Back to resultsMinocycline and Proteinuria in Diabetic Nephropathy
Primary Purpose
Diabetic Nephropathy
Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Minocycline 100 mg po bid for 6 months
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Nephropathy focused on measuring diabetic nephropathy, diabetic kidney disease, minocycline, proteinuria, albuminuria
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of diabetes and diabetic nephropathy as described in the Family Investigation of Nephropathy and Diabetes Protocol
- Baseline creatinine clearance > 30 mL/min/1.73 m2 (at first screening visit)
- Proteinuria ≥ 1.0 g/day (at first screening visit)
- Age ≥30 years
- BP at baseline <150/95 mm Hg (measured sitting after 10 min rest at first screening visit)
- Adequate hepatic function defined as total bilirubin < 1.5 x the upper limit of the normal range (ULN), AST (SGOT) and ALT (SGPT) < 2.5 x ULN.
- Patients taking ACEi, angiotensin receptor blockers (ARBs), aliskerin, spironolactone and/or diltiazem may be entered, but dosing may not change during the period of study or within 1 month prior to the first of the baseline proteinuria measurements.
Exclusion Criteria:• NSAID (including COX-2 inhibitors) use > 3 tabs/week habitually
- Diagnosis of neurodegenerative diseases (Parkinson's disease, Huntington's disease, multiple sclerosis, Alzheimer's disease, etc).
- Any unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
- History of liver disease (screening AST > 3 times the upper limit of normal)
- History of hematologic disease (screening white blood cell count less than 3,800/mm3)
- History of systemic vasculitis or systemic lupus erythematosus
- Treatment with procainamide or hydralazine
- History of vestibular disease (excluding benign position vertigo)
- Pregnancy or lactation
- Allergy to tetracycline antibiotics
- Use of minocycline within thirty days of baseline visit
- Use of anti-epileptic medications other than gabapentin
- Use of lithium, digoxin, warfarin, other anticoagulants, and theophylline
- Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures
- History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols
- Use of any investigational drug within 30 days prior to the baseline visit
- Women with the potential to become pregnant who are not willing to practice double-barrier birth control
Sites / Locations
- Los Angeles Biomedical Reaearch Institute at Harbor-UCLA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Minocycline
Placebo
Arm Description
Minocycline 100 mg po bid for 6 months
Placebo one tablet po bid
Outcomes
Primary Outcome Measures
Change in 24 hour urine protein/creatinine ratio (average of 2 values) baseline compared to 6-months in placebo vs minocycline
Secondary Outcome Measures
Change in average MACR in 24 hour urine, daytime and overnight collections (baseline vs 6 mos)
Change in average 24 hour urine protein/creatinine in daytime vs overnight collections, baseline vs 6 mos
Change in urine and blood biomarkers in minocycline vs placebo treated patients at baseline vs 6 mos
Full Information
NCT ID
NCT01779089
First Posted
January 28, 2013
Last Updated
May 20, 2015
Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01779089
Brief Title
Minocycline and Proteinuria in Diabetic Nephropathy
Official Title
The Safety and Efficacy of Minocycline as an Anti-Proteinuric in Diabetic Nephropathy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
February 2009 (undefined)
Primary Completion Date
March 2016 (Anticipated)
Study Completion Date
March 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Diabetic kidney disease increases the risk of illness and death from heart disease in patients with Type 2 diabetes. Some blood pressure medications called ACE inhibitors and ARBs slow progression of kidney disease, but the dose that can be used is often limited by side effects that are experienced by patients. The most limiting side effects of the current treatments are lowering of the kidney function or blood pressure, and a rise in blood potassium levels. A safe and inexpensive medication that doesn't lower kidney function or blood pressure or raise serum potassium would be useful.
