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Safety Study of Ibuprofen to Treat Acute Traumatic Spinal Cord Injury

Primary Purpose

Spinal Cord Injury

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Dolormin® extra (Ibuprofen)
Dolormin® extra (Ibuprofen)
Sponsored by
Jan M. Schwab, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring Rho-Inhibition, Plasticity, Neurological Function, RhoA, Ibuprofen, NSAIDs

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries, Warener Straße 7

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Dolormin® extra (Ibuprofen) 4 weeks

Dolormin® extra (Ibuprofen) 12 weeks

Arm Description

Outcomes

Primary Outcome Measures

Number of patients with severe gastroduodenal bleedings as a measure of safety
Safety of lbuprofen as measured by the occurence of severe gastroduodenal bleedings documented as serious adverse events (SAE)

Secondary Outcome Measures

Spasticity on the Modified Ashworth Scale (MAS)
Pain on the Neuropathic Pain Scale (NPS)
International standards for neurological classification of spinal cord injury (ISNCSCI) - ASIA impairment scale (AIS) change from baseline
Neurological motor function on the ISNCSCI/ASIA motor scores change from baseline
Neurological sensory function on the ISNCSCI/ASIA sensory score change from baseline
Number of participants with adverse events as a measure of safety and tolerability
Ibuprofen levels in plasma
Ibuprofen levels in cerebrospinal fluid (CSF)

Full Information

First Posted
March 24, 2014
Last Updated
October 26, 2017
Sponsor
Jan M. Schwab, MD, PhD
Collaborators
Else Kröner Fresenius Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02096913
Brief Title
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
June 2013 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jan M. Schwab, MD, PhD
Collaborators
Else Kröner Fresenius Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury
Keywords
Rho-Inhibition, Plasticity, Neurological Function, RhoA, Ibuprofen, NSAIDs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dolormin® extra (Ibuprofen) 4 weeks
Arm Type
Active Comparator
Arm Title
Dolormin® extra (Ibuprofen) 12 weeks
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Dolormin® extra (Ibuprofen)
Other Intervention Name(s)
Ibuprofen-DL-Lysinsalz
Intervention Description
Ibuprofen Tablets (as lysine-salt) 2400mg/d (400mg 2-2-2) applied orally for 4 weeks (Arm I; n=6). In order to reduce the risk of damage to the gastrointestinal mucosa Pantoprazole is applied as concomitant medication in a dosage 40mg/d during the treatment period.
Intervention Type
Drug
Intervention Name(s)
Dolormin® extra (Ibuprofen)
Other Intervention Name(s)
Ibuprofen-DL-Lysinsalz
Intervention Description
Ibuprofen Tablets (as lysine-salt) 2400mg/d (400mg 2-2-2) applied orally for 12 weeks (Arm II, n=6). In order to reduce the risk of damage to the gastrointestinal mucosa Pantoprazole is applied as concomitant medication in a dosage 40mg/d during the first 4 weeks of treatment and may be reduced to 20mg/d during the following treatment period after individual risk-benefit assessment.
Primary Outcome Measure Information:
Title
Number of patients with severe gastroduodenal bleedings as a measure of safety
Description
Safety of lbuprofen as measured by the occurence of severe gastroduodenal bleedings documented as serious adverse events (SAE)
Time Frame
up to 4 months
Secondary Outcome Measure Information:
Title
Spasticity on the Modified Ashworth Scale (MAS)
Time Frame
4 weeks and 6 months
Title
Pain on the Neuropathic Pain Scale (NPS)
Time Frame
baseline, 4 weeks and 6 months
Title
International standards for neurological classification of spinal cord injury (ISNCSCI) - ASIA impairment scale (AIS) change from baseline
Time Frame
baseline, 4 weeks and 6 months
Title
Neurological motor function on the ISNCSCI/ASIA motor scores change from baseline
Time Frame
baseline, 4 weeks and 6 months
Title
Neurological sensory function on the ISNCSCI/ASIA sensory score change from baseline
Time Frame
baseline, 4 weeks and 6 months
Title
Number of participants with adverse events as a measure of safety and tolerability
Time Frame
up to 6 months
Title
Ibuprofen levels in plasma
Time Frame
Arm I (day 1 and week 4), Arm II (day 1, week 4 and 12) 1.5 and 3 hours post-dose
Title
Ibuprofen levels in cerebrospinal fluid (CSF)
Time Frame
Arm I (day 1 and week 4), Arm II (day 1, week 4 and 12) 3 hours post-dose
Other Pre-specified Outcome Measures:
Title
Heterotopic ossifications
Description
Screening for heterotopic ossifications using sonography of the hip joints
Time Frame
baseline, 4 weeks and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Niedeggen, MD
Organizational Affiliation
Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan M Schwab, MD, PhD
Organizational Affiliation
Charité, Universitätsmedizin Berlin, Spinal Cord Injury Research, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries, Warener Straße 7
City
Berlin
ZIP/Postal Code
12683
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
27466236
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.
Results Reference
derived

Learn more about this trial

Safety Study of Ibuprofen to Treat Acute Traumatic Spinal Cord Injury

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