Back to resultsThe Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization
Primary Purpose
Stroke
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Administration of minocycline
Sponsored by
About this trial
This is an interventional treatment trial for Stroke focused on measuring Minocycline, Neuroprotection, Stroke
Eligibility Criteria
Inclusion Criteria:
- Patients with a clinical indication for carotid revascularization (CRV) as decided by the treating physicians (the clinical indications for CRV as well as the choice of the type of CRV, either CEA or CAS, will be entirely up to the treating physicians)
- Patients who can perform the neurocognitive tests in English
- Women of childbearing age who are non-lactating and have a negative pregnancy test
- Patients in the age range of 18 years - 90 years
- Patients able to undergo MRI imaging.
- Patients that are dependable and able to return for follow-up studies and exams.
- Patients that will be in the hospital (inpatients) the day prior to the procedure for clinical purposes (for evaluation of side effects from the first dose and for overnight infusion of minocycline before the procedure)
Exclusion Criteria:
- Known hypersensitivity to tetracyclines
- Significant neurological deficit including but not limited to dense aphasia, hemi- or mono-paresis (motor strength equal or less than 3/5) or neglect.
- Baseline abnormalities on the MRI of the brain which would preclude the detection of new DWI or FLAIR changes. (e.g large areas of acute stroke, large areas of previous encephalomalacia, existing hardware such as aneurysm clips or coil masses etc.)
- Patients who are pregnant, breast-feeding, or lactating.
- Patients with a contraindication to undergo MRI, including those with pacemakers, metal implants and metal fragments within their bodies.
- Patients with abnormal liver function tests at baseline defined as a 2-fold elevation in alanine-aminotransferase.
- Patients with significantly affected renal function at baseline (Creatinine equal or above 2mg/dL).
- Patients on high dose isotretinoin, vitamin A, or methotrexate
- Patients undergoing emergency carotid revascularization procedures.
- Any clinically important known medical, surgical, psychiatric or psychological disease, which would preclude completion of the protocol (such as advanced cardiac, renal or pulmonary disease).We will screen for physical and mental capacity to undergo study procedures and will obtain proxy consent for subjects who appear decisionally impaired. The screening process will be performed by the physician co-investigator obtaining the informed consent.
- Patients with a Mini-Mental Status Exam score (MMSE) of less than 21 (as determined by one of the co-investigators). Patients with MMSE score of 21 will be included.
- Patients undergoing carotid revascularization in less than 36 hours from identification, or patients who are undecided about participation less than 36 hours prior to the procedure will not be eligible for the study.
- Patients with any other factor that would make follow-up studies difficult (e.g patient is from another country, or patient is a prisoner)
Sites / Locations
- Presbyterian Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Administration of minocycline
Arm Description
All patients in the study will receive minocycline periprocedurally with the following schedule: Day prior to procedure: 800mg p.o., 700mg p.o. Day of procedure: 600mg i.v., 500mg p.o. Day after procedure: 400mg p.o., 400mg p.o.
Outcomes
Primary Outcome Measures
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
The primary aim of this phase I study is to establish the safety and tolerability of this drug in patient population undergoing carotid revascularization procedures by monitoring complete blood counts, liver enzymes, renal function tests, and clinical side effects
During the above time frame (one day prior to procedure until 1 day after the procedure) the number of patients that develop any side effects requiring discontinuation of the drug will be noted.
