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.

Primary Outcome Measures

Name	Time	Method
Reduction in ApoCIII levels	6 weeks
Reduction of triglycerides and very low density lipoprotein (VLDL) levels	6 weeks

Secondary Outcome Measures

Name	Time	Method
Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP)	6 weeks

Trial Locations

Locations (1)

Scripps Translational Science Institute; 🇺🇸 La Jolla, California, United States