A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit. Antagonism at the 5-HT3 receptor may be of benefit in the treatment of irritable bowel syndrome. AIMS: To evaluate the effect of 12 weeks of treatment with alosetron, a 5-HT3 receptor antagonist at doses of 0.1 mg b.d., 0.5 mg b.d. and 2 mg b.d. in irritable bowel syndrome patients. METHODS: A double-blind, placebo-controlled, parallel-group study with a 2-week screening and a 12-week treatment period was conducted. A total of 462 patients (335 female) recorded details of the severity of their abdominal pain, and bowel function daily on a diary card throughout the study. At monthly clinic visits patients recorded the severity of their abdominal pain/discomfort and diarrhoea on a visual analogue scale. RESULTS: In the total population and in the female subpopulation (but not in males) alosetron 2 mg b.d. significantly increased the proportion of pain-free days and decreased the visual analogue scale score for diarrhoea compared with placebo. Alosetron at doses of 0.5 mg b.d. and 2 mg b.d. led to a significant hardening of stool, and a reduction in stool frequency in the total population. CONCLUSION: Alosetron at a dose of 2 mg b.d. is an effective treatment for female patients with irritable bowel syndrome.     

Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study

Aim:

To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria.

Methods:

Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored.

Results:

The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0% vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups, but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators’ global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01).

Conclusions:

Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/discomfort) more than placebo does.

     

A randomized,double-blind,placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation

BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.     

Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study

BACKGROUND: Melatonin is involved in the regulation of gastrointestinal motility and sensation. AIM : To determine the potential therapeutic effects of melatonin in irritable bowel syndrome (IBS). METHOD: Seventeen female patients satisfying the Rome II criteria for IBS were randomized to receive either melatonin 3 mg nocte or identically appearing placebo 1 nocte for 8 weeks, followed by a 4-week washout period and placebo or melatonin in the reverse order for another 8 weeks. Three validated questionnaires - the GI symptom, the sleep questionnaires and the Hospital Anxiety and Depression Scale - were used to assess symptom severity and to compute the IBS, sleep and anxiety/depression scores, respectively. RESULTS: Improvements in mean IBS scores were significantly greater after treatment with melatonin (3.9 +/- 2.6) than with placebo (1.3 +/- 4.0, P = 0.037). Percent response rate, defined as percentage of subjects achieving mild-to-excellent improvement in IBS symptoms, was also greater in the melatonin-treated arm (88% vs. 47%, P = 0.04). The changes in mean sleep, anxiety, and depression scores were similar with either melatonin or placebo treatment. CONCLUSIONS: Melatonin is a promising therapeutic agent for IBS. Its therapeutic effect is independent of its effects on sleep, anxiety or depression.     

Randomized,double-blind,placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome

BACKGROUND: Post-infectious irritable bowel syndrome is associated with increased serotonin-containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post-infectious changes in neuromuscular function. AIM: To evaluate whether steroids reduce the number of enterochromaffin cells and improve the symptoms of post-infectious irritable bowel syndrome. METHODS: Twenty-nine patients with post-infectious irritable bowel syndrome underwent a randomized, double-blind, placebo-controlled trial of 3 weeks of oral prednisolone, 30 mg/day. Mucosal enterochromaffin cells, T lymphocytes and mast cells were assessed in rectal biopsies before and after treatment, and bowel symptoms were recorded in a daily diary. RESULTS: Initial enterochromaffin cell counts were increased and correlated with initial lamina propria T-lymphocyte counts (r = 0.460, P = 0.014). Enterochromaffin cell counts did not change significantly after either prednisolone (- 0.8% +/- 9.2%) or placebo (7.9% +/- 7.9%) (P = 0.5). Although lamina propria T-lymphocyte counts decreased significantly after prednisolone (22.0% +/- 5.6%, P = 0.003), but not after placebo (11.5% +/- 8.6%, P = 0.1), this was not associated with any significant treatment-related improvement in abdominal pain, diarrhoea, frequency or urgency. CONCLUSIONS: Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in post-infectious irritable bowel syndrome. Other approaches to this persistent condition are indicated.     

Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial

BACKGROUND: Herbal medications have been used in many countries for the treatment of patients with irritable bowel syndrome. Controlled data supporting the efficacy of these treatments in patients with irritable bowel syndrome are lacking. AIM: To assess the efficacy and safety of a commercially available herbal preparation (STW 5) (nine plant extracts), the research herbal preparation STW 5-II (six plant extracts) and the bitter candytuft mono-extract in patients with irritable bowel syndrome. METHODS: Two hundred and eight patients with irritable bowel syndrome were recruited after standardized diagnostic work-up into a double-blind, placebo-controlled, multi-centre trial and were randomly assigned to receive one of four treatments: commercially available herbal preparation STW 5 (n = 51), research herbal preparation STW 5-II (n = 52), bitter candytuft mono-extract (n = 53) or placebo (n = 52). The main outcome variables were the changes in total abdominal pain and irritable bowel syndrome symptom scores. RESULTS: Two hundred and three patients completed the trial. STW 5 and STW 5-II were significantly better than placebo in reducing the total abdominal pain score (intention-to-treat: STW 5, P = 0.0009; STW 5-II, P = 0.0005) and the irritable bowel syndrome symptom score (intention-to-treat: STW 5, P = 0.001; STW 5-II, P = 0.0003) at 4 weeks. There were no statistically significant differences between the bitter candytuft mono-extract group and the placebo group (P = 0.1473, P = 0.1207). CONCLUSIONS: The commercially available herbal preparation STW 5 and its research preparation STW 5-II are both effective in alleviating irritable bowel syndrome symptoms.     

Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study

Aliment Pharmacol Ther 2011; 34: 868–877

Summary

Background There is a need for safe and effective treatment options for irritable bowel syndrome (IBS). AST‐120 (spherical carbon adsorbent) is a non‐absorbed, carbon‐based adsorbent with extensive adsorbing capability for histamine, serotonin and other substances implicated in IBS pathogenesis. Aim To evaluate the efficacy and safety of AST‐120 in non‐constipating forms of IBS. Methods This randomised, double‐blind, placebo‐controlled trial conducted in the US and Belgium enrolled 115 male and female patients fulfilling Rome III criteria for IBS; individuals with predominantly constipation symptoms were excluded. Subjects were randomised to AST‐120 2 g tds or placebo for an 8‐week double‐blind treatment period, followed by a 2‐week single‐blind placebo washout and 8‐week single‐blind active treatment. The primary efficacy endpoint was the proportion of subjects achieving at least a 50% reduction in the number of days with abdominal pain compared with baseline. Results At Week 4, 26.8% of subjects treated with AST‐120 responded on the primary endpoint vs. 10.2% in the placebo arm (P = 0.029); at Week 8 response rates were 32.1 and 25.4% respectively (NS). More AST‐120 treated subjects experienced improvement in bloating and stool consistency. These benefits abated when AST‐120 was replaced by placebo, and resumed once AST‐120 was restarted. The frequency of adverse events with AST‐120 were less than or equal to placebo. Conclusions AST‐120 is safe and well‐tolerated and reduces pain and bloating in non‐constipating IBS, although beneficial effects may be limited in duration. AST‐120 represents a locally acting, non‐absorbed, novel treatment for IBS and warrants further studies.     

Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind study

Background  There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype.
Aims  To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study.
Methods  Eligible patients ( n  = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 μg, 300 μg and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment.
Results  Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24% P  = 0.011, 23% P  = 0.005, and 12% after 300 μg, 100 μg and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients ( P  < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used.
Conclusion  ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients.     

Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: results of a double-blind,randomized, placebo-controlled trial

BACKGROUND: Alverine citrate has been used in the treatment of irritable bowel syndrome for many years. AIMS: To compare the efficacy and safety of a new formulation of alverine citrate, a 120-mg capsule, with placebo given three times daily for 12 weeks. METHODS: One hundred and seven patients with irritable bowel syndrome were entered into this three-centre, double-blind, randomized, placebo-controlled, parallel group trial. The primary end-point was relief of abdominal pain indicated by improvement in the scores for severity and frequency. Secondary efficacy variables included scores for other clinical symptoms and for overall well-being. RESULTS: The severity and frequency of abdominal pain improved in 66% and 68% of patients treated with alverine citrate vs. 58% and 69% of the placebo group, but these differences were not significant. The mean percentage reduction in the scores for abdominal pain from baseline to the final assessment, although greater in the alverine citrate group (43.7%) compared with the placebo group (33.3%), was not statistically significant. CONCLUSIONS: Alverine citrate is no better than placebo at relieving the symptoms of irritable bowel syndrome. Future trials should be designed to take into account the high and persistent placebo response seen in this condition.     

