Use of Minocycline in Intracerebral Hemorrhage

NCT ID: NCT03040128

Last Updated: 2017-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-27
• Study Completion Date: 2016-11-30

Brief Summary

To date, no neuroprotective drugs have demonstrated clinical efficacy in intracerebral hemorrhage (ICH). This study will use intravenous (IV) minocycline in ICH to evaluate for (1) safety/ tolerability and (2) evaluate for clinical efficacy

Detailed Description

Intracerebral hemorrhage (ICH) remains a devastating neurological disorder with high mortality and poor prognosis with unchanged mortality rates (53-59%). Acute treatment options for ICH remain supportive with no available effective drug or surgical therapy. All trials so far have failed to improve clinical outcome in randomized, double-blinded trials. However, one area of interest has been maintaining the integrity of the blood-brain-barrier (BBB) and preventing the growth of vasogenic edema. Matrix metalloproteinases (MMP) are a family of ubiquitous zinc-dependent endopeptidase enzymes whose primary function is the digestion of collagen type IV, laminin, and fibronectin for the purpose of remodeling extracellular basal lamina. Elevated MMP-9 as a pathological process associated with larger hematoma volume, larger perihematomal edema, and poorer clinical outcome in intracerebral hemorrhage is well documented in animal models and patients. One particular MMP-9 inhibitor gaining usage in cerebrovascular disease is minocycline. Normally FDA-approved for bacterial infection and acne vulgaris, minocycline has also been found to be both a safe and effective treatment in ischemic stroke; its potential role as a neuroprotectant in ischemic stroke is currently being tested in a large, randomized, double-blinded trial. Minocycline's beneficial role as a neuroprotectant may also extend to ICH. By inhibiting MMP-9, minocycline may decrease BBB permeability, resulting in less perihematomal edema and decreased mass effect. Although numerous animal ICH models support minocycline's role as an inhibitor of MMP-9 and neuroprotectant, its use has never been studied in humans with ICH.

Conditions

Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

placebo

normal saline infusion

Group Type: PLACEBO_COMPARATOR

normal saline infusion

Intervention Type: OTHER

minocycline

intravenous minocycline

Group Type: EXPERIMENTAL

Minocycline

Intervention Type: DRUG

high-dose, intravenous minocycline

Interventions

Minocycline

high-dose, intravenous minocycline

Intervention Type: DRUG

normal saline infusion

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age 18-80 yo

2. Acute neurological deficit with corresponding ICH noted on head CT

3. Glasgow Coma Scale (GCS) > 8

4. Onset of symptoms within 12 hrs

5. < 30 ml of blood noted on initial CTH (30 ml hematoma volume is a noted independent marker between good and poor clinical outcome)

6. ICH score < 3

7. English/ Spanish speaking

Exclusion Criteria

1. Allergy to tetracycline and tetracycline analogues

2. Pregnancy or suspected pregnancy

3. Hepatic and/or renal insufficiency (LFTs 3x greater than upper limit of normal; creatinine > 2 mg/dL)

4. Thrombocytopenia (plt count < 75,000)

5. History of intolerance to minocycline

6. Baseline modified Rankin score > 1

7. Stuporous or comatose (GCS < 8)

8. Presence of concomitant serious illness that would confound study, including serious psychiatric disease or prior suicide attempts.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Southern California

OTHER

Sponsor Role: collaborator

University of Tennessee

OTHER

Sponsor Role: lead

Responsible Party

Jason Chang

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

MITCH

Identifier Type: -

Identifier Source: org_study_id