Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury

November 25, 2019 updated by: St. Joseph's Hospital and Medical Center, Phoenix

A Multi-Center, Randomized, Controlled, Trial of Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3410
        • University of Alabama School of Medicine Department of Neurosurgery
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute St. Joseph's Hospital and Medical Center
      • Tucson, Arizona, United States, 85724-5070
        • University of Arizona Department of Surgery Division of Neurosurgery

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CSFD with elevation of MAP
Subjects will receive CSFD and elevation of MAP. Treatments will be 120 hours (5 days) from time treatment is initiated (time 0), and within 24 hours of time of injury. Initiation of CSFD will occur after decompression (during surgery) with a target ITP of 10 mmHg. MAP elevation (norepinephrine drip; goal 100-110 mmHg) will start during surgery, simultaneously with CSFD. 10 mL of CSF will be collected daily for routine lab testing. Post-surgery subjects will be transferred to an intensive care unit (ICU) for duration of treatment or longer if clinically indicated. Target MAP will be sustained within 100-110 mmHg for 5 days. Norepinephrine drip will be used to maintain MAP goal. Subjects will receive other treatment per standard of care at the participating investigational sites.
Procedure: CSFD and elevation of MAP
Lumbar drain placement with CSFD with elevation of MAP
Active Comparator: Maintenance of MAP
Subjects will receive elevation of MAP (norepinephrine drip; goal 85-90 mm Hg). Target MAP will be sustained within 85-90 mmHg in the control group for 5 days. Duration of elevation of MAP treatment will be 120 hours (5 days) from time treatment is (time 0). Subjects will receive the same treatment as the subjects in investigational arm except for the initiation of the CSFD and less aggressive MAP elevation. They will have a drain placed the same way as the experimental subjects. While drain is in place, 10 mL of cerebrospinal fluid will be collected daily for laboratory testing. After that, ITP will be monitored but CSFD will not be initiated. Subjects will receive other treatment per standard of care at participating investigational sites.
Procedure: Maintenance of MAP
Lumbar drain placement without CSFD and with maintenance of MAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ITP
Time Frame: 120 hours
ITP will be measured in both groups every hour for the duration of study treatment for a total of 121 measurements consisting of one pre-treatment measurement (time 0 hours) and 120 measurements during the treatment (time 1-120 hours).
120 hours
Change in International Standards for Classification of Spinal Cord Injury Motor Score (ISNCSCI, formerly ASIA)
Time Frame: 180 days
ISNCSCI Motor Score will be obtained at hospital arrival (baseline), 72 hours post-injury, 84 days and 180 days post-treatment. The primary endpoint is difference between the Motor Score at 180 days and baseline.
180 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ISNCSCI Grade
Time Frame: Change in ISNCSCI grade between 180 days and baseline
Change in ISNCSCI grade between 180 days and baseline
ISNCSCI Sensory Scores
Time Frame: Change in ISNCSCI Sensory Scores (Light Touch and Pin Prick) between 180 days and baseline
Change in ISNCSCI Sensory Scores (Light Touch and Pin Prick) between 180 days and baseline
ISNCSCI Upper Extremity Motor Score
Time Frame: Change in ISNCSCI Upper Extremity Motor Score between 180 days and baseline
Change in ISNCSCI Upper Extremity Motor Score between 180 days and baseline
ISNCSCI Lower Extremity Motor Score
Time Frame: Change in ISNCSCI Lower Extremity Motor Score between 180 days and baseline
Change in ISNCSCI Lower Extremity Motor Score between 180 days and baseline
Spinal Cord Independence Measure (SCIM)
Time Frame: Spinal Cord Independence Measure (SCIM) at 180 days
Spinal Cord Independence Measure (SCIM) at 180 days
Pain level per patient report
Time Frame: Pain Numeric Rating Scale (NRS) at 180 days
Using a numeric pain rating scale, subjects will indicate level of pain at time measure occurs
Pain Numeric Rating Scale (NRS) at 180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

University of Miami

Investigators

  • Principal Investigator: Nicholas Theodore, MD, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Actual)

October 25, 2019

Study Completion (Actual)

October 25, 2019

Study Registration Dates

First Submitted

July 8, 2015

First Submitted That Met QC Criteria

July 8, 2015

First Posted (Estimate)

July 13, 2015

Study Record Updates

Last Update Posted (Actual)

November 27, 2019

Last Update Submitted That Met QC Criteria

November 25, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHX 14BN084

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Spinal Cord Injury

Clinical Trials on CSFD and elevation of MAP

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burundi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe