Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal cord-injured men Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury Efficacy and safety of tadalafil in men with erectile dysfunction following spinal cord injury. A Placebo-Controlled, Multicenter, Randomized, Double-Blind, Flexible-Dose,Two-Way Crossover Study to Evaluate the Efficacy and Safety of Sildenafil in Men With Traumatic Spinal Cord Injury and Erectile Dysfunction Vardenafil Improves Ejaculation Success Rates and Self-confidence in Men With Erectile Dysfunction due to Spinal Cord Injury Sildenafil efficacy in erectile dysfunction secondary to spinal cord injury depends on the level of cord injuries. Up-titration of vardena fi l dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury. Efficacy, safety and predictive factors of therapeutic success with sildenafil for erectile dysfunction in patients with different spinal cord injuries Quality of life in patients with spinal cord injury receiving VIAGRA® (sildenafil citrate) for the treatment of erectile dysfunction Prospective comparison of topical minoxidil to vacuum constriction device and intracorporeal papaverine injection in treatment of erectile dysfunction due to spinal cord injury. Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury. Spinal Cord Injury Rehabilitation Evidence: Methods of the SCIRE Systematic Review. Neuropathic pain post spinal cord injury part 1: systematic review of physical and behavioral treatment. Efficacy and safety of oral sildenafil (Viagra) in men with erectile dysfunction caused by spinal cord injury Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial. A two-part pilot study of sildenafil (VIAGRATM) in men with erectile dysfunction caused by spinal cord injury Risk factors predicting upper urinary tract deterioration in patients with spinal cord injury: a prospective study Safety and efficacy of vardenafil in patients with erectile dysfunction: result of a bridging study in Japan. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial Rho Inhibitor VX-210 in Acute Traumatic Subaxial Cervical Spinal Cord Injury: Design of the SPinal Cord Injury Rho INhibition InvestiGation (SPRING) Clinical Trial A Review of Clinical Trials in Spinal Cord Injury Including Biomarkers. Chapter 46 Pain following spinal cord injury.
Study design : Open , before – after study . Objective : To assess the efficacy and safety of phosphodiesterase type 5 ( PDE5 ) inhibitors for erectile dysfunction ( ED ) in spinal cord-injured ( SCI ) patients . Setting : Home- and clinic-based assessment s in the outpatient department at the Centre Bouffard Vercelli , Cerbère France . Methods : Clinic trials with Sildenafil ( Viagra ® )  on 120 patients , Tadalafil ( Cialis ® ) on 54 patients and Vardenafil ( Levitra ® ) on 66 patients were performed . Flexible doses of PDE5 inhibitors were given depending on efficacy and tolerability , from 50 to 100 mg for Sildenafil , and from 10 to 20 mg for Vardenafil and Tadalafil . Each trial was performed after a week 's interval . The efficacy was self-assessed by the patients on a six-point quantitative scale assessment . The response to treatment was assessed at home in 90 patients ( 57 patients on Sildenafil , 12 patients on Vardenafil and 21 patients on Tadalafil )  using the International Index of Erectile Function ( IIEF ) . Results : In clinic trials , PDE5 inhibitors were effective ( rigidity enough for penetration ) in 85 % of the patients on Sildenafil , 74 % of the patients on Vardenafil and 72 % of the patients on Tadalafil .  The mean duration of erection was 34 , 28 and 26 min , respectively . Adverse effects were mild , usually attenuated with continued dosing . More than 70 % of the patients on Vardenafil and Tadalafil required higher doses of 20 mg , whereas 50 mg of Sildenafil was effective in 55 % of the patients . Two-thirds of our patients on Tadalafil reported a duration of action longer than 24 h. The presence of an upper motor neuron lesion was significantly associated with therapeutic success , lower motor neuron lesions and cauda equina patients were poor responders . Other variables such as completeness of lesion had no impact . In the follow-up visits , the IIEF global scores and three IIEF domains ( erectile function , intercourse satisfaction and overall satisfaction ) were significantly improved in all patients . Patients on Sildenafil showed a significant improvement of orgasmic function , ejaculation ( Question 9 ) and orgasm ( Question 10 ) . Conclusion : Sildenafil , Vardenafil and Tadalafil are all effective and well-tolerated treatments for ED in SCI patients . Although no statistical analysis could be applied on these data , these results might indicate that Sildenafil is more effective in treating ED . Clinic