NCT01058395

Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI)

Phase I Study of Minocycline in a Dose Escalation Study as a Safe, Efficacious Therapeutic Intervention for Moderate and Severe TBI in Humans

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Wayne State University · Academic / Other
• Sex: Male
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is: 1. To assess the safety and feasibility of minocycline administration after TBI in a dose escalation study at two different doses over 7 days. 2. To assess the pharmacokinetic characteristics of two different dosing regimens of minocycline in TBI patients, the effect on biochemical markers of neuroprotective mechanisms, and effect on neurobehavioral and functional outcome. 3. To begin initial assessment of the efficacy of minocycline as a therapeutic agent for severe human TBI.

Detailed description

The purpose of this preliminary study is to test the hypothesis that administration of minocycline to humans with moderate and severe TBI is both safe and feasible in the acute post-injury setting, and to characterize its disposition and effects on biomarkers of traumatic CNS injury in a Phase IIa trial. The data collected will serve as the basis for a larger Phase IIb clinical trial in a randomized placebo-controlled parallel group design, to investigate further its potential safety and efficacy as a therapeutic agent for severe human TBI. Tetracycline derivatives, including doxycycline and minocycline, have been shown to be neuroprotective when given after traumatic brain injury (TBI) and ischemia in rodents. In particular, reduced lesion volume and improved neurological outcome have been demonstrated following minocycline treatment of TBI. The proposed mechanism for these observations is multifactorial, and includes inhibition of microglial activation, caspase-mediated apoptosis, and the excitotoxic N-methyl-D-aspartic acid (NMDA) pathway. Because comparable inflammatory, excitotoxic and apoptotic pathways have also been implicated in human TBI, we hypothesize that administration of minocycline will confer neuroprotection after moderate to severe TBI in that milieu as well, with the potential for significant clinical benefit. Minocycline is highly lipophilic, and thus penetrates the human central nervous system (CNS). In addition, it has been shown to be safe when used in non-traumatic human neurological disorders.

Conditions

• Traumatic Brain Injury

Interventions

Type	Name	Description
DRUG	Minocycline	Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.

Timeline

• Start date: 2010-02-01
• Primary completion: 2015-09-01
• Completion: 2016-01-01
• First posted: 2010-01-28
• Last updated: 2018-09-17
• Results posted: 2018-09-17

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study