Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial

NCT00930020 | Terminated Phase 4 DMC

• 1 other identifier: SHF/CTG016/2008
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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.

Conditions

Acute Stroke

Keywords

ischemic stroke recovery; minocycline; neuroprotection; acute stroke

Outcome Measures

Primary Outcomes (1)

• Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke

  3 months

Secondary Outcomes (1)

• Reduction of 90 day risk of recurrent ischemic stroke, myocardial infarction and death

  3 months

Study Arms (2)

matching placebo pill

PLACEBO COMPARATOR

matching placebo

Drug: Matched placebo

Oral minocycline

ACTIVE COMPARATOR

Minocycline 200mg

Drug: Minocycline (Borymycin)

Interventions

Minocycline (Borymycin) DRUG

oral dose, 200 mg once a day for 5 days

Also known as: Borymycin

Oral minocycline

Matched placebo DRUG

matched placebo (cornstarch) once a day for 5 days

Also known as: Placebo - cornstarch

matching placebo pill

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Singapore citizens or permanent residents
• Age range between 21 to 80 years
• NIHSS equal or more than 5 but less than 22 at time of admission
• Clinical diagnosis of acute ischemic stroke according to WHO criteria
• Onset of stroke between 3 to 48 hours prior to start of treatment
• Must have a working telephone line

You may not qualify if:

• Long term residents of Institutions and Nursing homes
• Patients with significant baseline cognitive dysfunction
• Patients with hemorrhagic stroke
• Pre-stroke MRS more than 1
• Evidence of other disease of the CNS (i.e., brain tumor, CNS infections)
• Known allergic response to tetracycline
• Acute or Chronic renal failure
• Hepatitis or liver disease
• Pre-existing infectious disease requiring antibiotics
• Receipts of IV rTPA
• Participation in another clinical trial in the preceding 3 months
• Unable or unwilling to provide inform consent
• Unwilling to return for frequent clinic visits
• Geographic or social factors making the study participation impractical

Sponsors & Collaborators

• Singhealth Foundation: lead
• National Neuroscience Institute: collaborator
• Changi General Hospital: collaborator

Study Sites (1)

National Neuroscience Institute - Tan Tock Seng hospital

Singapore, 308433, Singapore

Location

Related Publications (1)

• Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.

  PMID: 17909152 BACKGROUND

MeSH Terms

Conditions

Stroke; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Rajinder Singh, Doctor

  National Neuroscience Institute - Tan Tock Seng campus and Changi hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: June 30, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 3, 2013

Record last verified: 2013-05

Locations

SG (1)