trials are important for proper dose titration and appropriate education of the patients Objective : To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction ( ED ) due to traumatic spinal cord injury ( SCI ) . Methods : In this multicenter , double-blind , placebo-controlled , parallel-group 12-week study , 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were r and omized to vardenafil ( n = 207 ) or placebo ( n = 211 ) ( 10 mg for 4 weeks , then maintained or titrated to 5 or 20 mg at weeks 4 and 8) . Efficacy assessment s included the erectile function ( EF ) domain score of the International Index of Erectile Function question naire and diary questions regarding penetration , maintenance of erection to completion of intercourse , and ejaculation . Results : Baseline patient characteristics were similar in the vardenafil ( mean age 40 years ) and placebo ( mean age 39 years ) groups . Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 ( moderate ED ) in the placebo group . EF domain score in the vardenafil group improved to 22.0 ( mild ED ) at last observation carried forward vs 13.5 in the placebo group ( p < 0.001 ) . Over 12 weeks of treatment , mean per-patient penetration ( 76 % vs 41 % ) , maintenance ( 59 % vs 22 % ) , and ejaculation ( 19 % vs 10 % ) success rates were significantly greater vs placebo ( all p < 0.001 ) . The most frequently reported drug-related adverse events were headache ( vardenafil 15 % , placebo 4 % ) , flushing ( vardenafil 6 % , placebo 0 % ) , nasal congestion ( vardenafil 5 % , placebo 0 % ) , and dyspepsia ( vardenafil 4 % , placebo 0 % ) . Conclusion : Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury OBJECTIVE To determine the efficacy and safety of tadalafil when taken on dem and by men with erectile dysfunction ( ED ) secondary to traumatic spinal cord injury ( SCI ) . DESIGN AND SETTING Multicenter , r and omized , double-blind , placebo-controlled , flexible dose-titration , parallel-group study in clinical practice s in Europe . Patients Enrolled patients had ED secondary to SCI ( all spinal levels ) and sustained 6 months or longer before visit 1 . INTERVENTIONS After a 4-week run-in period , patients were r and omly assigned to tadalafil , 10 mg , ( n = 142 ) or placebo  ( n = 44 ) for a 12-week , on-dem and treatment period with assessment s at 4-week intervals . The dose of tadalafil was maintained or titrated ( 10 or 20 mg ) at 4 and 8 weeks . MAIN OUTCOME MEASURES Efficacy was measured using the International Index of Erectile Function ( IIEF ) , Sexual Encounter Profile ( SEP ) , and Global Assessment Question ( GAQ ) . Treatment-emergent adverse events and vital signs were collected at each visit . RESULTS Mean age was 38 years .  Mean baseline IIEF erectile function domain score was 13.4 , and following 12 weeks of treatment , 22.6 for tadalafil and 13.6 for placebo ( P < .001 ) . After treatment , the tadalafil group compared with the placebo group was significantly greater ( P < .001 ) in mean per-patient percentage of successful penetration attempts ( SEP question 2 ; 75.4 % vs 41.1 % ) and intercourse attempts ( SEP question 3 ; 47.6 % vs 16.8 % ) ; percentage of improved erections ( GAQ question 1 ; 84.6 % vs 19.5 % ) ; and ejaculatory frequency ( IIEF question 9 ; P = .03 ) . The 2 most common treatment-emergent adverse events in the tadalafil group compared with placebo were headache ( 8.5 % vs 4.5 % ) and urinary tract infection ( 7.7 % vs 6.8 % ) . CONCLUSIONS Tadalafil ( 10 mg and 20 mg ) improved erectile function and was well tolerated by men with ED secondary to traumatic SCI Abstract Background / objective : To show the efficacy , safety , and tolerability of sildenafil in men with erectile dysfunction ( ED ) associated with complete or incomplete spinal cord injury ( SCI ) and to assess its effects on quality of life ( Qol ) using the Life-Satisfaction Check List . Methods : This was a placebo-controlled , multicenter , r and omized , double-blind , flexible-dose , 2-way crossover study with a 2-week washout period between each phase . Patients with ED attributable to SCI(Sexual Health Inventory-Male score ≤21 ) received 50 to 100 mg sildenafil ( n = 24 ) or placebo ( n = 26 ) . Results : Compared with placebo , sildenafil produced higher levels of successful sexual stimulation , intercourse success , satisfaction with sexual life and sexual relationship , erectile function , overall sexual satisfaction , and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score , with no clinical ly relevant effects onvital signs . Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI , producing significant improvements , compared with placebo , in a number of measures only in patients with incomplete SCI . All patients who expressed a preference selected sildenafil over placebo , although the drug had no effect on patient Qol .  