Intra-Arterial Neuroprotective Agents and Cold Saline in Ischemic Stroke Intervention

NCT05032781 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-1198
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Ischemic stroke is the leading cause of long-term disability in the United States. Endovascular intervention with mechanical thrombectomy has become the standard of care for acute large vessel occlusion (LVO) stroke since multiple clinical trials demonstrated improved long-term clinical outcomes with treatment. However, despite high rates of successful vessel recanalization and thus reperfusion of ischemic brain tissue in current practice, many patients continue to suffer debilitating strokes and poor long-term functional outcome. Pharmacologic neuroprotection could potentially present a means of addressing this mismatch in radiologic vs. clinical outcomes by protecting and salvaging damaged brain tissue. Intra-arterial delivery of a cocktail of neuroprotective therapy at the time of endovascular reperfusion would provide immediate, targeted therapy directly to the damaged brain territory. Hypothermia, minocycline and magnesium can target multiple facets of the complex ischemic injury cascade, and have each demonstrated neuroprotection in multiple preclinical models. This is a phase I trial that aims to demonstrate safety and feasibility of administering cold saline, minocycline, and magnesium sulfate intra-arterially immediately after thrombectomy in stroke interventions.

Conditions

Stroke, Ischemic

Keywords

Ischemic stroke; Large vessel occlusion; Mechanical thrombectomy; Neuroprotection; cold saline; Minocycline; Magnesium sulfate

Outcome Measures

Primary Outcomes (2)

• Intracranial hemorrhage

  Presence of symptomatic intracranial hemorrhage

  within 24 hours of treatment

• Presence of serious adverse event

  Related to intra-arterial administration of cold saline, minocycline, or magnesium sulfate

  within 72 hours of treatment

Secondary Outcomes (2)

• Infarct volume

  24 hours after procedure

• Functional outcome

  90 days after intervention

Study Arms (1)

Intra-arterial neuroprotective substances

EXPERIMENTAL

Cold saline, minocycline, and magnesium sulfate to be infused intra-arterially immediately after thrombectomy via the internal carotid artery. A dose escalation design will be used, as described above in "Study Description."

Drug: Intra-arterial cold saline, minocycline, and magnesium

Interventions

Intra-arterial cold saline, minocycline, and magnesium DRUG

See study design

Intra-arterial neuroprotective substances

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18-90
• Signed and dated informed consent and IRB form by the patient or legally authorized health care proxy.
• Diagnosis of acute ischemic stroke due to large vessel occlusion based on clinical and radiographic evidence as determined and documented by the Stroke Neurology team at Northshore University Hospital.
• Participants must meet criteria for intra-arterial thrombectomy as determined and documented by the Stroke Neurology and Interventional Neuroradiology attending physicians at Northshore University Hospital.
• Angiography must reveal a thromboembolism which is completely occluding flow within the intracranial portion of the internal carotid artery, the M1 or proximal M2 portions of the middle cerebral artery.

You may not qualify if:

• Patients that do not otherwise meet criteria for endovascular intervention
• Large vessel occlusion of the anterior cerebral artery, posterior circulation, or distal M2 portion of the middle cerebral artery.
• Recanalization of only TICI 0-2A.
• Pregnant or lactating women.
• Therapeutic anticoagulation prior to presentation.
• Known allergic reactions to contrast dye or components of minocycline (tetracycline) or magnesium sulfate.
• Patients with a known prior diagnosis of heart block or prior myocardial infarction (increased risk of adverse reaction to MgSO4).
• Renal insufficiency (creatinine \> 2.5 mg/dL)
• Severe hepatic functional impairment (AST \> 10xULN, bilirubin \> 5xULN)
• Systemic lupus erythematosus
• Idiopathic intracranial hypertension

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

North Shore University Hospital

Manhasset, New York, 11030, United States

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke; cyclopia sequence

Interventions

Minocycline; Magnesium

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Thomas W Link, MD, MS

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas W Link, MD, MS

CONTACT

516-562-4300; tlink@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: See study design

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: September 2, 2021
• Study Start: June 1, 2021
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2025
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)