Side effects that will lead to discontinuation of the drug are the following:
The patient reports a clinical side effect as intolerable (nausea /vomiting, dysphagia, rash, vertigo or other side effects attributable to the administration of minocycline)
Change in liver function tests ( 2 times elevation of alanine-aminotransferase above the normal range)
Change in renal function tests (creatinine more than 1.5 points from baseline)
Secondary Outcome Measures
Progression of procedural stroke on MRI imaging
Secondary Aim 1:To examine the effect of perioperative treatment with minocycline on the number and overall volume of new neurologic ischemic lesions detected by Diffusion Weighted Imaging (DWI) within 24 hours following carotid revascularization, and on the conversion of these acute lesions to persistent changes on Magnetic Resonance Imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequences. The findings in the study's cohort of patients will be compared to historical controls
Neuropsychological test performance
To examine the effect of perioperative minocycline on neuropsychological test performance. The findings in the study's cohort of patients will be compared to historical controls
Myocardial Infarction
To examine the effect of preoperative minocycline on the incidence of myocardial infarction during carotid revascularization procedures. The findings in the study's cohort of patients will be compared to historical controls. Myocardial infarction will be investigated based on clinical grounds, electrocardiographic findings, and elevation of troponins.
Markers of neuronal injury
To examine the effect of perioperative minocycline on markers of neuronal injury (Neuron Specific Enolase and S100b) as well as inflammation C- reactive protein). The findings in the study's cohort of patients will be compared to historical controls
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02178813
Brief Title
The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization
Official Title
The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization. A Phase I Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Why Stopped
Study stopped prematurely because of multiple logistic difficulties
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pittsburgh
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of high-dose minocycline in the patient population undergoing carotid revascularization procedures, namely carotid endarterectomy (CEA) and carotid artery stenting (CAS). Establishment of safety will facilitate proceeding to a phase II trial.
During this trial, patients undergoing carotid revascularization procedures will receive high doses of minocycline with the following schedule (based on previous trials):
Day prior to procedure: 800mg orally (p.o), 700mg p.o.
Day of procedure: 600mg intravenously( i.v.), 500mg p.o.
Day after procedure: 400mg p.o., 400mg p.o.
The levels of the drug in the plasma, standard blood tests (complete blood count, creatinine, liver function tests) as well as markers of neuronal injury (Neuron specific enolase, protein- S100b) and inflammation (C-reactive protein) will also be monitored. The patients will be monitored closely for the development of side effects from minocycline.
MRI imaging will be used to follow the development of small strokes as a result of the revascularization procedures and their resolution. The patients of this study, all receiving peri-operative minocycline, will be compared with historical controls with regards to development of small strokes and persistent of these strokes on subsequent MRI imaging.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Minocycline, Neuroprotection, Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Administration of minocycline
Arm Type
Experimental
Arm Description
All patients in the study will receive minocycline periprocedurally with the following schedule:
Day prior to procedure: 800mg p.o., 700mg p.o.
Day of procedure: 600mg i.v., 500mg p.o.
Day after procedure: 400mg p.o., 400mg p.o.
Intervention Type
Drug
Intervention Name(s)
Administration of minocycline
Other Intervention Name(s)
Minocycline (generic name)
Intervention Description
Administration of minocycline with the following schedule:
Day prior to procedure: 800mg p.o., 700mg p.o.
Day of procedure: 600mg i.v., 500mg p.o.
Day after procedure: 400mg p.o., 400mg p.o.
Primary Outcome Measure Information:
Title
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
Description
The primary aim of this phase I study is to establish the safety and tolerability of this drug in patient population undergoing carotid revascularization procedures by monitoring complete blood counts, liver enzymes, renal function tests, and clinical side effects
During the above time frame (one day prior to procedure until 1 day after the procedure) the number of patients that develop any side effects requiring discontinuation of the drug will be noted.
