Dataset Information

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

ABSTRACT: Pilot data of our phase IV clinical trial (pre/post study design) highlighted a beneficial effect of intradetrusor onabotulinumtoxinA (200 IU) injections to reduce autonomic dysreflexia (AD) in individuals with chronic spinal cord injury (SCI) at T6 or above. After trial completion, we assessed whether our primary expectation (i.e., decrease of AD severity in 50% of participants during urodynamics [UDS]) was met. Secondary outcome measures were reduction of spontaneous AD in daily life as well as amelioration of AD-related and urinary incontinence-related quality of life (QoL). In addition, we conducted injury-level-dependent analysis-i.e., cervical and upper thoracic-to explore group-specific treatment efficacy. Post-treatment, AD severity decreased in 82% (28/34) of all participants during UDS and in 74% (25/34) in daily life assessed with 24-h ambulatory blood pressure monitoring. In addition, urinary incontinence-related QoL was improved, cystometric capacity was increased, and maximum detrusor pressure during storage was reduced (all p?

SUBMITTER: Walter M

PROVIDER: S-EPMC7470218 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

Walter Matthias M Kran Stephanie L SL Ramirez Andrea L AL Rapoport Daniel D Nigro Mark K MK Stothers Lynn L Kavanagh Alex A Krassioukov Andrei V AV

Journal of neurotrauma 20200723 18

Pilot data of our phase IV clinical trial (pre/post study design) highlighted a beneficial effect of intradetrusor onabotulinumtoxinA (200 IU) injections to reduce autonomic dysreflexia (AD) in individuals with chronic spinal cord injury (SCI) at T6 or above. After trial completion, we assessed whether our primary expectation (i.e., decrease of AD severity in 50% of participants during urodynamics [UDS]) was met. Secondary outcome measures were reduction of spontaneous AD in daily life as well a ...[more]

PMID: 32631152

Similar Datasets

Project description:BackgroundAnticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed.MethodsWe performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events.ResultsOf 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001).ConclusionsOral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).

Project description:BACKGROUND:Women with refractory urgency urinary incontinence can be treated with onabotulinumtoxinA or sacral neuromodulation. Little data exists on the comparative effects of treatment of refractory urgency urinary incontinence on other pelvic floor complaints, such as bowel and sexual function. OBJECTIVE:The objective of this study was to compare the impact of these treatments on fecal incontinence and sexual symptoms. METHODS:This was a planned supplemental analysis of a randomized trial in women with refractory urgency urinary incontinence treated with onabotulinumtoxinA (n = 190) or sacral neuromodulation (n = 174). Fecal incontinence and sexual symptoms were assessed at baseline and at 6, 12, and 24 months. Fecal incontinence symptoms were measured using the St Mark's (Vaizey) Fecal Incontinence severity scale. Sexual symptoms were measured using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) and the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). The PISQ-IR allows measurement of sexual symptoms in both sexually active and non-sexually active adults. Primary outcomes were change in Vaizey and PISQ-12 scores between baseline and 6 months. Secondary outcomes were change in PISQ-IR total and subscores between baseline and 6 months and change in Vaizey, PISQ-12, and PISQ-IR scores between baseline and 12 and 24 months. Intent-to-treat analysis was performed using repeated measures mixed model to estimate change in all parameters from baseline while adjusting for the baseline score. A subgroup analysis of women with clinically significant bowel symptoms was conducted based on baseline Vaizey score of ?12. RESULTS:At baseline, mean Vaizey scores were indicative of mild fecal incontinence symptoms and were not different between onabotulinumtoxinA and sacral neuromodulation groups (7.6 ± 5.3 vs 6.6 ± 4.9, P = .07). The proportion of sexually active women (56% vs 63%, P = .25), mean PISQ-12 score (33.4 ± 7.5 vs 32.7 ± 6.7, P = .55), or PISQ-IR subscores were also not different between the onabotulinumtoxinA and sacral neuromodulation groups at baseline. There was no difference between women treated with onabotulinumtoxinA and those treated with sacral neuromodulation at 6 months in terms of improvement in fecal incontinence symptom score (Vaizey: -1.9, 95% confidence interval -2.6 to -1.2 vs -0.9, 95% confidence interval -1.7 to -0.2, P = .07) or sexual symptoms score (PISQ-12: 2.2, 95% confidence interval 0.7 to 3.7 vs 2.2, 95% confidence interval 0.7 to 3.7, P = .99). There was no difference in improvement between groups in the sexual symptom subscores in sexually active and non-sexually active women at 6 months. Similar findings were noted at 12 and 24 months. In a subgroup (onabotulinumtoxinA = 33 and sacral neuromodulation = 22) with clinically significant fecal incontinence at baseline (Vaizey score ?12), there was a clinically meaningful improvement in symptoms in both groups from baseline to 6 months, with no difference in improvement between the onabotulinumtoxinA and sacral neuromodulation groups (-5.1, 95% confidence interval -7.3 to -2.8 vs -5.6, 95% confidence interval -8.5 to -2.6, P = .8). CONCLUSION:There were no differences in improvement of fecal incontinence and sexual symptoms in women with urgency urinary incontinence treated with onabotulinumtoxinA or sacral neuromodulation. Women with significant fecal incontinence symptoms at baseline had clinically important improvement in symptoms, with no difference between the treatments. Our findings can help clinicians counseling women considering treatment for refractory urgency urinary incontinence.

Project description:BackgroundThe control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood.Methods/designThis is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis.DiscussionThis study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control.Trial registrationClinicalTrials.gov NCT01768910.

Project description:PURPOSE:We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes. MATERIALS AND METHODS:First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ?0.01 and p ?0.004 represented moderate evidence of an association with outcomes. RESULTS:Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother. CONCLUSIONS:Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.

Dataset Information

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

Publications

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure