Clinical trial NCT02083510: Apolipoprotein CIII Reduction Via Colchicine
Official title: A Translational Study to Understand the Mechanism of Apolipoprotein CIII Reduction Via Colchicine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hypertriglyceridemia
Gout
Pericarditis
Keywords: Colchicine
Hypertriglyceridemia
Apolipoprotein CIII
Lead sponsor: Scripps Translational Science Institute
Sponsor class: OTHER
First posted: 2014-03-11
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).

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

Primary outcomes:
measure: Reduction in ApoCIII levels
timeFrame: 6 weeks
measure: Reduction of triglycerides and very low density lipoprotein (VLDL) levels
timeFrame: 6 weeks
Secondary outcomes:
measure: Measurement of Apolipoprotein A and Apolipoprotein B via Vertical Auto Profile (VAP)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Translational Science Institute
state: California
Study officials:
affiliation: Scripps Translational Science Institute
name: Peter Schultz, PhD
role: PRINCIPAL_INVESTIGATOR
References: