Clinical trial NCT02096913: Safety Study of Ibuprofen to Treat Acute Traumatic Spinal Cord Injury
Official title: The Rho-Inhibitor Ibuprofen for the Treatment of Acute Spinal Cord Injury: Investigation of Safety, Feasibility and Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Spinal Cord Injury
Keywords: Rho-Inhibition
Plasticity
Neurological Function
RhoA
Ibuprofen
NSAIDs
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Else Kröner Fresenius Foundation
First posted: 2014-03-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The Ibuprofen - Spinal Cord Injury (SCI) - Safety trial investigates tolerability and feasibility of "small molecule" (Ibuprofen) mediated Rho-inhibition as putative neuroprotective, plasticity-enhancing and neurorestaurative intervention. The primary safety analysis is based on the incidence of severe gastrointestinal bleedings. In addition, the feasibility of recruitment procedure, and oral administration of the compound within the multidisciplinary setting of acute intensive medical care will be explored. Furthermore, the pharmacokinetics of Ibuprofen under the condition of acute motor complete SCI will be investigated. Secondary endpoints will permit preliminary statements about effects on neuropathic pain, spasticity, and neurological function.


Eligibility criteria: Inclusion Criteria:

* Acute SCI of the cervical spine due to trauma
* Time frame of 4-21 days post-trauma
* Motor complete injury AIS A and B
* Neurological level of the lesion C4-T4
* No participation in a different clinical trial according to German Pharmaceuticals Act (AMG) 1 month before and during participation in the current trial
* The patient has been informed and his/her written consent has been obtained
* Age: 18 to 65 years
* For women of reproductive age: Negative pregnancy test and highly effective contraception (defined as Pearl Index \< 1) or sexual abstinence during participation in the trial

Exclusion Criteria:

* Multifocal lesions of the spinal cord
* Penetrating spinal cord injury
* Accompanying traumatic brain injury (TBI) with visible structural lesions including intracranial hemorrhage on diagnostic imagesSigni
* Significant accompanying injury to the peripheral nervous system, particularly plexus lesions
* Acute or chronic systemic diseases accompanied by neurological deficits or that have caused permanent neurological deficits which may overlay or hinder the registration of sensomotor functions (e.g. multiple sclerosis, Guillain-Barré syndrome, HIV infection, Lues etc.)
* Malignant neoplasms, except if these are in complete remission.
* Mental diseases or dementia which, in the investigator's opinion, limit the patient's cooperation in respect of the intake of the study medication and/or significantly hinder the registration of follow-up parameters
* Hemophilia
* History of myocardial infarction or stroke
* Current and persistent misuse of illegal drugs or alcohol
* Hypothermia below 35 C°
* Pregnancy and lactation
* All further contraindications to the study medication, including other ingredients of the pharmaceutical form according to the Summary of Product Characteristics (SPC)
* Known hypersensitivity to the active substance contained in the concomitant medication Pantoprazole or one of the components of the drug.
* Intake of Ibuprofen or intake of other active substances from the group of Nonsteroidal Anti-inflammatory Drugs (NSAIDs; e.g., Diclofenac, Indometacin) or the intake of NSAIDs in maximum recommended daily doses during one week prior to enrolment in the trial
* Simultaneous intake of salicylates, particularly acetylsalicylic acid
* Simultaneous intake of oral anticoagulants
* Simultaneous intake of systemic glucocorticoids
* Unwilling to consent to storage and transfer of pseudonymized medical data for the purpose of the clinical trial
* Admitted to an institution by a court or official order (pursuant to AMG §40 (1) 4)

Primary outcomes:
measure: Number of patients with severe gastroduodenal bleedings as a measure of safety
timeFrame: up to 4 months
Secondary outcomes:
measure: Spasticity on the Modified Ashworth Scale (MAS)
timeFrame: 4 weeks and 6 months
measure: Pain on the Neuropathic Pain Scale (NPS)
timeFrame: baseline, 4 weeks and 6 months
measure: International standards for neurological classification of spinal cord injury (ISNCSCI) - ASIA impairment scale (AIS) change from baseline
timeFrame: baseline, 4 weeks and 6 months
measure: Neurological motor function on the ISNCSCI/ASIA motor scores change from baseline
timeFrame: baseline, 4 weeks and 6 months
measure: Neurological sensory function on the ISNCSCI/ASIA sensory score change from baseline
timeFrame: baseline, 4 weeks and 6 months
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: up to 6 months
measure: Ibuprofen levels in plasma
timeFrame: Arm I (day 1 and week 4), Arm II (day 1, week 4 and 12) 1.5 and 3 hours post-dose
measure: Ibuprofen levels in cerebrospinal fluid (CSF)
timeFrame: Arm I (day 1 and week 4), Arm II (day 1, week 4 and 12) 3 hours post-dose
Other outcomes:
measure: Heterotopic ossifications
timeFrame: baseline, 4 weeks and 6 months
Locations:
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries, Warener Straße 7
Study officials:
affiliation: Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries, Germany
name: Andreas Niedeggen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité, Universitätsmedizin Berlin, Spinal Cord Injury Research, Germany
name: Jan M Schwab, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kopp MA, Liebscher T, Watzlawick R, Martus P, Laufer S, Blex C, Schindler R, Jungehulsing GJ, Knuppel S, Kreutztrager M, Ekkernkamp A, Dirnagl U, Strittmatter SM, Niedeggen A, Schwab JM. SCISSOR-Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol. BMJ Open. 2016 Jul 26;6(7):e010651. doi: 10.1136/bmjopen-2015-010651.