Use of Minocycline in Intracerebral Hemorrhage

• Sponsor: University of Tennessee Health Science Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03040128
• Collaborator: University of Southern California (Other)
• Enrollment: 20
• Arms: 2
• Actual Duration (Months): 41.1

Study Details

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
• 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: Jun 27, 2013
• Actual Primary Completion Date: Nov 30, 2016
• Actual Study Completion Date: Nov 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 [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 [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 [day 90]

   modified Rankin score (points ranging from 0 to 6)

3. Barthel Index [day 90]

   Barthel Index score (points ranging from 0 to 100)

4. National Institutes of Health Stroke Scale Score [day 90]

   National Institutes of Health Stroke Scale Score (points ranging from 0 to 42)

5. Glasgow Coma Score [day 90]

   Glasgow Coma Score (points ranging from 3 to 15)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

No locations specified.

Sponsors and Collaborators

• University of Tennessee Health Science Center
• University of Southern California

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jason Chang, Principal Investigator, University of Tennessee Health Science Center
• ClinicalTrials.gov Identifier: NCT03040128
• Other Study ID Numbers: MITCH
• First Posted: Feb 2, 2017
• Last Update Posted: Feb 2, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Minocycline

Study Results

No Results Posted as of Feb 2, 2017