Sildenafil was well tolerated , with a profile comparable to that of placebo . Conclusions : Compared with placebo , treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI , especially in those with incomplete injury , and was theagent of choice in those who expressed a preference Study Design . Multicenter , double-blind , placebo-controlled , parallel-group study . Objective . To assess the effect of the oral phosphodiesterase type-5 inhibitor , vardenafil , on ejaculation rates and self-confidence in men with spinal cord injury ( SCI ) . Summary of Background Data . Spinal comm and of male sexual functions is often seriously impaired by traumatic spinal cord injury ( SCI ) . A high proportion of men with SCI can not ejaculate during sexual intercourse . SCI-related ejaculatory disorders are often responsible for male infertility . Sexual dysfunction associated with SCI can also affect men 's self-confidence . Methods . In this 12-week study , 418 men aged ≥18 years with erectile dysfunction > 6 months result ing from a traumatic SCI were r and omized to vardenafil ( n = 207 ) or placebo ( n = 211 ) 10 mg for 4 weeks , then maintained or titrated to 5 or 20 mg at weeks 4 and 8 . Assessment s included questions of the International Index of Erectile Function ( IIEF ) about ejaculation success and orgasmic perception ; the Global Confidence Question ; and quality -of-life scales to measure psychological well-being , self-esteem , depression , and mental health status . Results . Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment ( 19 % vs. 10 % ; P < 0.001 ) . At last observation carried forward , the IIEF “ orgasmic function ” score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo . Sixteen percent of men receiving vardenafil and 8 % receiving placebo felt orgasm “ almost always ” or “ always ” at weeks 8–12 , compared with 4 % and 6 % , respectively , at baseline . Significant improvements in confidence scores were observed with vardenafil compared with placebo ( P < 0.0001 ) . There were no clinical ly significant differences between vardenafil and placebo in the quality -of-life measures at the study endpoint , but these had been in the normal range at baseline . Conclusion . Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction ( ED ) secondary to upper motor neuron ( UMN ) and lower motor neuron ( LMN ) spinal cord injury ( SCI ) . After taking consents 105 patients suffering from ED were enrolled in this prospect i ve study . Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed ( UMN and LMN ) spinal cord injuries . The patients took 50 - 100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse . Based on a IIEF question naire , success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries . In patients with UMN disease , sildenafil was effective in 82 % of patients and its efficacy was statistically higher than placebo ( 82 vs. 25 % , p < 0.05 ) . Twenty-eight per cent of patients with non-UMN disease had a favourable response to sildenafil that was not statistically different from placebo . Sildenafil seems more effective in the treatment of  neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury . Actually , its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms AIM Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction ( ED ) . Efficacy of vardenafil has been demonstrated in various ED population s , but that in Japanese patients with spinal cord injury ( SCI ) has not been assessed . METHODS This was an open-label , multicenter , flexible dose , 12-week study in patients with ED due to SCI . Following a 4-week observation period , patients received vardenafil 10 mg for 4 weeks , and based on efficacy , tolerability and patient preference , doses for the remaining 8 weeks were decided by investigators . The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function . RESULTS Ten patients took 10 mg all through the study , while 22 patients took 20 mg after completing 4 weeks ' treatment with 10 mg . The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward ( LOCF ) in the former group and from 10.3 to 22.5 in the latter group , respectively . Importantly , there was a 5.0 point increase in erectile function domain score after up-titration in the latter group . Drug-related adverse events were observed in 22 % of patients including hot flushes ( 9 % ) and headache ( 6 % ) , but these were transient and mild in intensity . Serious adverse events and adverse events leading to discontinuation of the study drug were not reported . CONCLUSIONS Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI . Of interest , erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg Study design : Multicenter , open , prospect i ve , before-after study . Objective : To assess the efficacy and safety of sildenafil therapy for erectile dysfunction in patients with spinal cord injury , and the association between the response to sildenafil and factors such as causes and levels of spinal cord injury , grade of ASIA deficit , time since injury , orgasmic perception , and degree of baseline erection . Setting : Homes of out patients of 16 spinal cord injury units in Spain . Method : One hundred and seventy patients with erectile dysfunction secondary to spinal cord injury , from whom baseline data were collected on their sexual function , and who started treatment with sildenafil 50 mg .  An efficacy assessment was made by the patient and his partner , and the score of the International Index of Erectile Function ( IIEF ) was recorded . Results : It was reported by 88.2 % of the patients and 85.3 % of their partners that treatment with sildenafil had improved their erections , regardless of the baseline characteristics of the spinal cord injury and erectile function . In responders , this improvement was confirmed by an increase from 12.5 to 24.8 points ( P<0.001 ) of the Erectile Function Domain of IIEF . A significant improvement was also seen in patients ' satisfaction with sexual activity and general satisfaction derived from sexual life . Preservation of orgasmic perception and a baseline degree of erection of 3 or 4 ( P=0.006 ) were predictors of therapeutic success . No serious adverse events occurred . Conclusion : Sildenafil is an effective , well-tolerated treatment for erectile dysfunction caused by spinal cord injury , regardless of the cause , neurological level , ASIA grade , and time since injury . Sponsorship : Spanish Society of Paraplegia . Spinal Cord ( 2001 ) 39 , 637–643 Study design : A multicenter , r and omized , double-blind , placebo-controlled , flexible-dose , two-way crossover study conducted June 1996 through January 1997 . Objectives : To evaluate the effect of sildenafil citrate ( VIAGRA ® ) on the quality of life ( QoL ) of men with erectile dysfunction ( ED ) caused by spinal cord injury ( SCI ) . Setting : Study centers in Australia , Belgium , France , Germany , Norway , Sweden and the United Kingdom . Methods : Questions 13 and 14 of the 15-item International Index of Erectile Function ( IIEF ) addressed QoL issues directly related to ED in 178 men with SCI . A 5-item question naire addressing concerns that men had about their erection problems was also used to evaluate the impact of ED on QoL. Several commonly used psychometric instruments , including the Medical Outcomes Survey ( MOS ) Short Form-12 , Psychological General Well-Being Index , and MOS Family Survey , assessed general QoL issues . Results : Significant improvements were seen for overall satisfaction with sex life ( IIEF Q13 ) , sexual relationship with partner ( IIEF Q14 ) , and concerns about erectile problems ( P<0.0001 ) . Improvements were reported in scores for the generic QoL parameters of mental health , well-being , depression , and anxiety ( P<0.05 sildenafil versus placebo ) . Conclusion : Treatment with sildenafil can significantly improve key QoL parameters in men with ED caused by SCI.Sponsorship : This study was funded by Pfizer OBJECTIVE To compare the effectiveness of topically applied 2 % minoxidil to that of intracorporeal injection therapy and vacuum constriction devices for the treatment of  erectile dysfunction in the spinal cord injured ( SCI ) male . METHODS Eighteen SCI men , aged nineteen to sixty-five years ( median age , 29 ) , and level of injury C7 to L3 ( 15 thoracic level ) were prospect ively evaluated . All patients were able to achieve only a poorly sustained reflex erection that was inadequate for satisfactory intercourse . No patient had suffered erectile dysfunction prior to his SCI . In each patient , 1 mL of a 2 % minoxidil solution was applied as an aerosol spray to the glans penis . The erectile response was compared to that obtained with a vacuum constriction device ( VCD ) and intracorporeal papaverine injection . In each case , the subjective assessment by both the patient and the physician , as well as objective results of penile base rigidity as measured by the RigiScan DT Monitor Device , were recorded . RESULTS Papaverine increased rigidity at the base of the penis by a median 77 percent ( range , 30 - 100 % ) . The VCD increased rigidity by a median 57 percent ( range , 30 - 80 % ) . Minoxidil induced no change in rigidity ( range , 0 - 15 % ) . No complications were observed for any method of inducing tumescence . CONCLUSIONS Papaverine and VCD proved to be effective means of establishing penile erection in male SCI patients . Both subjective and objective erectile