Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial

Summary

Background: Stroke is a leading cause of death and chronic serious disability worldwide.

Minocycline, a semisynthetic tetracycline, has consistently been shown in recent years to be neuroprotective in animal models of brain ischemia. Furthermore, a small, open label study done in humans with acute ischemic stroke published late last year showed that minocycline, when administered for 5 days, within 6 to 24 hours after stroke onset was highly effective in improving functional outcome even as early as 7 days after stroke onset. However, further well-conducted, randomized controlled translational studies using minocycline are currently lacking.

Objective: To determine if minocycline, administered within 3 to 48 hours after acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome at 90 days post stroke.

Methods: The investigators plan to do a multi-centre randomized, double-blind, placebo controlled trial in which ischemic stroke patients will be randomized to treatment with either oral minocycline or placebo within 3 to 48 hours of symptom onset. The primary efficacy endpoint will be the modified Rankin scale (mRS) score for all randomized subjects at 90 days.

Secondary endpoints will include improvement of the NIH Stroke Scale (NIHSS) score from baseline and Barthel index at 90 days.

NeuMAST will test the following hypotheses:

Primary Hypothesis: Minocycline, compared with placebo, when administered between 3 to 48 hours after the onset of acute ischemic stroke improves recovery and functional outcome as assessed by mRS scores on day 90 post-stroke.

Secondary Hypotheses:

1. Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves recovery and functional outcome as assessed by improvement of NIHSS score on day 90 post-stroke.
2. Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves functional outcome as assessed by the Barthel Index (BI) score on day 90 post-stroke.
3. Minocycline, compared with placebo reduces 90 day risk of recurrent stroke, MI or death when administered between 3 to 48 hours after acute ischemic stroke onset.

A positive result will have a significant impact in the management of acute ischemic stroke and pave the way for future studies aimed at finding the optimal dose and formulation of minocycline for treating acute ischemic stroke.

Conditions

• Acute Stroke

Interventions

DRUG

Minocycline (Borymycin)

oral dose, 200 mg once a day for 5 days

DRUG

Matched placebo

matched placebo (cornstarch) once a day for 5 days

Sponsors & Collaborators

• National Neuroscience Institute

  collaborator OTHER

• Changi General Hospital

  collaborator OTHER

• Singhealth Foundation

  lead OTHER_GOV

Principal Investigators

• Rajinder Singh, Doctor · National Neuroscience Institute - Tan Tock Seng campus and Changi hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-07-31

Primary Completion

2012-07-31

Completion

2012-11-30

Countries

• Singapore

Study Locations