Autologous Incubated Macrophages for Patients With Complete Spinal Cord Injuries

A Phase II Multicenter, Randomized-Controlled Study to Evaluate the Safety and Efficacy of Autologous Incubated Macrophages for the Treatment of Patients With Complete Spinal Cord Injuries

Autologous Incubated Macrophages (ProCord) is being developed as a therapy for acute, complete spinal cord injury (SCI). The therapy is intended to reverse the loss of motor and sensory function.

Following non-CNS tissue injury, macrophages quickly arrive on the scene, where they clean up cell debris, secrete different molecules thus promoting a controlled inflammatory reaction that forms the first phase of the wound healing process. While this process occurs in most tissues, including peripheral nerves, it does not occur in the CNS, where macrophages and other immune cells are relatively rare, and their activities curtailed by a biochemical mechanism known as "immune privilege."

In animal studies, it appears that incubated macrophages circumvent the immune privilege, thus supporting the regrowth of axons through the injury site and enabling the recovery of neurological function. The concept derives from the pioneering research of Prof. Michal Schwartz at the Weizmann Institute of Science.

Study Overview

• Status: Suspended
• Conditions: Spinal Cord Injury
• Intervention / Treatment: Procedure: Autologous Incubated Macrophages (cell therapy)

• Study Type: Interventional
• Enrollment: 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
• United States
  • Colorado
    • Englewood, Colorado, United States, 80110
      • Craig Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ
    • West Orange, New Jersey, United States, 07052
      • Kessler Medical Rehabilitation Research and Education Corporation
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Spinal Cord Injury Model System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Shriners Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Traumatic SCI during last 14 days
• Age 16 to 65 years
• Complete spinal cord injury (ASIA A)
• Neurological level : C5 to T11
• MRI showing lesion

Exclusion Criteria:

• Women who are pregnant or breastfeeding
• Coma or other severe injury or disease
• Penetrating injury
• Ongoing mechanical ventilation
• Unsuitable based on MRI or other factor

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Improvement of ASIA grade

Secondary Outcome Measures

Outcome Measure
Sensory scores
Motor scores
Bladder and bowel function

Collaborators and Investigators

• Sponsor: Proneuron Biotechnologies
• Collaborators: The Marcus Foundation; B.I.R.D. (Israel-U.S. Binational Industrial Research and Development)
• Investigators: Study Director: Daniel Lammertse, M.D., Craig Hospital; Study Director: Nachshon Knoller, M.D., Chaim Sheba Medical Center; Study Director: Marca Sipski, M.D., University of Miami; Study Director: Edward Benzel, M.D., The Cleveland Clinic

Publications and helpful links

General Publications

• Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005 Sep;3(3):173-81. doi: 10.3171/spi.2005.3.3.0173.
• Bomstein Y, Marder JB, Vitner K, Smirnov I, Lisaey G, Butovsky O, Fulga V, Yoles E. Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 2003 Sep;142(1-2):10-6. doi: 10.1016/s0165-5728(03)00260-1.
• Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 1998 Jul;4(7):814-21. doi: 10.1038/nm0798-814.
• Lammertse DP, Jones LA, Charlifue SB, Kirshblum SC, Apple DF, Ragnarsson KT, Falci SP, Heary RF, Choudhri TF, Jenkins AL, Betz RR, Poonian D, Cuthbert JP, Jha A, Snyder DA, Knoller N. Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial. Spinal Cord. 2012 Sep;50(9):661-71. doi: 10.1038/sc.2012.39. Epub 2012 Apr 24.

Helpful Links

• www.spinalcordtrial.com

Study record dates

Study Major Dates

• Study Start: September 1, 2003

Study Registration Dates

• First Submitted: December 10, 2003
• First Submitted That Met QC Criteria: December 10, 2003
• First Posted (Estimate): December 11, 2003

Study Record Updates

• Last Update Posted (Estimate): August 28, 2009
• Last Update Submitted That Met QC Criteria: August 27, 2009
• Last Verified: March 1, 2006

More Information

Terms related to this study

• Keywords: tetraplegia; paralysis; nerve regeneration; paraplegia; quadraplegia; Acute, Complete SCI
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: 22-P-01