responses to minoxidil were poor . Nevertheless , the principle of topical therapy is an attractive alternative to existing modalities . Further investigation is warranted OBJECTIVES To assess the efficacy of intraurethral prostagl and in E1 ( alprostadil , MUSE ) in treating  erectile dysfunction in patients with spinal cord injury ( SCI ) . METHODS Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction . All patients were at least 1 year after injury , and all had previously used intracavernosal injections successfully ( Schramek 's grade 5 erection ) . The intraurethral drug was administered in the office , in the presence of a physician , with monitoring of blood pressure . If effective , the patient was then able to use MUSE at home . The first 3 patients underwent gradual dose escalation starting with 125 microg , without the use of a constriction ring . Because of hypotension , the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg . The quality of the erection was compared with that achieved with intracavernosal injections using Schramek 's grading . RESULTS The dose escalation ( titration ) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response . Transient hypotension was noted in these first 3 patients in whom the constricting b and was not used . The highest dose of MUSE ( 1000 microg ) was , therefore , used in the remaining 12 patients , with the constriction b and . The quality of the erection varied and appeared to be less rigid in all patients ( 12 patients with grade 1 to 3 ; 3 patients with grade 4 ) than that noted with intracavernosal injection therapy ( 1 5 patients with grade 5 ) . There was no incidence of priapism . The 3 patients with grade 4 erections tried the MUSE at home . All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy . CONCLUSIONS MUSE appears to be somewhat effective in creating erections ; however , these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction . It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension . Its ultimate use depends on the patient 's level of satisfaction with the quality of the erection compared with intracavernosal injections The Spinal Cord Injury Rehabilitation Evidence ( SCIRE ) is a synthesis of the research evidence underlying rehabilitation interventions to improve the health of people living with SCI . SCIRE covers a comprehensive set of topics and in this issue we present six papers relevant to SCI rehabilitation clinicians ( SCI inpatient rehabilitation practice s , gait strategies , upper extremity reconstructive surgery , spasticity treatments , cardiovascular health and bone health ) . The SCIRE used a systematic and well-defined protocol to assess and synthesize the evidence . Each article was scored for its method ological quality using either the Physiotherapy Evidence Data base ( PEDro ) Score for r and omized controlled trials or the Downs and Black Tool for other types of studies . Following the individual study assessment , conclusions were drawn about the accumulated studies for each topic of interest based on the levels of evidence , quality of studies and concurring evidence . The SCIRE project was design ed for health professionals to inform them of best practice 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 data bases were search ed for articles addressing nonpharmacological treatment of pain post SCI . Articles were restricted to the English language . Article selection was conducted by 2 independent review ers 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 . R and omized controlled trials ( RCTs ) were assessed for quality using the Physiotherapy Evidence Data base ( 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 Objective : To evaluate the efficacy and safety of 50-mg doses of sildenafil during a 28-day period in patients with erectile dysfunction caused by spinal cord injury ( cord level range , T6 through L5 ) . Background : Sildenafil is an orally active , potent , and selective inhibitor of phosphodiesterase type 5 , an important regulator of cyclic guanosine monophosphate in the human corpus cavernosum . Methods : To be included in this double-blind , placebo-controlled study , all patients had to be able to achieve at least a partial reflexogenic erectile response to penile vibratory stimulation . The study utilized a single triangular sequential trial design . A total of 27 patients were r and omized to receive 50 mg of sildenafil or placebo , taken orally as required ( not more than once daily ) approximately 1 hour before sexual activity . Results : After 28 days of treatment , nine of 12 patients ( 75 % ) on sildenafil and one of 14 patients ( 7 % ) on placebo reported that treatment had improved their erections ( p = 0.0043 ) . Furthermore , eight of 12 patients ( 