Clinical trials and tribulations: lessons from spinal cord injury studies registered on ClinicalTrials.gov.

STUDY DESIGN: Article. OBJECTIVE: ClinicalTrials.gov is an online trial registry that provides public access to information on past, present, and future clinical trials. While increasing transparency in research, the quality of the information provided in trial registrations is highly variable. The objective of this study is to assess key areas of information on ClinicalTrials.gov in interventional trials involving people with spinal cord injuries. SETTING: Interventional trials on ClinicalTrials.gov involving people with spinal cord injuries. METHODS: A subset of data on interventional spinal cord injury trials was downloaded from ClinicalTrials.gov. Reviewers extracted information pertaining to study type, injury etiology, spinal cord injury characteristics, timing, study status, and results. RESULTS: Of the interventional trial registrations reviewed, 62.5%, 58.6%, and 24.3% reported injury level, severity, and etiology, respectively. The timing of intervention relative to injury was reported in 72.8% of registrations. Most trials identified a valid study status (89.2%), but only 23.5% of those completed studies had posted results. CONCLUSIONS: Our review provides a snapshot of interventional clinical trials conducted in the field of spinal cord injury and registered in ClinicalTrials.gov. Areas for improvement were identified with regards to reporting injury characteristics, as well as posting results.

Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury.

Context: Following spinal cord injury (SCI) at the cervical or upper-thoracic level, orthostatic hypotension (OH) is observed in 13-100% of patients. This study aimed to test the feasibility of conducting a randomized controlled trial combining a dynamic tilt-table (Erigo®) and functional electrical stimulation (FES) to mitigate OH symptoms in the subacute phase after SCI. Design: Pilot study. Setting: A tertiary rehabilitation hospital. Participants: Inpatients who had a C4-T6 SCI (AIS A-D) less than 12 weeks before recruitment, and reported symptoms of OH in their medical chart. Interventions: Screening sit-up test to determine eligibility, then 1 assessment session and 3 intervention sessions with Erigo® and FES for eligible participants. Outcome measures: Recruitment rate, duration of assessment and interventions, resources used, blood pressure, and Calgary Presyncope Form (OH symptoms). Results: Amongst the 232 admissions, 148 inpatient charts were reviewed, 11 inpatients met all inclusion criteria, 7 participated in a screening sit-up test, and 2 exhibited OH. Neither of the two participants recruited in the pilot study was able to fully complete the assessment and intervention sessions due to scheduling issues (i.e. limited available time). Conclusion: This pilot study evidenced the non-feasibility of the clinical trial as originally designed, due to the low recruitment rate and the lack of available time for research in participant's weekday schedule. OH in the subacute phase after SCI was less prevalent and less incapacitating than expected. Conventional management and spontaneous resolution of symptoms appeared sufficient to mitigate OH in most patients with subacute SCI.

An inclusive, online Delphi process for setting targets for best practice implementation for spinal cord injury.

RATIONALE, AIMS, AND OBJECTIVES: The Spinal Cord Injury Knowledge Mobilization Network is a pan-Canadian community of practice composed of seven rehabilitation hospitals. The goal of this network is to utilize implementation science processes to facilitate the adoption of best practice in spinal cord injury (SCI) rehabilitation. In addition to selecting specific practices for implementation, a key aspect of effective implementation is the engagement of stakeholders in decision-making processes. To achieve this, the network utilized a Delphi process to reach consensus on two pressure ulcer prevention and management practices to be implemented in SCI inpatient rehabilitation. A diverse, multidisciplinary panel of clinicians, researchers, sponsoring agency representatives, and persons with SCI participated in this process. METHOD: An online Delphi process was conducted in order to prioritize pressure ulcer prevention and management best practice recommendations and performance indicators for implementation. The process was conducted in six stages: (1) steering committee selection; (2) identification and selection of evidence; (3) participant selection and recruitment; (4) survey development; (5) identification of voting criteria; and (6) five rounds of voting. RESULTS: The Delphi process resulted in the selection of two best practices: (1) comprehensive risk assessment and (2) education for pressure ulcer prevention and management in persons with SCI. CONCLUSIONS: In this Delphi process, a large expert panel achieved consensus on best practice recommendations and associated performance indicators for implementation. This process was undertaken as a first step towards optimization of service delivery and outcomes for persons with SCI across Canada.

Neuropathic pain post spinal cord injury part 1: systematic review of physical and behavioral treatment.

BACKGROUND: Neuropathic pain has various physiologic and psychosocial aspects. Hence, there is a growing use of adjunct nonpharmacological therapy with traditional pharmacotherapy to reduce neuropathic pain post spinal cord injury (SCI). OBJECTIVE: The purpose of this study was to conduct a systematic review of published research on nonpharmacological treatment of neuropathic pain after SCI. METHODS: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing nonpharmacological treatment of pain post SCI. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a treatment or intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention was being studied. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale. RESULTS: The 16 articles selected for this review fell into 1 of 2 categories of nonpharmacological management of pain after SCI: physical and behavioral treatments. The pooled sample size of all studies included 433 participants. Of the 16 studies included, 7 were level 1, 3 were level 2, and 6 were level 4 studies. CONCLUSIONS: Physical interventions demonstrated the strongest evidence based on quality of studies and numbers of RCTs in the nonpharmacological treatment of post-SCI pain. Of these interventions, transcranial electrical stimulation had the strongest evidence of reducing pain. Despite a growing body of literature, there is still a significant lack of research on the use of nonpharmacological therapies for SCI pain.

