Complete Spontaneous Bowel Movements Research Articles

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study

Background and objective A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. Methods Male and female subjects (n = 135; age: 25–60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. Results CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants’ vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. Conclusion The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Efficacy and mechanism of acupuncture for functional constipation in older adults: study protocol for a randomized controlled trial.

Functional constipation (FC) is a common functional gastrointestinal disorder in clinical practice, with the prevalence of which increasing with age. With the increasing aging of the population worldwide, this problem is bound to become more prominent. Acupuncture is effective and recommended for the treatment of FC. However, little is known about how acupuncture affects the gut microbiota and inflammatory cytokines and thus improves gut function. Meanwhile, there are few high-quality clinical trials specifically focusing on acupuncture in treating FC in older people. The objective of this study is to assess the efficacy and safety of acupuncture in treating FC in older people. Additionally, the research aims to explore the mechanism of action of acupuncture in treating FC in older people by affecting intestinal microbiota and inflammation cytokines. This study is designed as a single-center, randomized, sham-controlled clinical trial. A total of 98 eligible FC patients will be randomized in a 1:1 ratio into an acupuncture group and a sham acupuncture group. Both groups will receive 24 treatments over 8 weeks with a 12-week follow-up. The primary outcome of the study is the treatment response rate, which is the proportion of participants with ≥3 mean weekly Complete Spontaneous Bowel Movements (CSBMs) over weeks 3-8. The secondary outcomes will include the proportion of participants with ≥3 mean weekly CSBMs during other assessment periods; the percentage of patients with ≥1 increase in mean weekly CSBMs from baseline; the average changes in CSBMs; Patient Assessment of Constipation-Symptoms (PAC-SYM), Bristol Stool Scale, Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and weekly usage of emergency bowel medications. Adverse events will be recorded throughout the study. Data for the outcomes will be collected at Week 0 (baseline), Week 4 (the intervention period), Week 8 (the post-treatment), Week 12 (the follow-up period) and Week 20 (the follow-up period). In addition, changes in intestinal microbiota will be analyzed using 16S rRNA high-throughput detection, and the concentration of relevant inflammatory cytokines in serum will be measured by ELISA based on blood samples. The intention-to-treat analysis will be performed in this study.Clinical trial registration: [https://www.chictr.org.cn/], identifier [ChiCTR2300070735].

Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3mg or placebo for 12weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: -1.7 vs -1.3; P = 0.002), reduced abdominal pain (-1.7 vs -1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: -1.3 vs -1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (-0.9 vs -0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

Polyethylene glycol compared to lactulose for constipation in pregnancy: A randomized controlled trial.

To compare polyethylene glycol 4000 versus lactulose in chronic constipation during pregnancy. Women at 28-32 weeks' gestation attending antenatal clinic for routine care were screened using the Rome IV chronic constipation criterion. Eligible women were approached and consented. Participants were randomized to oral polyethylene glycol (10 g/day) or lactulose (10 g/day) for 4 weeks. A bowel movement diary was kept and outcomes using the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM), Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL) and Bristol Stool Form Scale (BSFS), which were evaluated at the start and end of the four-week period. Relative risks (RR) were determined for the coprimary outcomes of complete spontaneous bowel movement (CSBM) and PAC-SYM mean score improvement (decrease in score of >1 from the baseline). A total of 4323 women underwent screening, of which 780 fulfilled the Rome IV criterion, and 360 consented to participate (180 randomized to PEG and lactulose, respectively). Data from 247 women who completed the study were analyzed. CSBM was achieved in 107/124 (86.3%) versus 102/123 (82.9%) (RR 1.04, 95% CI: 0.93-1.16, P = 0.464) for PEG and lactulose trial arms, respectively. PAC-SYM mean score improvement was 62/118 (52.5%) in the PEG arm versus 44/118 (37.3%) in the lactulose arm (RR 1.40, 95% CI: 1.05-1.88). Of secondary outcomes, a significant difference was found in favor of PEG, with respect to PAC-SYM abdominal symptoms subscale, normal stool versus loose stool consistency and side effects of vomiting and diarrhea. After controlling for parity, baseline PAC-SYM, PAC-QoL scores, characteristics different at baseline, only diarrhea and loose stools remained significant. Both PEG 4000 and lactulose are effective laxatives in pregnancy with similar performance after adjusted analysis. Diarrhea and loose stools are less frequently reported with PEG.

