Clinical trial NCT02495545: Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury
Official title: A Multi-Center, Randomized, Controlled, Trial of Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injury
Keywords: spinal cord injury (SCI)
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
Collaborators: name: University of Miami
First posted: 2015-07-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this Phase IIB randomized controlled trial is to evaluate the safety and efficacy of CSFD and to provide a preliminary clinical efficacy evaluation of the combination of CSFD and elevation of mean arterial pressure (MAP) in patients with acute spinal cord injury (SCI). The objectives of the trial are to evaluate (i) efficacy of reducing intrathecal pressure (ITP) by CSFD in patients with acute SCI; (ii) preliminary efficacy of combination of CSFD and elevation of MAP compared to elevation of MAP alone in improving neurologic motor outcomes in patients with acute SCI; and, (iii) safety of intensive CSFD in acute SCI patients.

Detailed description: Acute spinal cord injury (SCI) affects 10,000-14,000 persons per year in the United States (Burke, Linden et al. 2001). There are 150,000-300,000 persons living with significant disabilities from SCI at any given time (Bernhard, Gries et al. 2005). The average age of incident cases of SCI is 47 years and about 78% of the cases are males (DeVivo and Chen 2011). Estimates of the lifetime costs to care for someone with a SCI range from $325,000 to $1.35 million and the yearly cost to society reaches $8 billion (Sekhon and Fehlings 2001). With better long term care technologies, these costs are expected to continue to rise. Although there have been significant advances in accessibility for people with disabilities, the goal of medical science is to overcome the physiological barriers imposed by the injury itself and allow these individuals to regain their pre-injury level of neurological function (Rowland, Hawryluk et al. 2008). The injury to the spinal cord occurs in two phases. The first phase is the primary physical damage due to the impact energy of the compressive nature of the injury. The damage can be very complex with shearing of the axons, destruction of the cell bodies and disruption of the microvasculature at the site of injury. The secondary phase of the injury begins soon after the primary injury has occurred and can be influenced by many factors such as hypoxia, hypotension, and the extent of the primary injury. Spinal cord ischemia post-injury causes a significant increase in cell death and more significant neurological disability. Limiting tissue hypoperfusion post-injury can decrease the amount of cell death and axonal damage. Lumbar cerebrospinal fluid drainage (CSFD) together with increased mean arterial blood pressure (MAP) in the immediate post-injury period can reduce spinal cord tissue hypoperfusion. By reducing spinal cord hypoperfusion through elevation of MAP, less cell death and axonal damage will occur, leading to an improvement in neurological function. The feasibility of CSFD as a means for reducing the intrathecal pressure (ITP) in patients with acute SCI has been demonstrated in a small randomized controlled trial by Kwon et al (Kwon, Curt et al. 2009). The limitations were a small sample size, broad inclusion criteria, lack of statistical power calculation and restricted drainage regimen (maximum 10 mL per hour).

Eligibility criteria: Inclusion Criteria:

* Aged 18-75 years inclusive;
* Diagnosis of acute SCI;
* Injury is less than 24 hours old;
* ISNCSCI Impairment Scale Grade "A," "B" or "C" based upon first ISNCSCI evaluation after arrival to the hospital;
* Neurological level of injury between C4-C8 based upon first ISNCSCI evaluation after arrival to the hospital;
* Women of childbearing potential must have a negative serum β-hCG pregnancy test or a negative urine pregnancy test;
* Patient is willing to participate in the study;
* Informed consent document signed by patient or witnessed informed consent document;
* No contraindications for study treatment(s);
* Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (includes patients who are on a ventilator).

Exclusion Criteria:

* Injury arising from penetrating mechanism;
* Significant concomitant head injury defined by a Glasgow Coma Scale (GCS) score \< 14 with a clinically significant abnormality on a head CT (head CT required only for patients suspected to have a brain injury at the discretion of the investigator);
* Pre-existing neurologic or mental disorder which would preclude accurate evaluation and follow-up (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric disorder with- hallucinations and/or delusions or schizophrenia);
* Prior history of SCI;
* Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation, in the opinion of the investigator;
* Is a prisoner;
* Participation in another clinical trial within the past 30 days;
* Acquired immune deficiency syndrome (AIDS) or AIDS-related complex;
* Active malignancy or history of invasive malignancy within the last five years, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitely treated. Patients with carcinoma in situ of the uterine cervix treated definitely more than 1 year prior to enrollment may enter the study.

Primary outcomes:
measure: Change in ITP
timeFrame: 120 hours
measure: Change in International Standards for Classification of Spinal Cord Injury Motor Score (ISNCSCI, formerly ASIA)
timeFrame: 180 days
Secondary outcomes:
measure: ISNCSCI Grade
timeFrame: Change in ISNCSCI grade between 180 days and baseline
measure: ISNCSCI Sensory Scores
timeFrame: Change in ISNCSCI Sensory Scores (Light Touch and Pin Prick) between 180 days and baseline
measure: ISNCSCI Upper Extremity Motor Score
timeFrame: Change in ISNCSCI Upper Extremity Motor Score between 180 days and baseline
measure: ISNCSCI Lower Extremity Motor Score
timeFrame: Change in ISNCSCI Lower Extremity Motor Score between 180 days and baseline
measure: Spinal Cord Independence Measure (SCIM)
timeFrame: Spinal Cord Independence Measure (SCIM) at 180 days
measure: Pain level per patient report
timeFrame: Pain Numeric Rating Scale (NRS) at 180 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama School of Medicine Department of Neurosurgery
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Department of Surgery Division of Neurosurgery
state: Arizona
Study officials:
affiliation: Barrow Neurological Institute, St. Joseph's Hospital and Medical Center
name: Nicholas Theodore, MD
role: PRINCIPAL_INVESTIGATOR
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