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Low-dose Colchicine in Patients With Type 2 Diabetes Mellitus and Microalbuminuria

Primary Purpose

Diabetic Nephropathy

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
colchicine 0.5mg/d
placebo 0.5mg/d
Sponsored by
Chongqing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Nephropathy focused on measuring colchicine, urinary albumin-to-creatinine ratio, carotid Intima-Media Thickness, overt nephropathy, Type 2 diabetes

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The First Affiliated Hospital of Chongqing Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

colchicine

placebo

Arm Description

0.5mg/d colchicine

appearance is same as colchicine

Outcomes

Primary Outcome Measures

The incidence of overt nephropathy
overt nephropathy is defined as any one of the events described below: （1） UACR greater than 300 mg/g Cr; (2) 24 h urinary albumin greater than 300 mg; (3)doubling of the serum creatinine level to at least 200 μmol per liter; (4)the need for renal-replacement therapy;(5) death due to renal disease.

Secondary Outcome Measures

The proportion of patients achieving at least a 15% reduction in UACR
Renal outcome
Changes in estimated Glomerular Filtration Rate (eGFR)
Renal outcome
The number of patients who have new or worsening diabetic neuropathy
diabetic neuropathy was assessed based on biothesiometer.
The number of patients who have new or worsening diabetic retinopathy
Diabetic retinopathy was diagnosed according to the six-level grading scale of the European Community- funded Concerted Action Programme into the Epidemiology and Prevention of Diabetes (EURODIAB)
changes in CIMT from baseline to the 3rd year
cardiovascular outcome
The number of patients who have new cardiovascular events
cardiovascular events include death from cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention or revascularization for peripheral atherosclerotic arterial disease, and amputation because of ischemia
changes of UACR
evaluated at 6, 12, 18, 24, 36, 48, 60, 72 months
changes of eGFR
evaluated at 6, 12, 18, 24, 36, 48, 60, 72 months
Death from any cause
All-cause mortality

Full Information

First Posted
January 4, 2014
Last Updated
January 29, 2019
Sponsor
Chongqing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT02035891
Brief Title
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

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 2013 (Actual)
Primary Completion Date
September 2019 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chongqing Medical University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
Keywords
colchicine, urinary albumin-to-creatinine ratio, carotid Intima-Media Thickness, overt nephropathy, Type 2 diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
colchicine
Arm Type
Active Comparator
Arm Description
0.5mg/d colchicine
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
appearance is same as colchicine
Intervention Type
Drug
Intervention Name(s)
colchicine 0.5mg/d
Intervention Description
on the basis of standard therapy to manage hyperglycemia, hypertension,dislipidemia etc.
Intervention Type
Drug
Intervention Name(s)
placebo 0.5mg/d
Intervention Description
on the basis of standard therapy to manage hyperglycemia, hypertension,dislipidemia etc.
Primary Outcome Measure Information:
Title
The incidence of overt nephropathy
Description
overt nephropathy is defined as any one of the events described below: （1） UACR greater than 300 mg/g Cr; (2) 24 h urinary albumin greater than 300 mg; (3)doubling of the serum creatinine level to at least 200 μmol per liter; (4)the need for renal-replacement therapy;(5) death due to renal disease.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
The proportion of patients achieving at least a 15% reduction in UACR
Description
Renal outcome
Time Frame
3 years
Title
Changes in estimated Glomerular Filtration Rate (eGFR)
Description
Renal outcome
Time Frame
3 years
Title
The number of patients who have new or worsening diabetic neuropathy
Description
diabetic neuropathy was assessed based on biothesiometer.
Time Frame
3 years
Title
The number of patients who have new or worsening diabetic retinopathy
Description
Diabetic retinopathy was diagnosed according to the six-level grading scale of the European Community- funded Concerted Action Programme into the Epidemiology and Prevention of Diabetes (EURODIAB)
Time Frame
3 years
Title
changes in CIMT from baseline to the 3rd year
Description
cardiovascular outcome
Time Frame
18 months and 3 year
Title
The number of patients who have new cardiovascular events
Description
cardiovascular events include death from cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention or revascularization for peripheral atherosclerotic arterial disease, and amputation because of ischemia
Time Frame
6 years
Title
changes of UACR
Description
evaluated at 6, 12, 18, 24, 36, 48, 60, 72 months
Time Frame
6 years
Title
changes of eGFR
Description
evaluated at 6, 12, 18, 24, 36, 48, 60, 72 months
Time Frame
6 years
Title
Death from any cause
Description
All-cause mortality
Time Frame
6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qifu Li, PhD
Organizational Affiliation
First Affiliated Hospital of Chongqing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400016
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
23265346
Citation
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Results Reference
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PubMed Identifier
17350370
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.
Results Reference
background
PubMed Identifier
21537349
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.
Results Reference
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PubMed Identifier
17630038
Citation
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Results Reference
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PubMed Identifier
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Results Reference
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PubMed Identifier
18539916
Citation
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Citation
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Low-dose Colchicine in Patients With Type 2 Diabetes Mellitus and Microalbuminuria

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