Constipation In Adults Research Articles

A Phase I Study to Investigate the Absorption, Pharmacokinetics, and Excretion of [14C]Prucalopride After a Single Oral Dose in Healthy Volunteers

PurposeChronic constipation is a prevalent gastrointestinal disorder globally. It is often treated with medications such as laxatives. Newer therapies to improve gastric motility include the selective 5-hydroxytryptamine receptor-4 agonist prucalopride, which is licensed for the treatment of chronic constipation in adults. The aim of this study was to investigate the pharmacokinetic properties and excretion of prucalopride in healthy individuals, using a microtracer approach with 14C radioactivity detection using liquid scintillation counting and accelerator mass spectrometry. MethodsThis was a single-period, open-label, nonrandomized absorption, metabolism, and excretion study of [14C]prucalopride. Participants were 6 healthy men aged 18 to 50 years. After screening, participants were administered a single dose of [14C]prucalopride succinate 2 mg (~200 nCi). Postadministration, urine, feces, and blood samples were collected over a 10-day period. Safety and adverse event data were also collected. FindingsAlmost 100% of the administered dose of radioactivity was recovered, with a mean (SD) of 84.2% (8.88%) recovered in urine and 13.3% (1.73%) recovered in feces. The mean blood-to-plasma concentration ratio of 1.9 indicated uptake of prucalopride into blood cells. The renal clearance of prucalopride was 17.0 (2.5) L/h, which is higher than the glomerular filtration rate in healthy individuals, suggesting active renal transport of prucalopride. Prucalopride was well tolerated, with no serious adverse events reported. ImplicationsPrucalopride was well absorbed and excreted mainly by the kidneys, including both passive and active transporter mechanisms. Quantitative recovery of the radioactive dose was achieved. Consistent with previous studies, prucalopride was generally well tolerated. ClinicalTrials.gov identifier: NCT01807000.

Patient considerations in the management of chronic constipation: focus on prucalopride.

Chronic constipation is a common condition that significantly impacts health care utilization, productivity, and quality of life. Laxatives are commonly used, although often insufficient in restoring normal bowel function or providing adequate relief. There remains a significant need for the development of novel agents to optimize treatment of this condition. This review provides an overview of the preclinical and clinical trial data, supporting the efficacy and safety of prucalopride, a highly selective 5-HT4 receptor agonist that has been approved by the European Medicine Agency for the treatment of chronic constipation in adults who have failed standard laxative therapy. Unlike older 5-HT4 agonists, prucalopride has not been associated with adverse cardiovascular side effects or QT prolongation owing to its high selectivity and affinity for the 5-HT4 receptor without clinically significant cross-reactivity at the human ether-à-go-go-related gene (hERG) potassium channel or 5-HT receptor subtypes that have previously been implicated in adverse cardiovascular events and arrhythmias. Careful safety assessments have documented the relative safety and tolerability of this agent in various patient groups. Focus has also been placed on demonstrating efficacy with regard to bowel function, symptoms, and patient-reported outcomes such as the Patient Assessment of Constipation-Symptoms and the Patient Assessment of Constipation Quality of Life scores to support the use of prucalopride as a safe and effective therapeutic option for the management of chronic constipation.

Managing constipation in adults with co-morbidities

Methods of identifying the causes and treatments, are discussed by Angela Gardiner and Andrea Hilton

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis.

Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required.

Systematic review with meta-analysis: effect of fibre supplementation on chronic idiopathic constipation in adults.

Chronic idiopathic constipation is a common symptom-based gastrointestinal disorder responsible for a substantial economic health service burden. Current guidelines recommend the use of fibre as a first-line treatment. To investigate the effect of fibre (including prebiotic) supplementation on global symptom response, stool output, gut microbiota composition and adverse events in adults with chronic idiopathic constipation. Medline, EmBase, Web of Science, Scopus and the Cochrane central register of controlled trials were searched through to February 2016. Conference proceedings from 2003 to 2015 were hand-searched. There were no language restrictions. Forest plots with 95% CIs were generated using a random-effects model. The search strategy generated 1072 citations, of which seven individual randomised controlled trials were eligible. Overall, 113 of 147 (77%) patients assigned to fibre responded to therapy, compared with 61 of 140 (44%) allocated to placebo (RR of success to respond 1.71, 95% CI 1.20-2.42, P = 0.003). Fibre significantly increased stool frequency (SMD, standardised mean difference = 0.39; 95% CI 0.03-0.76; P = 0.03) and softened stool consistency (SMD = 0.35; 95% CI 0.04-0.65; P = 0.02) compared with placebo. Flatulence was significantly higher with fibre compared to placebo (SMD 0.56, 0.12-1.00, P = 0.01). Overall quality of evidence was low. This meta-analysis demonstrates that fibre is moderately effective, but also causes moderate gastrointestinal side effects. However, these findings need to be treated with caution due to a high risk of bias. Accordingly, further large, methodologically rigorous trials are required, before any definitive recommendation regarding its risk-benefit profile can be made. PROSPERO registration number CRD42014007005.

Prucalopride: For functional constipation only?

Prucalopride is a new prokinetic agent, recently available in Europe for the treatment of functional constipation in adults in whom treatment with laxatives failed to provide adequate relief. However, due to its intrinsic properties (highly selective agonist activity and high affinity for 5-HT4 receptors, neuroprotection), this drug has shown the potential to be used in other pathologic conditions, in and outside of the gastrointestinal tract. We performed a systematic review of the evidence supporting these possible alternative uses of prucalopride. Further studies in this area are, however, mandatory.

Diagnosis and management of chronic constipation in adults.

Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurological or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction. This subtype of constipation can be identified using either the radio-opaque marker test or wireless motility capsule test, and is best treated with laxatives such as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If unsuccessful, subspecialist referral should be considered. Dyssynergic defecation results from impaired coordination of rectoanal and pelvic floor muscles, and causes difficulty with defecation. The condition can be identified using anorectal manometry and balloon expulsion tests and is best managed with biofeedback therapy. Opioid-induced constipation is an emerging entity, and several drugs including naloxegol, methylnaltrexone and lubiprostone are approved for its treatment. In this Review, we provide an overview of the burden and pathophysiology of chronic constipation, as well as a detailed discussion of the available diagnostic tools and treatment options.

Normative values for stool frequency and form using Rome III diagnostic criteria for functional constipation in adults: systematic review with meta-analysis.

When designing clinical trials focused on functional constipation therapies, understanding the normative values of populations selected using the Rome III criteria is important for estimating baseline symptom severity, and for power analysis and sample size calculations. The objective of this review was to determine normative ranges for stool frequency and form in adults with functional constipation (Rome III criteria). Eligible studies reported stool frequency or form; random effects meta-analysis was performed with subgroup analyses to explore sources of heterogeneity. A total of 25 studies (43 groups, 2292 subjects) were included. Pooled estimates were 2.7 (95% CI 2.4-3.0) for weekly stools and 2.4 (95% CI 2.1-2.6) for stool form (Bristol scale). Heterogeneity was high for both outcomes (both I2=96%, P<0.001). Subgroup analysis revealed that weekly bowel movement frequency was higher in larger than in smaller studies (3.1 vs. 2.3, P<0.001) and in studies conducted in Europe compared with those in the Americas (3.1 vs. 2.2, P=0.02). For stool form, the use of a daily diary versus subject recall was the sole explanatory variable (2.5 vs. 2.1, P<0.05). We conclude that adults with functional constipation have significant variation in stool frequency and form, explained in part by geography and study design.

Outcome of a public consultation on the draft guidance of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms

Outcome of a public consultation on the draft guidance of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms

▼Naloxegol for opioid-induced constipation

▼Naloxegol (Moventig—AstraZeneca) is a peripherally acting mu-opioid receptor antagonist licensed for the treatment of opioid-induced constipation in adults who have had an inadequate response to laxative treatment.1 It was launched...

Randomized Double-blind Controlled Trial: Benefits of Lactobacillus reuteri in Chronic Functional Constipation Patients

Background: Chronic functional constipation is a common problem that affects between 15-25% of the population and cause symptoms and disorders that creates discomfort, morbidity, and high costs for health care. Recently, the consumption of probiotics in treating chronic constipation in adults have been investigated. However, there are still limited and controversial evidences available from controlled trials. The aim of this study was to evaluate the effects of Lactobacillus reuteri (L. reuteri) in improving the Agachan constipation score, the number of L. reuteri in the feces and the fecal pH in the patients with chronic functional constipation.Method: A double-blind, placebo randomized controlled trial (RCT) was conducted in 40 adults (12 males/28 females with mean age 45.95 ± 16 years) affected by chronic functional constipation according to Rome III criteria. Patients were randomly assigned to receive a supplementation of L. reuteri or placebo for 4 weeks.Results: At week 4, the decrease in Agachan constipation score was from 17.00 to 8.00 with p 0.001, the increase number of L. reuteri was from 6.80 x 107 to 2.12 x 108 with p 0.001 and the decrease of pH feces was from 5.44 (SD 0.70) to 4.78 (SD 0.56) with p 0.001 in the L. reuteri group, otherwise in the placebo group there were no significant results in Agachan constipation score, the number of L. reuteri and fecal pH assessed.Conclusion: L. reuteri is more effective than the placebo group in improving the Agachan constipation score, increasing the number of L. reuteri in the feces and decreasing the fecal pH in adult with chronic functional constipation.

Use of Antegrade Continence Enema for the Treatment of Fecal Incontinence and Functional Constipation in Adults: A Systematic Review.

Antegrade continence enema is a proximal colonic stoma that allows antegrade lavage of the colon for the treatment of fecal incontinence and functional constipation. Its role in the treatment of these conditions in adults has not been established. This review aimed to evaluate the clinical response and complications of antegrade continence enema in the adult population. A systematic literature search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from January 1980 to October 2013 was conducted. Studies reporting clinical outcomes of antegrade continence enema in adult patients were considered. Only studies with participants aged 16 years and older were selected. Use of the antegrade continence enema for the treatment of constipation and incontinence in adults was investigated. The primary outcome was the number of patients irrigating their stoma. Secondary outcomes included the incidence of stoma stenosis, assessment of functional outcome, and evaluation of quality of life. Overall, 15 studies were selected, describing outcomes in 374 patients. All of the reports were observational cross-sectional studies, and 4 were prospective. The number of participants still using their stoma ranged from 47% to 100% over a follow-up period of 6 to 55 months. Eleven studies reported achievement of full continence in 33% to 100% of patients. Four studies described functional outcomes, and 7 studies reported a wide range of patient satisfaction. The rate of stoma stenosis varied from 8% to 50%. There were considerable heterogeneities within and across studies. Most studies were of poor quality, as reflected in the Methodological Index for Nonrandomized Studies score. Antegrade continence enema has been reported as an acceptable treatment of both functional constipation and fecal incontinence in adults across several analyses. There is wide variation regarding outcome measures. Larger prospective studies are required to assess the role of antegrade continence enema in the adult population.

Approaches to managing chronic constipation in older people within the community setting.

Constipation is a common presenting problem within the community setting, but its treatment is often unsatisfactory. It is important for nurses to remember that constipation is a symptom and not a disease. For older adults, constipation can have a gradual onset over a number of years, with many people 'self-medicating' with over-the-counter laxatives and herbal products, which then result in the need for daily laxatives. This article will consider best practice for the assessment, treatment, and prevention of constipation in adults within the community.

Sacral nerve stimulation for faecal incontinence and constipation in adults.

Sacral nerve stimulation for faecal incontinence and constipation in adults.

Prevalence of self-reported constipation in adults from the general population

To estimate the prevalence of self-reported constipation and associated factors in the general population of a Brazilian city. Secondary analysis of an epidemiological study, population-based, cross-sectional study, about bowel habits of Brazilian population. A total of 2,162 individuals were interviewed using two instruments: sociodemographic data and the adapted and validated Brazilian version of the "Bowel Function in the Community" tool. There was a prevalence of 25.2% for the self-reported constipation, 37.2% among women and 10.2% among men. Stroke and old age were associated with constipation in the three statistical models used. The prevalence found showed to be similar to the findings in the literature, although some associated factors obtained here have never been investigated.

PTU-219 Use of antegrade colonic enema for the treatment of faecal incontinence and functional constipation in adults: a systematic review

Introduction Antegrade continence enema (ACE) is a proximal colonic stoma that allows antegrade lavage of the colon for the treatment of faecal incontinence (FI) and functional constipation (FC). Since its first description, 1 it has become widely accepted in the paediatric population. However, its role in the treatment of these conditions in adults has not been established. This review aims to evaluate the clinical response and complications of ACE in the adult population. Method The Medline and EMBASE databases were searched using the following criteria: (antegrade AND (continent OR continence OR colonic) AND enema).ti, ab [Limit to: Humans and (Age Groups All Adult 19 plus years)]. The Cochrane Central Register of Controlled trials (CENTRAL) was searched using the term “antegrade continence enema” in the Title, Abstract or Keywords section. Two independent reviewers screened abstracts and selected studies for inclusion. Only studies with participants aged 16 years and above were selected and quality of study was assessed using the MINORS score. 2 Results In all, 381 articles were retrieved, of which, 90 were duplicates. After review of the 291 abstracts, 32 full text publications were scrutinised and 18 were found to meet the inclusion criteria. Four studies were from the same institution, hence, 15 studies describing outcomes in 384 patients were included in the final analysis. All reports were observational cross sectional studies, four were prospective. Six studies included patients with either FC or FI, four with FI alone and five with FC alone. There was considerable heterogeneity within and across studies, hence, meta-analysis was not possible. Most studies were of poor quality as reflected in the low MINORS score. The number of participants still using ACE ranged from 47% to 100% over a follow up period of 6 to 55 months. Eleven studies reported achievement of full continence in 33% to 100% patients. Four studies described functional outcomes and seven studies reported a wide range of patient satisfaction. The rate of stoma stenosis varied from 8% to 50% and the rate of end stoma varied from 0–24%. Conclusion ACE has been reported as an acceptable treatment of FI or FC in adults across several analyses. There is wide variation regarding outcome measures. Larger prospective studies are required to assess the role of ACE in the adult population. Disclosure of interest None Declared. References Malone PS, Ransley PG, Kiely EM. Preliminary report: the antegrade continence enema. Lancet 1990;336:1217–8 Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73:712–6

CON-COUR study: Interferential therapy in the treatment of chronic constipation in adults: study protocol for a randomized controlled trial.

BackgroundThe prevalence of chronic constipation is about 15 % in Western countries with a significant impact on quality of life and health care costs. The first-line therapy, based on medical treatment combined with laxatives and dietary rules, is often disappointing. Interferential therapy is a new treatment that has demonstrated its efficiency in the treatment of chronic constipation in children and encouraging results in adults. The primary objective of this study is to assess the efficacy of interferential therapy during 8 weeks in adult patients. The secondary objectives are to assess this new and noninvasive therapy in terms of persistence of the clinical efficacy, colonic transit time, ano-rectal manometry, patient satisfaction and quality of life (QoL), and tolerance.Methods/DesignDesign: multicenter, prospective, randomized, placebo-controlled, double blind, two-parallel groups study. Setting: nine French adult gastroenterology centers. Inclusion criteria: adult patients with a history of chronic constipation refractory to medical treatment for at least 3 months. Treatment groups: (1) interferential-experimental group (effective stimulation); (2) placebo-control group (sham stimulation). Randomization: 1:1 allocation ratio. Evaluation times: inclusion (T0, randomization), baseline assessment (T1), start of stimulation (T2), intermediary assessment (T3, 4 weeks), end of stimulation (T4, 8 weeks), follow-up (T5 and T6, 1- and 6-month). Endpoints: (1) primary: short-term efficacy at T4 (treatment response defined as three or more spontaneous, complete bowel movements per week); (2) secondary: efficacy at T5 and T6, symptoms (Patient Assessment of Constipation Symptoms questionnaire), colonic transit time, anorectal manometry, patient satisfaction (analogical visual scale), patient QoL (Patient Assessment of Constipation Quality of Life Questionnaire), side/unexpected effects. Sample size: 200 individuals to obtain 80 % power to detect a 20 % difference in treatment response at T4 between the two groups (15 % of lost to follow-up patients expected).DiscussionThe randomized, double-blind, placebo-controlled design is the most appropriate to demonstrate the efficacy of a new experimental therapeutic (Evidence-Based Medicine Working Group classification). National and international recommendations could be updated based on the findings of this study.Trial registrationCurrent controlled trials NCT02381665 (registration date: February 13, 2015).

Prevention and management of constipation in adults.

Constipation is a common, often chronic, condition that is a health concern for providers of care. The condition can be distressing and although seldom life-threatening can lead to patient discomfort and debilitating effects on patients' quality of life. Initial management of chronic constipation should include lifestyle changes and increased fibre and fluids. More active interventions include the use of laxatives and other medications, irrigation and biofeedback therapy. Some patients may require surgery. This article provides an overview of the strategies used to prevent constipation in adults as well as the possible treatment options available.

The Effect of Fibre on Chronic Constipation in Adults: A Systematic Review

The Effect of Fibre on Chronic Constipation in Adults: A Systematic Review

Clinical benefits after soluble dietary fiber supplementation: a randomized clinical trial in adults with slow-transit constipation

To explore the effect of pectin, a kind of soluble dietary fiber, on colonic transit time (CTT), clinical symptoms and gut microbiota in adults with slow-transit constipation. A total of 80 patients with slow-transit constipation were selected between June 2011 and December 2013. For this randomized controlled trial, we evaluated the efficacy of pectin on intestinal transit time and other indices of constipation in adults with slow-transit constipation. They were randomized to receive either pectin or placebo. Treatment consisted of 4-week supplementation with 24 g/d pectin (fiber group) or maltodextrin (placebo group). Before and after 4-week treatment, CTT, constipation symptoms and fecal bacterial population were compared between groups. CTT of the fiber group after treatment was lower than those of fiber group before treatment and those in the placebo group ((60.2 ± 11.2) h vs (80.3 ± 9.5), (79.4 ± 11.7) h, P < 0.01). Constipation score of the fiber group after treatment also decreased than those of fiber group before treatment and those in the placebo group (both P < 0.05). Bifidobacterium sp. and Lactobacillus sp. evidently increased (lg copies/g:8.26 ± 0.83 vs 6.42 ± 1.07 and 6.48 ± 0.82, 6.83 ± 0.77 vs 5.85 ± 0.64 and 5.91 ± 0.73; all P < 0.05) and total Clostridium sp. significantly decreased (9.07 ± 0.63 vs 9.74 ± 0.81 and 9.66 ± 0.43, P < 0.05) in the fiber group after treatment versus the placebo group. No significant adverse effects were reported. Four-week soluble dietary fiber use accelerates colon transit time and alleviates clinical symptoms in patients with slow-transit constipation. Additionally, supplementary fiber offers protective effects on gut microbiota by increasing the population of healthy microflora.