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Minocycline and Proteinuria in Diabetic Nephropathy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT01779089
First received: January 28, 2013
Last updated: NA
Last verified: January 2013
History: No changes posted
  Purpose

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 Intervention
Diabetic Nephropathy
Drug: Minocycline 100 mg po bid for 6 months
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Safety and Efficacy of Minocycline as an Anti-Proteinuric in Diabetic Nephropathy

Resource links provided by NLM:


Further study details as provided by Los Angeles Biomedical Research Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in average MACR in 24 hour urine, daytime and overnight collections (baseline vs 6 mos) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in average 24 hour urine protein/creatinine in daytime vs overnight collections, baseline vs 6 mos [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Change in urine and blood biomarkers in minocycline vs placebo treated patients at baseline vs 6 mos [ Time Frame: 6 mos ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Safety [ Time Frame: 6 mos ] [ Designated as safety issue: Yes ]
    Track the development of positive ANA and ANCA in placebo and minocycline-treated patients


Enrollment: 30
Study Start Date: February 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01779089

Locations
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
Investigators
Principal Investigator: Sharon G Adler, MD Los Angeles Biomedical Research Institute
  More Information

No publications provided

Responsible Party: Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT01779089     History of Changes
Other Study ID Numbers: 013400
Study First Received: January 28, 2013
Last Updated: January 28, 2013
Health Authority: Los Angeles Biomedical Research Committee at Harbor-UCLA Medical Center, USA:

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

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Urologic Diseases
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014