Minocycline and Proteinuria in Diabetic Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01779089
Recruitment Status : Unknown
Verified May 2015 by Los Angeles Biomedical Research Institute.
Recruitment status was:  Active, not recruiting
First Posted : January 30, 2013
Last Update Posted : May 21, 2015
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute

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.

Condition or disease Intervention/treatment Phase
Diabetic Nephropathy Drug: Minocycline 100 mg po bid for 6 months Drug: placebo Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Safety and Efficacy of Minocycline as an Anti-Proteinuric in Diabetic Nephropathy
Study Start Date : February 2009
Estimated Primary Completion Date : March 2016
Estimated Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Minocycline
Minocycline 100 mg po bid for 6 months
Drug: Minocycline 100 mg po bid for 6 months
Minocycline 100 mg po bid or placebo for 6 months

Placebo Comparator: Placebo
Placebo one tablet po bid
Drug: placebo

Primary Outcome Measures :
  1. 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 Measures :
  1. Change in average MACR in 24 hour urine, daytime and overnight collections (baseline vs 6 mos) [ Time Frame: 6 months ]
  2. Change in average 24 hour urine protein/creatinine in daytime vs overnight collections, baseline vs 6 mos [ Time Frame: 6 mos ]
  3. Change in urine and blood biomarkers in minocycline vs placebo treated patients at baseline vs 6 mos [ Time Frame: 6 mos ]

Other Outcome Measures:
  1. Safety [ Time Frame: 6 mos ]
    Track the development of positive ANA and ANCA in placebo and minocycline-treated patients

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01779089

United States, California
Los Angeles Biomedical Reaearch Institute at Harbor-UCLA Medical Center
Torrance, California, United States, 90509
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Principal Investigator: Sharon G Adler, MD Los Angeles Biomedical Research Institute

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Los Angeles Biomedical Research Institute Identifier: NCT01779089     History of Changes
Other Study ID Numbers: 013400
First Posted: January 30, 2013    Key Record Dates
Last Update Posted: May 21, 2015
Last Verified: May 2015

Keywords provided by Los Angeles Biomedical Research Institute:
diabetic nephropathy
diabetic kidney disease

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Urination Disorders
Urological Manifestations
Signs and Symptoms
Anti-Bacterial Agents
Anti-Infective Agents