Placebo response to sham electroacupuncture in patients with chronic functional constipation: A secondary analysis.

Chronic severe functional constipation is a common disease that requires novel and effective treatment strategies. Acupuncture might constitute a promising therapeutic approach for chronic constipation, but it reportedly engenders an enhanced placebo response. Herein, we aimed to determine the magnitude of the placebo responses to electroacupuncture for constipation and identify its influencing factors. In this secondary analysis of a multicenter randomized trial, patients were randomized to a sham electroacupuncture group, which was administered for 8 weeks in 24 sessions of superficial needling at nonacupoints. The placebo response rates were assessed using three responder criteria: ≥3 complete spontaneous bowel movements per week (CSBMs/week), overall CSBM, and sustained CSBM. Logistic regression with backward selection method was employed to identify the potential factors that affected the placebo response. Overall, 539 patients were included in the study. The placebo response rate was 10.58%, 9.46%, and 9.09% according to the three aforementioned criteria, respectively. Those who exhibited more CSBMs/week at baseline were more likely to respond to sham electroacupuncture. Among patients with more than one CSBM per week at baseline, the response rates for achieving the criteria of ≥3 CSBMs per week, overall CSBM, and sustained CSBM were 25.40%, 30.16%, and 22.22%. Electroacupuncture did not demonstrate a large placebo response in functional constipation treatment. The number of CSBMs at baseline may be a moderator of the placebo response to sham electroacupuncture. Thus, superficial needling sham acupuncture may be considered an ideal sham control for clinical trials of chronic constipation.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

S232 Improvement in Bloating and Overall Complete Spontaneous Bowel Movement Response With Tenapanor Treatment: A Post Hoc Analysis of the IBS-C Clinical Studies

S232 Improvement in Bloating and Overall Complete Spontaneous Bowel Movement Response With Tenapanor Treatment: A Post Hoc Analysis of the IBS-C Clinical Studies

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial.

Objective: To comprehensively evaluate the effect of acupuncture on gut microbiota, identify specific microbes closely related to the clinical efficacy of acupuncture, and explored the role of short-chain fatty acids (SCFAs). Methods: A randomized placebo-controlled trial was conducted with 80 FC patients and 28 healthy controls (HCs). FC patients randomly received 16 acupuncture (n = 40) or sham acupuncture (n = 40) sessions over 4weeks; HCs received no treatment. The change in the proportion of patients with mean weekly complete spontaneous bowel movements (CSBMs) was considered as the primary outcome measure. Moreover, the composition and the predictive metabolic function of the gut microbiota from feceal samples were analyzed by 16S rRNA gene sequencing, while feceal SCFAs were identified via gas chromatography-mass spectrometry (GC-MS). Results: Compared to sham acupuncture, acupuncture significantly increased the proportion of CSBM responders, and improved spontaneous bowel movements (SBMs), straining, stool consistency, and quality of life. Moreover, Sequencing of 16S rRNA genes revealed that acupuncture improved β-diversity and restored the composition of gut microbiota. Specifically, the abundance of beneficial bacteria such as g_Lactobacillus increased while that of pathogenic bacteria such as g_Pseudomonas decreased after acupuncture, which were significantly correlated with alleviated symptoms. Moreover, ten microbes including g_Coprobacter, g_Lactobacillus, and g_Eubacterium_coprostanoligenes_group might be considered acupuncture-specific microbes, and formed a stable interaction network. Additionally, GC-MS analysis indicated that acupuncture increased the content of butyrate acid in the gut, which was positively correlated with an increase in defecation frequency and a decrease in acupuncture-related pathogens. Finally, acupuncture specific-microbes including g_Coprobacter, g_Lactobacillus, g_Pseudomonas, g_Eubacterium_coprostanoligenes_group, g_Erysipelotrichaceae_UCG.003, g_Prevotellaceae_UCG.001, and g_Rolstonia could accurately predict the clinical efficacy of acupuncture (AUC = 0.918). Conclusion: Acupuncture could effectively improve clinical symptoms in FC patients, and was associated with gut microbiota reshaping and increased butyrate acid levels. Moreover, key microbial genera such as g_Coprobacter and g_Lactobacillus was predictive of acupuncture efficacy in treating FC. Future studies are required to validate the causal relationship between key microbial genera and acupuncture clinical efficacy, and should explore further metabolic pathways for designing personalized treatment strategies. Clinical Trial Registration: http://www.chictr.org.cn, Identifier: ChiCTR2100048831.

Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study

BackgroundThe efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets.MethodsThe clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed.ResultsOverall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy.ConclusionsWMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.

Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies.

This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment. This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period. The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week. Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week. In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO.

Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials.

Patients with irritable bowel syndrome with constipation (IBS-C) experience abdominal pain with altered bowel movements. Plecanatide is indicated as IBS-C treatment in adults. This integrated analysis further characterizes plecanatide efficacy and safety in IBS-C. Data pooled from 2 identically designed phase 3 trials included adults with IBS-C randomized to plecanatide 3 mg or 6 mg, or placebo once daily for 12 weeks. A daily diary recorded stool frequency/symptoms, with abdominal pain, bloating, cramping, discomfort, fullness, and straining intensity individually rated. Overall response (primary endpoint) was defined as ≥30% improvement from baseline in average worst abdominal pain severity and increase of ≥1 complete spontaneous bowel movement, during same week (composite), for ≥6 of 12 weeks. Secondary endpoints included sustained response (overall response, plus meeting weekly composite criteria during ≥2 of last 4 treatment weeks) and changes from baseline in individual symptoms. Safety assessments included adverse event monitoring. Overall, 2176 patients (74.0% female; mean [SD] age, 43.5 [14.1] years) were included in efficacy analyses (plecanatide 3 mg [n = 724], 6 mg [n = 723], placebo [n = 729]). A significantly greater percentage of patients achieved overall response with plecanatide 3 mg (25.6%) and 6 mg (26.7%) versus placebo (16.0%; both P < 0.001 vs placebo). A significantly greater percentage of patients were sustained responders with plecanatide 3 mg (24.3%) and 6 mg (25.6%) versus placebo (15.6%; both P < 0.001 vs placebo). Significant improvements from baseline in abdominal discomfort, abdominal fullness, abdominal pain, bloating, and cramping occurred as early as Week 1 (Week 2 for abdominal pain) with plecanatide and were maintained through Week 12 versus placebo. Diarrhea, the most common adverse event, occurred in 4.3% (3 mg), 4.0% (6 mg) and 1.0% (placebo) of patients, leading to study discontinuation in 1.2%, 1.4%, and 0 patients, respectively. Plecanatide is safe and effective for treating global and individual IBS-C symptoms.

Green and gold kiwifruit powders consumed for 28 days by healthy individuals with occasional constipation are safe and well-tolerated: A randomized controlled trial

Constipation is a global issue which impacts quality of life. Therapeutic laxatives are used to rescue constipation, but they may have side effects such as urgency, gas, bloating or gastrointestinal discomfort. Kiwifruit are thought to promote laxation without the urgency induced by therapeutic laxatives. The objective of this study was to examine the safety and tolerability of a 2,400 mg daily dosage of green kiwifruit powder or gold kiwifruit powder, a 600 mg of green kiwifruit powder or gold kiwifruit powder combined with cellulose, and a combination of 600 mg green kiwifruit powder plus 1,400 mg xylo-oligosaccharide. This randomised, double-blinded, placebo-controlled, parallel study for 28 days across four North American sites (NCT03462199) enrolled 288 participants with non-pathological constipation who had ≤3 complete spontaneous bowel movements (CSBM) per week. Baseline demographics, anthropomorphic and vital signs, clinical chemistry and hematology, and patient assessment of quality-of-life questionnaire, and adverse events data were collected at baseline and end of intervention. All investigational products had no clinically relevant changes to blood chemistry or hematology, and no adverse events linked to the investigational products. However, there were significant (p < 0.05) within-group improvements in patient-assessed quality of life scores in physical discomfort, psychosocial discomfort, worries/concerns, and satisfaction, and overall PAC-QoL scores for all products and placebo. These kiwifruit-derived products were safe and well-tolerated.