Side effects that will lead to discontinuation of the drug are the following:
The patient reports a clinical side effect as intolerable (nausea /vomiting, dysphagia, rash, vertigo or other side effects attributable to the administration of minocycline)
Change in liver function tests ( 2 times elevation of alanine-aminotransferase above the normal range)
Change in renal function tests (creatinine more than 1.5 points from baseline)
Time Frame
One day prior to procedure to 1 days after procedure
Secondary Outcome Measure Information:
Title
Progression of procedural stroke on MRI imaging
Description
Secondary Aim 1:To examine the effect of perioperative treatment with minocycline on the number and overall volume of new neurologic ischemic lesions detected by Diffusion Weighted Imaging (DWI) within 24 hours following carotid revascularization, and on the conversion of these acute lesions to persistent changes on Magnetic Resonance Imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequences. The findings in the study's cohort of patients will be compared to historical controls
Time Frame
10 days before procedure, 1 day after procedure, 1 month after procedure
Title
Neuropsychological test performance
Description
To examine the effect of perioperative minocycline on neuropsychological test performance. The findings in the study's cohort of patients will be compared to historical controls
Time Frame
10 days prior to procedure, 1 day after procedure, 1 month after procedure
Title
Myocardial Infarction
Description
To examine the effect of preoperative minocycline on the incidence of myocardial infarction during carotid revascularization procedures. The findings in the study's cohort of patients will be compared to historical controls. Myocardial infarction will be investigated based on clinical grounds, electrocardiographic findings, and elevation of troponins.
Time Frame
Days 1, 2(procedure day), 3
Title
Markers of neuronal injury
Description
To examine the effect of perioperative minocycline on markers of neuronal injury (Neuron Specific Enolase and S100b) as well as inflammation C- reactive protein). The findings in the study's cohort of patients will be compared to historical controls
Time Frame
1 day prior to procedure, 1 day after the procedure, 1 month after the procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with a clinical indication for carotid revascularization (CRV) as decided by the treating physicians (the clinical indications for CRV as well as the choice of the type of CRV, either CEA or CAS, will be entirely up to the treating physicians)
Patients who can perform the neurocognitive tests in English
Women of childbearing age who are non-lactating and have a negative pregnancy test
Patients in the age range of 18 years - 90 years
Patients able to undergo MRI imaging.
Patients that are dependable and able to return for follow-up studies and exams.
Patients that will be in the hospital (inpatients) the day prior to the procedure for clinical purposes (for evaluation of side effects from the first dose and for overnight infusion of minocycline before the procedure)
Exclusion Criteria:
Known hypersensitivity to tetracyclines
Significant neurological deficit including but not limited to dense aphasia, hemi- or mono-paresis (motor strength equal or less than 3/5) or neglect.
Baseline abnormalities on the MRI of the brain which would preclude the detection of new DWI or FLAIR changes. (e.g large areas of acute stroke, large areas of previous encephalomalacia, existing hardware such as aneurysm clips or coil masses etc.)
Patients who are pregnant, breast-feeding, or lactating.
Patients with a contraindication to undergo MRI, including those with pacemakers, metal implants and metal fragments within their bodies.
Patients with abnormal liver function tests at baseline defined as a 2-fold elevation in alanine-aminotransferase.
Patients with significantly affected renal function at baseline (Creatinine equal or above 2mg/dL).
Patients on high dose isotretinoin, vitamin A, or methotrexate
Patients undergoing emergency carotid revascularization procedures.
Any clinically important known medical, surgical, psychiatric or psychological disease, which would preclude completion of the protocol (such as advanced cardiac, renal or pulmonary disease).We will screen for physical and mental capacity to undergo study procedures and will obtain proxy consent for subjects who appear decisionally impaired. The screening process will be performed by the physician co-investigator obtaining the informed consent.
Patients with a Mini-Mental Status Exam score (MMSE) of less than 21 (as determined by one of the co-investigators). Patients with MMSE score of 21 will be included.
Patients undergoing carotid revascularization in less than 36 hours from identification, or patients who are undecided about participation less than 36 hours prior to the procedure will not be eligible for the study.
Patients with any other factor that would make follow-up studies difficult (e.g patient is from another country, or patient is a prisoner)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Georgios A Zenonos, MD
Organizational Affiliation
University of Pittsburgh Resident in Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Presbyterian Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15206
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22505632
Citation
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.
Results Reference
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Learn more about this trial
The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization
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