Use of Minocycline in Intracerebral Hemorrhage

• ClinicalTrials.gov Identifier: NCT03040128
• Recruitment Status: Completed
• First Posted: February 2, 2017
• Last Update Posted: February 2, 2017
• Sponsor: University of Tennessee Health Science Center
• Collaborator: University of Southern California
• Information provided by (Responsible Party): Jason Chang, University of Tennessee Health Science Center

Study Description

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

Condition or disease	Intervention/treatment	Phase
Intracerebral Hemorrhage	Drug: Minocycline; Other: normal saline infusion	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: random number generator (placebo vs. study drug)
• Primary Purpose: Treatment
• Official Title: Minocycline and Matrix Metalloproteinase Inhibition in Acute Intracerebral Hemorrhage: A Pilot Trial
• Actual Study Start Date: June 27, 2013
• Actual Primary Completion Date: November 30, 2016
• Actual Study Completion Date: November 30, 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: placebo; normal saline infusion	Other: normal saline infusion
Experimental: minocycline; intravenous minocycline	Drug: Minocycline; high-dose, intravenous minocycline

Outcome Measures

Primary Outcome Measures :

1. Number of patients with Treatment-related Adverse Effects [ Time Frame: day 90 ]
   Treatment-related adverse effects as noted by package insert: fever, nausea, vomiting, C-diff, hepatic toxicity, dermatitis, anaphylaxis, renal injury)

Secondary Outcome Measures :

1. Volume (ml) of Perihematomal Edema [ Time Frame: Change from baseline perihematomal edema volume to chronic (day 5-11) perihematomal edema volume ]
   Volumetric analysis (ml) computed from computed tomography head
2. modified Rankin score [ Time Frame: day 90 ]
   modified Rankin score (points ranging from 0 to 6)
3. Barthel Index [ Time Frame: day 90 ]
   Barthel Index score (points ranging from 0 to 100)
4. National Institutes of Health Stroke Scale Score [ Time Frame: day 90 ]
   National Institutes of Health Stroke Scale Score (points ranging from 0 to 42)
5. Glasgow Coma Score [ Time Frame: day 90 ]
   Glasgow Coma Score (points ranging from 3 to 15)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Jason Chang, Principal Investigator, University of Tennessee Health Science Center
• ClinicalTrials.gov Identifier: NCT03040128
• Other Study ID Numbers: MITCH
• First Posted: February 2, 2017
• Last Update Posted: February 2, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Minocycline; Anti-Bacterial Agents; Anti-Infective Agents