The Effect of Electrolyzed Hydrogen-Rich Alkaline Reduced Water on Patients with Chronic Constipation—A Clinical Trial

Chronic constipation is a common symptom-based disorder that affects patient quality of life. Electrolyzed hydrogen-rich alkaline reduced water (EHARW) helps treat gastrointestinal disorders owing to its various bioactive properties. This single-arm, open-labelled study aimed to investigate the improvement of EHARW (pH 9.5; H2 ≈ 0.5 mg/L) in chronic constipation patients. Thirty patients with chronic constipation were enrolled after screening as intention-to-treat (ITT). During the intervention period, two patients dropped out, and 28 patients completed the study as per protocol (PP). The selected patients were instructed to drink EHARW (pH 9.5; H2 ≈ 0.5 mg/L) (20 mL/kg body weight/day) generated from a home medical device for four weeks. Complete spontaneous bowel movement (CSBM) frequency was measured as the primary outcome, and Bristol stool form, patient assessment of constipation–symptoms (PAC-SYM) score, and patient assessment of constipation–quality of life (PAC-QOL) score were measured as the secondary outcomes after the 4-week intervention compared to baseline. As a result of EHARW treatment, no adverse events were observed during the study period. Moreover, the frequency of CSBM/week (29.8%, p &lt; 0.05) and Bristol stool form score (24.6%, p &lt; 0.01) significantly increased compared to baseline. Finally, the overall and subscale scores of the PAC-SYM (58.0%) and PAC-QOL (54.2%) questionnaires significantly decreased (p &lt; 0.001). These results suggest that daily ingestion of EHARW (pH 9.5; H2 ≈ 0.5 mg/L) can improve CSBM frequency as a primary outcome in chronic constipation patients. Likewise, EHARW (pH 9.5; H2 ≈ 0.5 mg/L) improved Bristol stool form score, symptoms and the quality of life as a secondary outcome in patients with chronic constipation through a home-based intervention.

Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.

Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.

Efficacy of a prebiotic formulation for treatment of functional constipation and associated gastrointestinal symptoms in adults: A randomised controlled trial

ObjectivesFunctional constipation is the result of a complex interplay between the gastrointestinal tract, the gut microbiome, the nervous system, along with diet and lifestyle factors. This study aimed to evaluate the efficacy of a prebiotic formulation containing plant-based extracts rich in dietary fibre and polyphenols in the management of functional constipation and associated gastrointestinal symptoms. DesignThis 3-week randomised controlled study assessed the effect of a prebiotic formulation (6 g powder taken in water twice daily), by comparison with a capsule designed to have minimal effect on gastrointestinal function, on indicators of bowel health in healthy adults with low fibre intake and meeting the Rome IV criteria for functional constipation. MethodsParticipants were informed that they may receive one of two products, either a powder or a capsule, both of which contained prebiotics. The primary outcome was change in frequency of complete spontaneous bowel movements. Secondary outcomes assessed were gastrointestinal symptoms, quality of life and mood using the PAC-SYM, PAC-QoL, and DASS-21. Safety and tolerability were also assessed. ResultsThere was a significant improvement in bowel movements (p < 0.001) and improved stool consistency (p < 0.01) in participants taking the prebiotic powder formulation compared to those taking the capsule. Accompanying this was a significant reduction in overall gastrointestinal symptoms (p < 0.001) including abdominal (p < 0.001), rectal (p = 0.004) and stool (p = 0.002) symptoms, and a significant improvement in quality of life (p 0.001). There was a significant reduction in mean score for depression, anxiety, and stress for participants in both groups, which indicated a significant improvement in mood during the study that was unrelated to bowel function. ConclusionsThe results showed that the prebiotic powder formulation taken twice per day for 21 days was effective in reducing clinical symptoms of functional constipation in individuals reporting a low fibre intake.

Interferential therapy for chronic constipation in adults: The CON‐COUR randomizedcontrolled trial

Background Chronic constipation (CC) is a frequent condition, and the first-line treatment includes dietary rules, the use of laxatives, and biofeedback for evacuation disorders. However, almost half of the patients are dissatisfied with their current treatment. We report the first double-blind randomized multicenter trial assessing the effectiveness of transabdominal electrical stimulation by interferential therapy (IFT) in the treatment of CC in adults. Methods A prospective, multicenter, randomized, double-blind, sham-controlled, parallel-group, phase 3 trial was conducted at 7 centers in France. The primary endpoint was 8-week efficacy as defined by the number of complete spontaneous bowel movements during the last 4 weeks of the 8-week stimulation period. Secondary endpoints included the evaluation of the effects of IFT on symptoms (Patient Assessment of Constipation Symptoms questionnair (PAC-SYM)), quality of life (QOL) (Patient Assessment of Constipation Quality of Life), Colonic transit time (CTT), anorectal manometry, and patient satisfaction. Results The proportion of 8-week responders was not significantly different between the two groups (73.2% in the IFT group vs. 67.1% in the sham group). After 8 weeks of stimulation, the mean overall PAC-SYM score and the mean reduction in the overall PAC-SYM score were significantly greater in the IFT group than in the sham group. No differences were observed concerning CTT, anorectal manometry, or patient satisfaction. Conclusions Although the primary endpoint was not reached, IFT can significantly alleviate the symptoms and improve the QOL of CC patients. It can be assumed that new treatments require different modes of evaluation and that the assessment of patient-reported outcomes may become a priority among therapeutic targets of CC. Trial registration number NCT02381665.

Effects of treatment cessation and re-treatment in randomized controlled trials of prucalopride in patients with chronic idiopathic constipation.

Prucalopride is a selective, high-affinity serotonin type 4 receptor agonist approved for the treatment of chronic idiopathic constipation (CIC) in adults. We investigated the impact of prucalopride cessation and re-treatment on efficacy and safety. Data were from two randomized controlled trials in adults with CIC. In a dose-finding trial, complete spontaneous bowel movements (CSBMs) and treatment-emergent adverse events (TEAEs) were assessed during a 4-week run-out period after a 4-week treatment period (TP; prucalopride 0.5-4 mg once daily or placebo). In a re-treatment trial, CSBMs and TEAEs were assessed during two 4-week TPs (prucalopride 4 mg once daily or placebo) separated by a 2- or 4-week washout period. In the dose-finding trial (N=234; 43-48 patients/group), mean CSBMs/week and the proportion of responders (≥3 CSBMs/week) were higher with prucalopride than placebo during the TP, but similar in all groups 1-4 weeks after treatment cessation. TEAEs were less frequent following treatment cessation. In the re-treatment trial (efficacy analyses: prucalopride, n=189; placebo, n=205), the proportion of responders was similar in both TPs and significantly higher (p ≤ 0.001) with prucalopride (TP1, 38.6%; TP2, 36.0%) than placebo (TP1, 10.7%; TP2, 11.2%). Most patients who responded to prucalopride in TP1 responded again in TP2 (71.2%). TEAEs were less frequent in TP2 than TP1. Prucalopride cessation resulted in a loss of clinical effect to baseline levels within 7 days. Similar efficacy and safety were observed between TP1 and TP2 after prucalopride was re-initiated following a washout period.

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients’ quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects’ gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.

The effect of spinal magnetic stimulation on the management of functional constipation in adults

BackgroundFunctional constipation is a type of functional bowel disorder characterized by difficult defecation with a sense of incomplete evacuation. It is a common disorder with an increasing prevalence, and the underlying cause is poorly identified. Nonpharmacological management of functional constipation includes lifestyle and dietary modification, regular physical activity, advice about toileting posture, and behavioral therapy. Biofeedback training as part of the behavioral training showed great efficacy with long-term results. Spinal magnetic stimulation is the application of extracorporeal magnetic stimuli to the spinal nerves and deep pelvic muscles to enhance bowel evacuation without surgical drawbacks. This study was designed to enhance bowel elimination in functional constipation patients through the dual effect of biofeedback and spinal magnetic stimulation. This work aimed to study the efficacy of spinal magnetic stimulation and biofeedback training versus biofeedback alone in the management of functional constipation.ResultsThere was a statistically significant difference between before and after the intervention in both studied groups regarding the mean weekly spontaneous bowel movement, a Numerical Rating Scale for pain assessment, and the Patient Assessment of Constipation Quality of Life questionnaire. When comparing the two groups after the intervention, the spinal magnetic stimulation showed superiority in the mean weekly spontaneous bowel movement and manometric anal pressure at rest.ConclusionsSpinal magnetic stimulation in addition to biofeedback pelvic floor muscle training could increase the mean weekly complete spontaneous bowel movements and manometric anal pressure at rest in patients with functional constipation. It did not show any additive benefits in improving pain during defecation or patient quality of life.Trial registrationClinicalTrials.gov, 0305398. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BQ0H&selectaction=Edit&uid=U0004JW0&ts=2&cx=-xmnims

Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation

Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation. We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed. Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P= .001 for CSBM1; 22.7% vs 11.4% P= .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial. In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239).