67 % ) on sildenafil and two of 13 patients ( 15 % ) on placebo indicated that they wished to continue treatment ( p = 0.018 ) . A significant improvement in satisfaction with their sex life was reported by patients taking sildenafil ( p = 0.012 ) . No patients discontinued treatment due to adverse events . Conclusion : Oral sildenafil , taken as required ( not more than once daily ) , significantly improves the quality of erections and satisfaction with sex life in men with erectile dysfunction caused by a spinal cord injury between T6 and L5 In the immediate period after traumatic spinal cord injury ( SCI ) a variety of secondary injury mechanisms combine to gradually exp and the initial lesion size , potentially leading to diminished neurological outcomes at long-term follow-up . Riluzole , a benzothiazole drug , which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity , is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis . Moreover , several pre clinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation . Based on these findings , riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI . Currently , a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network ( NACTN ) for Treatment of Spinal Cord Injury . The current review summarizes the existing pre clinical and clinical literature on riluzole , provides a detailed description of the Phase I trial , and suggests potential opportunities for future investigation . Clinical trial registration no. : NCT00876889 Study design : This was a two-part pilot study in men with erectile dysfunction ( ED ) due to spinal cord injury ( SCI : cord level range T6-L5 ) . Part I was a r and omised , double-blind , two-way cross-over study comparing a single dose of sildenafil 50 mg or placebo . Part II was a r and omised , double-blind , parallel-group evaluation of sildenafil 50 mg or placebo , taken as required ( not more than once daily ) approximately 1 h prior to sexual activity , over a period of 28 days . Objectives : To assay the efficacy and safety of sildenafil 50 mg and placebo . Setting : Clinic- and home-based assessment s in the United Kingdom . Methods : A total of 27 subjects who were able to achieve at least a grade 2 erection ( hard , but not hard enough for penetration ) in response to penile vibratory stimulation ( PVS ) were recruited . In Part I , the reflexogenic response of the penis to PVS was evaluated in the clinic while in Part II , the response to treatment was assessed in the home ( global efficacy , question niare , diary ) . Results : In Part I , 17/26 ( 65 % ) subjects had erections of > 60 % rigidity at the penile base ( median duration 3.5 min ) after sildenafil compared with 2/26 ( 8 % ) ( median duration 0 min ) after placebo ( P=0.0003 ) . In Part II , 9/12 ( 75 % ) subjects on sildenafil and 1/14 ( 7 % ) subjects on placebo reported that the treatment had improved their erections ( P<0.005 ) , and 8/12 ( 67 % ) and 2/13 ( 15 % ) men , respectively , indicated that they wished to continue treatment ( P<0.02 ) . An analysis of diary data showed no difference between the groups with respect to the mean number of erections hard enough for penetration ( P=0.08 ) . The mean proportion of attempts at sexual intercourse that were successful was 30 and 15 % , respectively ( P=0.21 ) . Similarly , responses to the end-of-treatment question naire indicated that there were no significant differences between the groups with respect to the frequency of erections hard enough for sexual intercourse ( P=0.47 ) or that lasted as long as the subject would have liked ( P=0.11 ) . No subject discontinued sildenafil due to adverse events . Conclusion : Sildenafil is an effective , well-tolerated oral treatment for ED in SCI subjects . Sponsorship : This study was funded by Pfizer Study design : A prospect i ve study . Objectives : To investigate the risk factors predicting upper urinary tract ( UUT ) deterioration in patients with spinal cord injury ( SCI ) . Setting : Beijing , China . Methods : We review ed the medical records and UUT imaging studies of 112 patients , with a mean follow-up of 2 years . Variables evaluated for possible influence on UUTs included patient age , gender and educational background ; injury level and completeness ; bladder management method ; and the presence of adverse outcomes such as recurrent urinary tract infections and bladder stones . Video urodynamic data were also review ed . Total renal function was assessed by serum creatinine . UUT abnormalities were assessed by renal ultrasound or magnetic resonance imaging . Results : Lumbosacral spinal cord lesions likely contribute to UUT deterioration . UUT abnormalities were present in 23 patients ( 65.7 % ) in a spontaneous voiding group , 10 patients ( 20 % ) in