Clinical trial NCT03040128: Use of Minocycline in Intracerebral Hemorrhage
Official title: Minocycline and Matrix Metalloproteinase Inhibition in Acute Intracerebral Hemorrhage: A Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Intracerebral Hemorrhage
Lead sponsor: University of Tennessee
Sponsor class: OTHER
Collaborators: name: University of Southern California
First posted: 2017-02-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients with Treatment-related Adverse Effects
timeFrame: day 90
Secondary outcomes:
measure: Volume (ml) of Perihematomal Edema
timeFrame: Change from baseline perihematomal edema volume to chronic (day 5-11) perihematomal edema volume
measure: modified Rankin score
timeFrame: day 90
measure: Barthel Index
timeFrame: day 90
measure: National Institutes of Health Stroke Scale Score
timeFrame: day 90
measure: Glasgow Coma Score
timeFrame: day 90
Other outcomes:
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