Minocycline is a tetracycline antibiotic with recently appreciated protective properties. In a published journal article by Dr. Isermann, minocycline prevented the death of specialized kidney cells in mice. The kidneys of these mice did not develop diabetic kidney disease when seen under the microscope and the mice experienced only a little bit of protein loss in the urine. In a different published paper, the authors showed that minocycline also decreased kidney injury in a model of non-diabetic kidney disease. A related tetracycline antibiotic was shown to lower urine protein in diabetic patients. These data support a rationale for testing to see if minocycline is safe and helpful in patients with diabetic kidney disease. In this study, all patients will stay on their usual medications for the treatment of diabetic kidney disease. Patients will be given either minocycline (100 mg by mouth twice a day for 24 weeks) or placebo (an inactive capsule taken twice a day for 24 weeks). Minocycline or placebo will be assigned by a process called "randomization", which is like a coin toss. Neither the patient nor the study team will know if the patient is taking placebo or minocycline until the end of the study. The study will assess minocycline safety and test to see if minocycline is helpful or not helpful for the treatment of diabetic kidney disease.
This study was funded by the American Diabetes Association and is not supported by any pharmaceutical company.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
Keywords
diabetic nephropathy, diabetic kidney disease, minocycline, proteinuria, albuminuria
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Minocycline
Arm Type
Experimental
Arm Description
Minocycline 100 mg po bid for 6 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo one tablet po bid
Intervention Type
Drug
Intervention Name(s)
Minocycline 100 mg po bid for 6 months
Intervention Description
Minocycline 100 mg po bid or placebo for 6 months
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
Change in 24 hour urine protein/creatinine ratio (average of 2 values) baseline compared to 6-months in placebo vs minocycline
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in average MACR in 24 hour urine, daytime and overnight collections (baseline vs 6 mos)
Time Frame
6 months
Title
Change in average 24 hour urine protein/creatinine in daytime vs overnight collections, baseline vs 6 mos
Time Frame
6 mos
Title
Change in urine and blood biomarkers in minocycline vs placebo treated patients at baseline vs 6 mos
Time Frame
6 mos
Other Pre-specified Outcome Measures:
Title
Safety
Description
Track the development of positive ANA and ANCA in placebo and minocycline-treated patients
Time Frame
6 mos
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of diabetes and diabetic nephropathy as described in the Family Investigation of Nephropathy and Diabetes Protocol
Baseline creatinine clearance > 30 mL/min/1.73 m2 (at first screening visit)
Proteinuria ≥ 1.0 g/day (at first screening visit)
Age ≥30 years
BP at baseline <150/95 mm Hg (measured sitting after 10 min rest at first screening visit)
Adequate hepatic function defined as total bilirubin < 1.5 x the upper limit of the normal range (ULN), AST (SGOT) and ALT (SGPT) < 2.5 x ULN.
Patients taking ACEi, angiotensin receptor blockers (ARBs), aliskerin, spironolactone and/or diltiazem may be entered, but dosing may not change during the period of study or within 1 month prior to the first of the baseline proteinuria measurements.
Exclusion Criteria:• NSAID (including COX-2 inhibitors) use > 3 tabs/week habitually
Diagnosis of neurodegenerative diseases (Parkinson's disease, Huntington's disease, multiple sclerosis, Alzheimer's disease, etc).
Any unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
History of liver disease (screening AST > 3 times the upper limit of normal)
History of hematologic disease (screening white blood cell count less than 3,800/mm3)
History of systemic vasculitis or systemic lupus erythematosus
Treatment with procainamide or hydralazine
History of vestibular disease (excluding benign position vertigo)
Pregnancy or lactation
Allergy to tetracycline antibiotics
Use of minocycline within thirty days of baseline visit
Use of anti-epileptic medications other than gabapentin
Use of lithium, digoxin, warfarin, other anticoagulants, and theophylline
Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures
History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols
Use of any investigational drug within 30 days prior to the baseline visit
Women with the potential to become pregnant who are not willing to practice double-barrier birth control
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharon G Adler, MD
Organizational Affiliation
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Los Angeles Biomedical Reaearch Institute at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27019421
Citation
Shah AP, Shen JI, Wang Y, Tong L, Pak Y, Andalibi A, LaPage JA, Adler SG. Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial. PLoS One. 2016 Mar 28;11(3):e0152357. doi: 10.1371/journal.pone.0152357. eCollection 2016.
Results Reference
derived
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Minocycline and Proteinuria in Diabetic Nephropathy
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