a clean intermittent catheterization group , 15 patients ( 78.9 % ) in an indwelling urethral catheterization group and 7 patients ( 87.5 % ) in a suprapubic Foley catheterization group ( P<0.001 ) . When dividing bladder management method into two groups , catheter-free ( spontaneous and intermittent voiding ) and indwelling catheter ( urethral and suprapubic catheterization ) , there was UUT dysfunction in 33 patients ( 38.3 % ) and 22 patients ( 81.5 % ) , respectively ( P<0.001 ) . Conclusions : Lumbosacral SCI and chronic indwelling urethral and suprapubic catheterization were predictors of UUT deterioration AIM Vardenafil is a selective and highly potent phosphodiesterase type 5 ( PDE5 ) inhibitor for the treatment of erectile dysfunction ( ED ) , with improved selectivity for PDE5 and demonstrated efficacy for improving sexual function in men with ED . The current study investigated the safety and efficacy of this new PDE5 inhibitor in Japanese men with ED . METHODS This was a prospect i ve , double blind , r and omized clinical trial design ed to evaluate the efficacy and safety of vardenafil . Following a 4-week treatment-free observation period , 283 eligible patients were r and omized to 12 weeks treatment with vardenafil 5 mg , 10 mg , 20 mg , or placebo . Primary efficacy responses were assessed using the scores of Q3 and Q4 of the international index of erectile function ( IIEF ) . RESULTS All three vardenafil doses showed significantly better improvement than the placebo group in Q3 and Q4 scores of the IIEF question naire , either at 12 weeks or at the ' last observation carried forward ' ( LOCF , P < 0.0001 ) . Q3 scores were improved to 4.06 with vardenafil 5 mg , 4.53 with vardenafil 10 mg , and 4.64 with vardenafil 20 mg , versus 3.17 with placebo . Comparable scores for Q4 were 3.47 , 4.15 and 4.31 versus 2.31 for placebo . Up to 86 % of patients achieved improved erections as assessed by the global assessment question ( GAQ ) . Reported adverse event rates were 35.3 % , 45.3 % and 54.5 % with vardenafil 5 mg , 10 mg and 20 mg , respectively , versus 21.1 % in the placebo group . No serious adverse drug reactions were reported . The most common treatment-emergent adverse events were transient headache , flushing and rhinitis , which were mostly mild . CONCLUSION Vardenafil is an effective and well-tolerated treatment for ED and provides improvement in key indices of erectile function among Japanese men with ED . The results of our trial show that up to nearly 90 % of patients achieve improved erections with the administration of vardenafil Erectile dysfunction is a common complication of spinal cord injury . This double‐blind , placebo‐controlled , two‐way crossover study assessed the efficacy and safety of oral sildenafil in men with erectile dysfunction caused by traumatic spinal cord injury . A total of 178 men ( mean age , 38 years ) received placebo or sildenafil 1 hour before sexual activity for 6 weeks ; after a 2‐week washout period , the men received the alternate treatment for 6 weeks . The 50‐mg starting dose could be adjusted to 100 or 25 mg based on efficacy and tolerability . Efficacy was assessed by using global efficacy questions , the International Index of Erectile Function ( IIEF ) , and a patient log of erectile activity . Of 143 men with residual erectile function at baseline , 111 ( 78 % ) reported improved erections and preferred sildenafil to placebo . For all men ( including those who reported no residual erectile function at baseline ) , 127 of 168 ( 76 % ) reported improved erections and preferred sildenafil to placebo . For all men , 132 of 166 ( 80 % ) reported that sildenafil improved sexual intercourse compared with 17 of 166 men ( 10 % ) reporting improvement with placebo . IIEF questions assessing the ability to achieve and maintain erections and satisfaction with sexual intercourse demonstrated significant improvement with sildenafil . Sildenafil was well tolerated , with a low rate of discontinuation because of treatment‐related adverse events ( 2 % vs 1 % for placebo ) . Oral sildenafil is an effective and well‐tolerated treatment for erectile dysfunction caused by spinal cord injury . Ann Neurol & NA ; Chronic pain in persons with spinal cord injury ( SCI ) is a difficult problem for which there is no simple method of treatment . Few r and omized controlled trials of medications for pain in persons with SCI have been conducted . This study was design ed to determine whether amitriptyline , a tricyclic antidepressant , is efficacious in relieving chronic pain and improving pain‐related physical and psychosocial dysfunction in persons with SCI . Eighty‐four participants with SCI and chronic pain were r and omized to a 6‐week trial of amitriptyline or an active