Trial document





This trial has been registered retrospectively.
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  DRKS00009917

Trial Description

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Title

Cytokine expression patterns in patients with traumatic Spinal Cord Injury

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Trial Acronym

SCI cytokine study

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

Current studies report an average of annual incidence of SCI in the United States of 40 cases per million (1). In Germany the acute traumatic SCI with following paraplegia the incidence constitutes ca. 1800 cases per year (2). Even though throughout the last years in order to understand the mechanisms and to explore new therapies many efforts in this field have been registered, a path breaking approach keeps missing. There is still no causal therapy that achieves an improvement of the neurological deficit (3). SCIs and resulting paraplegia impair patient’s quality of life in a huge dimension and cause immense financial consequences for them and their families (3),(4). The pathophysiological process is characterized by a primary and a secondary phase of injury. While the first phase is marked by a mechanical trauma the second one is more complex due to the variety of pathophysiological processes. It is reported that in consequence of a synergistic effect of proinflammatory cytokines the affected tissue is devastated (5),(6),(7),(8). So far it remains unclear whether the proinflammatory agency in the spinal cord overall features a positive or negative effect. Most studies used an animal protocol to investigate the secondary phase of injury. Several interesting results in terms of possible strategies against the formation of the glial scar and to improve the neuroregeneration have been published. Nevertheless the clinical research is more groundbreaking on grounds of animals’ blood and liquor values differ from humans and are most times not transferable (9). Important questions remain unanswered about how results from animal studies should be used and how data derived from them should be interpreted (10). Cytokines, a group of soluble peptides, are coordinators of the homeostasis. They regulate, on a systemic level, inflammatory reactions and acute-phase-reactions as well as wound healing as a part of the neuroimmunological network. They are released in- and outside of the CNS and cause especially local effects. They can be divided in groups with pro- and anti-inflammatory action profile. In our actual study we discovered that IL-8 and IL-10 are potential markers for the neurological remission and rehabilitation after traumatic spinal cord injury (11). Our ambition is the disclosure of a prognostic marker for the SCI based on a human protocol. This will provide two major advances. First we hope to come closer to a prognostic instrument for the clinical practice and second we are convinced that seeking for therapies a marker plays a major role as supervision. Studies need to be performed on larger groups of patients to validate the results. Our preliminary work needs to be extended to install a systematic database of specific cytokines in the peripheral serum and whole blood in correlation to the clinical outcome. Furthermore data will be analyzed using DBN and PCA network analysis to reveal activation patterns after traumatic spinal cord injury. In this context TNF-alpha, IL-1ß, IL-6, IL-8, IL-10, IFN-γ, VEGF, TGF-ß, IGF-1, PDGF, GH, sCD95L, BDNF, NT-3,-4, NGF, CNTF, HGF, MMP`s, steroids and minerals are needed to be analyzed. These parameters are in focus of recent publications therefore scientists and clinicians will benefit from a reliable prognosis marker after traumatic spinal cord injury.


References

1. Devivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal cord. 2012;50(5):365-72.

2. Schwab JM, Brechtel K, Conrad S, Schluesener HJ. From cell death to neuronal regeneration: building a new brain after traumatic brain injury (J Neuropathol Exp Neurol 2003;62:801-11. J Neuropathol Exp Neurol. 2004;63(2):180-1.

3. Rowland JW, Hawryluk GW, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus. 2008;25(5):E2.

4. Boakye M, Leigh BC, Skelly AC. Quality of life in persons with spinal cord injury: comparisons with other populations. J Neurosurg Spine. 2012;17(1 Suppl):29-37.

5. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118(2):503-8.

6. Kwon BK, Stammers AM, Belanger LM, Bernardo A, Chan D, Bishop CM, et al. Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury. J Neurotrauma. 2010;27(4):669-82.

7. Stammers AT, Liu J, Kwon BK. Expression of inflammatory cytokines following acute spinal cord injury in a rodent model. J Neurosci Res. 2012;90(4):782-90.

8. Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine (Phila Pa 1976). 2004;29(9):966-71.

9. Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. The Journal of Immunology. 2004;172(5):2731-8.