Neuropathic pain post spinal cord injury part 2: systematic review of dorsal root entry zone procedure.

BACKGROUND: Pharmacotherapy may not sufficiently reduce neuropathic pain in many individuals post spinal cord injury (SCI). The use of alternative therapies such as surgery may be effective in reducing neuropathic pain in these individuals. However, because of the invasive nature of surgery, it is important to examine the evidence for use of this treatment. OBJECTIVE: The purpose of this study was to conduct a systematic review of published literature on the surgical treatment of neuropathic pain after SCI. METHODS: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles in which surgical treatment of pain after SCI was examined. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a surgical intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention involving the dorsal root entry zone (DREZ) procedure was used to reduce pain. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale. RESULTS: Eleven studies met the inclusion criteria. One study provided level 2 evidence, and the rest provided level 4 evidence. The DREZ procedure was shown to be more effective for segmental pain than for diffuse pain after SCI. Further, individuals with conus medullaris level injury were found to have a higher level of neuropathic pain relief than those with cervical, thoracic, or cauda equina injury. CONCLUSIONS: The studies demonstrated that the DREZ procedure may be effective in reducing segmental pain. Hence, DREZ may be important in treatment of neuropathic pain in individuals resistant to less invasive treatments. Because the studies lacked control conditions and examination of long-term effects, there is a need for larger trials with more stringent conditions.

The health and life priorities of individuals with spinal cord injury: a systematic review.

Determining the priorities of individuals with spinal cord injury (SCI) can assist in choosing research priorities that will ultimately improve their quality of life. This systematic review examined studies that directly surveyed people with SCI to ascertain their health priorities and life domains of importance. Twenty-four studies (a combined sample of 5262 subjects) that met the inclusion criteria were identified using electronic databases (Medline, EMBASE, CINAHL, and PsycINFO). The questionnaire methods and domains of importance were reviewed and described. While the questionnaires varied across studies, a consistent set of priorities emerged. Functional recovery priorities were identified for the following areas: motor function (including arm/hand function for individuals with tetraplegia, and mobility for individuals with paraplegia), bowel, bladder, and sexual function. In addition, health, as well as relationships, emerged as important life domains. The information from this study, which identified the priorities and domains of importance for individuals with SCI, may be useful for informing health care and research agenda-setting activities.

A systematic review of pharmacologic treatments of pain after spinal cord injury.

OBJECTIVE: To conduct a systematic review of published research on the pharmacologic treatment of pain after spinal cord injury (SCI). DATA SOURCES: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database (PEDro) assessment scale, whereas non-RCTs were assessed by using the Downs and Black (D&B) evaluation tool. A level of evidence was assigned to each intervention by using a modified Sackett scale. STUDY SELECTION: The review included RCTs and non-RCTs, which included prospective controlled trials, cohort, case series, case-control, pre-post studies, and post studies. Case studies were included only when there were no other studies found. DATA EXTRACTION: Data extracted included the PEDro or D&B score, the type of study, a brief summary of intervention outcomes, the type of pain, the type of pain scale, and the study findings. DATA SYNTHESIS: Articles selected for this particular review evaluated different interventions in the pharmacologic management of pain after SCI. Twenty-eight studies met inclusion criteria; there were 21 randomized controlled trials; of these, 19 had level 1 evidence. Treatments were divided into 5 categories: anticonvulsants, antidepressants, analgesics, cannabinoids, and antispasticity medications. CONCLUSIONS: Most studies did not specify participants' types of pain, making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (5 level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain as did intravenous analgesics (lidocaine, ketamine, and morphine), but the latter only had short-term benefits. Tricyclic antidepressants only showed benefit for neuropathic pain in depressed persons. Intrathecal baclofen reduced musculoskeletal pain associated with spasticity; however, there was conflicting evidence for the reduction in neuropathic pain. Studies assessing the effectiveness of opioids were limited and revealed only small benefits. Cannabinoids showed conflicting evidence in improving spasticity-related pain. Clonidine and morphine when given together had a significant synergistic neuropathic pain-relieving effect.

Pharmacokinetic studies of single and multiple oral doses of fampridine-SR (sustained-release 4-aminopyridine) in patients with chronic spinal cord injury.

Fampridine (4-aminopyridine) is a potassium channel blocking agent that restores conduction in demyelinated axons and improves neurologic function in patients with chronic spinal cord injury (SCI). Based on the pharmacokinetic profile of orally administered fampridine, multiple daily doses (4 or more) would need to be taken to sustain its therapeutic effects. Two studies were conducted to determine the pharmacokinetics and safety profile of an oral, sustained-release (SR) formulation of fampridine (fampridine-SR, 10-25 mg) administered as a single dose (n = 14) and twice daily for 1 week (n = 16) in patients with chronic, incomplete SCI. Mean plasma concentrations and area under the plasma concentration-time curve were proportional to the dose administered, whereas other pharmacokinetic parameters were independent of dose. Fampridine-SR was absorbed slowly (peak plasma concentration shortly after dosing, 2.6-3.7 hours) and eliminated (plasma half-life, 5.6-7.6 hours), and reached steady state after 4 days of twice-daily administration. Fampridine-SR was well tolerated, with only mild to moderate adverse events reported, and no serious adverse events. The extended plasma half-life of fampridine-SR allows convenient twice-daily dosing. Clinical trials designed to assess neurologic and functional improvement using fampridine-SR in patients with chronic SCI are currently underway.