Minocycline for Aneurysmal Subarachnoid Hemorrhage (MASH)

NCT04876638 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: M.A.S.H.
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Previous work has demonstrated patients presenting with ruptured aneurysms that develop radiographic and clinical vasospasm have a higher permeability of the blood brain membrane. Matrix metalloproteinase 9 (MMP9) has been studied and recently implicated in both the pathogenesis of the blood brain barrier breakdown and vasogenic edema of ischemia strokes, and is suggested to be an accurate biomarker to predict the onset of cerebral vasospasm after subarachnoid hemorrhage. The therapeutic benefit of minocycline, an MMP9 inhibitor, has been investigated in ischemic stroke population, however its role in the treatment of cerebral vasospasm from ruptured aneurysms remains unknown. Our project has two main goals: to further confirm MMP9 has a reliable biomarker for the onset of cerebral vasospasm, and secondarily to investigate any possible therapeutic benefit that minocycline has in the vasospasm population. Vasospasm continues to be one of the major contributors of morbidity and mortality in the ruptured aneurysm population, and close monitoring of the neurologic exam during the 'vasospasm window' usually requires two weeks in the intensive care unit in most academic settings. As such, if we are better able to predict which patients are at risk of developing vasospasm based on MMP9 levels, we will be better able to anticipate the need for intervention and therefore mitigate the risk of vasospasm induced ischemic strokes, ultimately resulting in better outcomes in the ruptured aneurysm population. Further, if we are able to identify minocycline as a therapeutic agent to deter, or lessen the severity of vasospasm, we can possibly improve neurologic outcomes, decrease hospital stays, ultimately providing an improved and more cost-effective treatment strategy to our patients.

Conditions

Aneurysm, Ruptured; Vasospasm, Intracranial; Delayed Cerebral Ischemia; Blood Brain Barrier Defect

Outcome Measures

Primary Outcomes (1)

• Blood brain barrier permeability

  Measured by MRI permeability on post bleed day 5

Secondary Outcomes (2)

• Onset of cerebral vasospasm

  During 2 week vasospasm window following aneurysm rupture

• Serum MMP9 levels

  Measured baseline at time of enrollment and every other day until 14 days

Interventions

Minocyclin DRUG

10mg/kg minocycline up to 700mg for 4 days following aneurysmal subarachnoid hemorrhage

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18 to 85 years, ruptured cerebral aneurysm, enrolled within 24 hours of rupture

You may not qualify if:

• allergy to tetracycline, pregnancy, liver failure, kidney failure

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California Department of Neurosurgery

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• Strickland BA, Barisano G, Abedi A, Shiroishi MS, Cen S, Emanuel B, Bulic S, Kim-Tenser M, Nguyen P, Giannotta SL, Mack W, Russin J. Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial. J Neurosurg. 2021 Oct 29;136(5):1251-1259. doi: 10.3171/2021.6.JNS211270. Print 2022 May 1.

  PMID: 35349976 DERIVED

MeSH Terms

Conditions

Aneurysm, Ruptured; Vasospasm, Intracranial

Interventions

Minocycline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 6, 2021
• Study Start: July 1, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: February 10, 2023

Record last verified: 2023-02

Locations

US (1)