10. Kwon BK, Streijger F, Hill CE, Anderson AJ, Bacon M, Beattie MS, et al. Large animal and primate models of spinal cord injury for the testing of novel therapies. Experimental neurology. 2015;269:154-68.

11. Moghaddam A, Child C, Bruckner T, Gerner HJ, Daniel V, Biglari B. Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury. International journal of molecular sciences. 2015;16(4):7900-16.

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Organizational Data

  •   DRKS00009917
  •   2016/03/23
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  •   yes
  •   Approved
  •   S-514/2011, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

  •   U1111-1179-1620 
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Health Condition or Problem studied

  •   T09.3 -  Injury of spinal cord, level unspecified
  •   G95.9 -  Disease of spinal cord, unspecified
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Interventions/Observational Groups

  •   Patients with traumatic Spinal Cord Injury fulfilling the inclusion criteria are included in the study. According to the Neurological Remission patients are divided in two Groups (G1=Patients with Neurological Remission and G2=Patients without Neurological Remission). Blood is drawn at the same time points in the studies for both groups. Four vials of blood Serum and one whole blood vial (each 7.5 ml) are obtained according to a fixed schema i.e. 4, 9, 12 hours, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after the trauma Event and analyzed.
    Patients of group G1 are included in Arm 1.
  •   Patients of group G2 are included in Arm 2.
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Characteristics

  •   Non-interventional
  •   Other
  •   Other
  •   Open (masking not used)
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  •   Other
  •   Prognosis
  •   Other
  •   N/A
  •   No
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Primary Outcome

ASIA score* after 3 months

*This is a system of tests used to define and describe the extent and severity of a patient’s spinal cord injury and help determine future rehabilitation and recovery needs. The patient’s grade is based on how much sensation he or she can feel at multiple points on the body, as well as tests of motor function.

ASIA (ASIA Impairment Scale)
Grade A
Complete lack of motor and sensory function below the level of injury (including the anal area)
Grade B
Some sensation below the level of the injury (including anal sensation)
Grade C
Some muscle movement is spared below the level of injury, but 50 percent of the muscles below the level of injury cannot move against gravity.
Grade D
Most (more than 50 percent) of the muscles that are spared below the level of injury are strong enough to move against gravity.
Grade E
All neurologic function has returned.

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Secondary Outcome

Neurological Remission according to ASIA Score after 3 months (Examinating wheather the patient had a neurological improvement or not)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2012/07/25
  •   130
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   no maximum age
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Additional Inclusion Criteria

Patient with acute traumatic Spinal Cord Injury

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Exclusion Criteria

non-traumatic spinal cord injury, traumatic brain injury (TBI), severe abdominal trauma, traumatic amputation of extremities and coma. Participants were given neither methylprednisolone sodium succinate (MPSS) nor nonsteroidal anti-inflammatory drugs (NSAIDs) during study participation.

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Addresses

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    • Oberarzt der Unfall- und Wiederherstellungschirurgie Universitätsklinik Heidelberg Department für Orthopädie, Unfallchirurgie und Paraplegiologie
    • Mr.  Prof. Dr. med.  Arash  Moghaddam 
    • Schlierbacher Landstraße 200a
    • 69118  Heidelberg
    • Germany
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    • HTRG Heidelberg Trauma Research GroupDepartment für Orthopädie, Unfallchirurgie und Paraplegiologie
    • Mr.  cand. med.  Raban  Heller 
    • Schlierbacher Landstraße 200a
    • 69118  Heidelberg
    • Germany
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    • HTRG Heidelberg Trauma Research GroupDepartment für Orthopädie, Unfallchirurgie und Paraplegiologie
    • Mr.  cand. med.  Raban  Heller 
    • Schlierbacher Landstraße 200a
    • 69118  Heidelberg
    • Germany
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Sources of Monetary or Material Support

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    • Heidelberg Trauma Research Group, Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and SpinalCord Injury, Heidelberg University Hospital
    • Mr.  Prof. Dr. med.  Arash  Moghaddam 
    • Schlierbacher Landstraße 200a
    • 69118   Heidelberg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

  •   Summary
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* This entry means the parameter is not applicable or has not been set.