placebo , benztropine mesylate . All pre‐ and post‐treatment assessment s were conducted by evaluators blind to the allocation . Regression analyses were conducted to examine whether there was a medication group effect on the primary ( average pain intensity ) and secondary outcome measures . No significant differences were found between the groups in pain intensity or pain‐related disability post‐treatment , in either intent‐to‐treat analyses or analyses of study completers . These findings do not support the use of amitriptyline in the treatment of chronic pain in this population , but we can not rule out the possibility that certain subgroups may benefit Abstract Traumatic spinal cord injury ( SCI ) is associated with a lifetime of disability stemming from loss of motor , sensory , and autonomic functions ; these losses , along with increased comorbid sequelae , negatively impact health outcomes and quality of life . Early decompression surgery post-SCI can enhance patient outcomes , but does not directly facilitate neural repair and regeneration . Currently , there are no U.S. Food and Drug Administration – approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI . After an SCI , the enzyme , Rho , is activated by growth-inhibitory factors and regulates events that culminate in collapse of the neuronal growth cone , failure of axonal regeneration , and , ultimately , failure of motor and functional recovery . Inhibition of Rho activation is a potential treatment for injuries such as traumatic SCI . VX-210 , an investigational agent , inhibits Rho . When administered extradurally after decompression ( corpectomy or laminectomy ) and stabilization surgery in a phase 1/2a study , VX-210 was well tolerated . Here , we describe the design of the SPRING trial , a multicenter , phase 2b/3 , r and omized , double-blind , placebo-controlled clinical trial to evaluate the efficacy and safety of VX-210 ( NCT02669849 ) . A subset of patients with acute traumatic cervical SCI is currently being enrolled in the United States and Canada .  Medical , neurological , and functional changes are evaluated at 6 weeks and at 3 , 6 , and 12 months after VX-210 administration . Efficacy will be assessed by the primary outcome measure , change in upper extremity motor score at 6 months post-treatment , and by secondary outcomes that include question -based and task-based evaluations of functional recovery Acute traumatic spinal cord injury ( SCI ) entered the arena of prospect i ve , r and omized clinical trials almost 40 years ago , with the undertaking of the National Acute Spinal Cord Study ( NASCIS ) I trial . Since then , a number of clinical trials have been conducted in the field , spurred by the devastating physical , social , and economic consequences of acute SCI for patients , families , and society at large . Many of these have been controversial and attracted criticism . The current review provides a critical summary of select past and current clinical trials in SCI , focusing in particular on the findings of prospect i ve , r and omized controlled trials , the challenges and barriers encountered , and the valuable lessons learned that can be applied to future trials Publisher Summary This chapter explores that spinal cord injury ( SCI ) has a number of severe and disabling consequences . Although loss of function is often considered the primary issue , pain is also a major problem . In central pain conditions , small r and omized trials have shown the effectiveness of amitriptyline and lamotrigine in central post-stroke pain and of dronabinol , a cannabinoid , in pain in multiple sclerosis . It is not known whether the efficacy of drugs in other central or peripheral neuropathic pain conditions can be anticipated to have similar effects in SCI neuropathic pain . Central neuropathic pain is often considered more refractory than peripheral neuropathic pain . It has been suggested that central post-stroke pain responds better to antidepressants than SCI pain . The chapter also review s that because of the lack of sufficient data in neuropathic SCI pain , efficacy in other neuropathic pain conditions has to be considered in choosing treatment
Conclusions : This systematic review and meta- analysis indicate that PDE5 inhibitors are effective and well tolerated to treat ED secondary to SCI compared with placebo , as measured by response to GEQ , SEP2 , SEP3 and incidence of adverse events .
PDE5 inhibitors could be considered as the first choice in the treatment of ED patients with SCI
Study design : Systemic review Objective : We carried out a systematic review and meta- analysis to assess the efficacy and safety of phosphodieterase-5 ( PDE5 ) inhibitors on erectile dysfunction ( ED ) secondary to spinal cord injury ( SCI ) .