Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study

Eur J Neurol. 2017 Nov;24(11):1384-1391. doi: 10.1111/ene.13403. Epub 2017 Sep 20.

Abstract

Background and purpose: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial.

Methods: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality.

Results: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5.

Conclusions: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

Keywords: cerebrovascular disorder; edema; inhibition; intracerebral hemorrhage; matrix metalloproteinase; minocycline; neuroprotection; stroke.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase Inhibitors / therapeutic use*
  • Middle Aged
  • Minocycline / therapeutic use*
  • Pilot Projects
  • Treatment Outcome

Substances

  • Matrix Metalloproteinase Inhibitors
  • Minocycline