Clinical trial NCT02035891: Low-dose Colchicine in Patients With Type 2 Diabetes Mellitus and Microalbuminuria
Official title: Low-dose Colchicine Intervention in Patients With Type 2 Diabetes Mellitus and Microalbuminuria: Chongqing Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Nephropathy
Keywords: colchicine
urinary albumin-to-creatinine ratio
carotid Intima-Media Thickness
overt nephropathy
Type 2 diabetes
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
First posted: 2014-01-14
Enrollment: 160
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. The primary objective of this study was： in patients with type 2 diabetes and microalbuminuria who have been receiving stable treatment of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) for at least 3 months, whether low-dose colchicine slows the progression of microvascular complications.
2. The secondary objective of this study was： (1) whether low-dose colchicine could reduce Urinary Albumin To Creatinine Ratio (UACR), or improve eGFR in patients with type 2 diabetes and microalbuminuria; (2) whether low-dose colchicine decreases carotid intima-media thickness(IMT) in patients with type 2 diabetes and microalbuminuria; (3) whether low-dose colchicine reduces the risk of cardiovascular events or mortality in patients with type 2 diabetes and microalbuminuria.

Detailed description: BACKGROUND-Previous study reported that colchicine 0.5 mg/day, in addition to statins and other standard secondary prevention therapies, was effective for the prevention of cardiovascular events in patients with stable coronary disease. An experiment conducted by Li et al. showed that twenty-four-hour urinary albumin excretion was reduced after 6 months colchicine treatment in rats with diabetic nephropathy.As both micro and macrovascular complications of diabetes are closely associated with inflammation,with the anti-inflammation property,colchicine might reduce risk for micro and macrovascular complications of diabetes.

STUDY DESIGN-Patients with type 2 diabetes and microalbuminuria(30mg/g Cr≤UACR≤300mg/g Cr) who have received stable dosage of ACEI/ARB for at least 3 months will be randomized to receive colchicine 0.5 mg/day or placebo.

This trial includes four phases:

* Phases 1: A prospective, randomized，double-blind, control study, aims at evaluating microvascular events from date of randomization until the third year. Other parameters included evaluating changes of UACR, eGFR, CIMT from baseline to the follow-up.
* Phases 2: A prospective observational study, aims at evaluating macrovascular and microvascular events from date of randomization until the 6th year.

SAFETY AND DATA MANAGEMENT-Independent Safety and Data Monitoring Committee has been set up to monitor the safety and tolerability of the subjects; this committee will analyze data independent of investigators at the end of any one phase.

Eligibility criteria: Inclusion Criteria:

* Well informed of the procedures of this trial and informed consent is obtained
* Voluntarily accept standardized treatment
* 30-70 years old, gender is not limited
* Diagnosed as type 2 diabetes and have received standardized hypoglycemic therapy
* Have been receiving stable doses of ACEI or ARBs for at least 3 months
* Two of three examinations of UACR at random urine are 30-300 mg/g Cr (infection or other factors were ruled out) in 3 months
* Well compliance
* Capable of self blood Glucose monitoring

Exclusion Criteria:

* Pregnant or lactating
* Type 1 diabetes
* Poor blood glucose control（HbA1c\>11%）
* A history of malignant tumor
* Abnormal liver or renal function (defined as alanine aminotransferase(ALT)\>2.5 times higher than normal range,or eGFR\<30 mL/min per 1•73 m²)
* Poor blood pressure control \[systolic blood pressure(SBP)\>180mmHg,or diastolic blood pressure(DBP)\>110mmHg\]
* With severe heart disease,cardiac function worse than grade II,anemia(Hb\<9.0g/d1)
* Continuous use of colchicine or non-steroidal anti-inflammatory drugs (except aspirin) more than one week in recent 3 months
* History of gout
* Blood routine test indicates that the white blood cell count(WBC) \<3\*109/l
* Body Mass Index(BMI)\<18.5 or ≥35kg/m2
* Drug or alcohol abuse
* Accompanying mental disorder who can't collaborate
* Abnormal digestion and absorption function
* Other endocrine diseases
* Other chronic diseases needed long-term glucocorticoid treatment
* With severe infection, immune dysfunction
* A history of colchicine allergies or allergic constitution

Primary outcomes:
measure: The incidence of overt nephropathy
timeFrame: 3 years
Secondary outcomes:
measure: The proportion of patients achieving at least a 15% reduction in UACR
timeFrame: 3 years
measure: Changes in estimated Glomerular Filtration Rate (eGFR)
timeFrame: 3 years
measure: The number of patients who have new or worsening diabetic neuropathy
timeFrame: 3 years
measure: The number of patients who have new or worsening diabetic retinopathy
timeFrame: 3 years
measure: changes in CIMT from baseline to the 3rd year
timeFrame: 18 months and 3 year
measure: The number of patients who have new cardiovascular events
timeFrame: 6 years
measure: changes of UACR
timeFrame: 6 years
measure: changes of eGFR
timeFrame: 6 years
measure: Death from any cause
timeFrame: 6 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: First Affiliated Hospital of Chongqing Medical University
name: Qifu Li, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013 Jan 29;61(4):404-410. doi: 10.1016/j.jacc.2012.10.027. Epub 2012 Dec 19.
citation: Nidorf M, Thompson PL. Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. Am J Cardiol. 2007 Mar 15;99(6):805-7. doi: 10.1016/j.amjcard.2006.10.039. Epub 2007 Jan 16.
citation: Navarro-Gonzalez JF, Mora-Fernandez C, Muros de Fuentes M, Garcia-Perez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011 Jun;7(6):327-40. doi: 10.1038/nrneph.2011.51. Epub 2011 May 3.
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citation: Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999 Feb 20;353(9153):617-22. doi: 10.1016/S0140-6736(98)07368-1.
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citation: Li JJ, Lee SH, Kim DK, Jin R, Jung DS, Kwak SJ, Kim SH, Han SH, Lee JE, Moon SJ, Ryu DR, Yoo TH, Han DS, Kang SW. Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy. Am J Physiol Renal Physiol. 2009 Jul;297(1):F200-9. doi: 10.1152/ajprenal.90649.2008. Epub 2009 Apr 15.