Clinical trial: renzapride therapy for constipation-predominant irritable bowel syndrome--multicentre, randomized, placebo-controlled, double-blind study in primary healthcare setting

Background  Relatively few pharmacological treatment options are available for treating patients with irritable bowel syndrome. New and effective medicines are urgently required.
Aim  To identify an appropriate dosage of renzapride (a 5-HT₄ receptor full agonist/5-HT₃ receptor antagonist) to treat abdominal pain/discomfort in patients with constipation-predominant irritable bowel syndrome.
Methods  In this randomized, placebo-controlled, phase IIb study in the primary care setting, men and women were randomized to placebo or renzapride (1, 2 or 4 mg/day) for 12 weeks. The primary outcome measure was patient self-assessed relief of abdominal pain/discomfort during weeks 5–12. Secondary efficacy measures included patients' assessment of their bowel habits, stool consistency and quality of life.
Results  Although there were no statistically significant differences between renzapride and placebo for relief from abdominal pain/discomfort, responder rates in the renzapride treatment groups increased dose dependently, with the 4 mg/day group being consistently numerically greater than placebo. Importantly, a larger numerical treatment difference vs. placebo was observed in women (8% and 12% respectively). Statistically significant improvements in bowel movement frequency and stool consistency were observed in the 4 mg/day group relative to placebo. Renzapride was well tolerated at all doses.
Conclusions  This study confirms the gastrointestinal prokinetic effects of renzparide. The data also suggested a potentially beneficial effect on abdominal pain/discomfort in women with constipation-predominant irritable bowel syndrome.     

A randomized, double-blind, placebo-controlled trial of trazodone hydrochloride in chronic low back pain syndrome

A 6-week placebo-controlled trial evaluated the efficacy of trazodone hydrochloride for the relief of chronic low back pain. Forty-two subjects (22 trazodone, 20 placebo) with a 20.3-year average history of back pain were titrated to an average dose of trazodone 201 mg or placebo 238 mg and evaluated daily on a Visual Analogue Scale of pain intensity, at 2-week intervals on an observer rating of pain behavior while walking, and before and after the trial on the Beck Depression Inventory, the Sickness Impact Profile, and a solid state microcomputer (Vitalog) that measured physical activity. Trazodone blood levels and urine toxicology screens were also obtained. There were no significant differences between groups in treatment effect. The results of this study require confirmation by longer trials with larger, less chronic, more homogeneous samples at higher doses with follow-up assessments.     

Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study

Background  The efficacy of probiotics in alleviating the symptoms of irritable bowel syndrome (IBS) appears to be both strain- and dose-related.
Aim  To investigate the effect of LAB4, a multistrain probiotic preparation on symptoms of IBS. This probiotic preparation has not previously been assessed in IBS.
Methods  Fifty-two participants with IBS, as defined by the Rome II criteria, participated in this double blind, randomized, placebo-controlled study. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10¹⁰ cfu/capsule or a placebo for 8 weeks. Participants reported their IBS symptoms using a questionnaire fortnightly during the intervention and at 2 weeks post-intervention.
Results  A significantly greater improvement in the Symptom Severity Score of IBS and in scores for quality of life, days with pain and satisfaction with bowel habit was observed over the 8-week intervention period in the volunteers receiving the probiotic preparation than in the placebo group.
Conclusion  LAB4 multistrain probiotic supplement may benefit subjects with IBS.     

Symptomatic efficacy of beidellitic montmorillonite in irritable bowel syndrome: a randomized, controlled trial

BACKGROUND: Beidellitic montmorillonite is a purified clay containing a double aluminium and magnesium silicate. AIM: To assess the efficacy and the safety of beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable bowel syndrome (IBS). METHODS: A multicentre, double-blind, placebo-controlled, randomized study with parallel groups, was performed in IBS patients selected according to ROME I criteria. Patients were included after a 1-week washout period to confirm that abdominal pain and/or discomfort was rated at least 2 on a 0-4 graded Likert scale. Patients were then randomized and stratified according to their predominant bowel habit profile into three groups. The use of rescue medication was allowed: polyethylene glycol 4000 (10-20 g/day) as a laxative agent in case of stool absence for three consecutive days, phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no more than 8 days. The main end-point was the improvement of abdominal pain and/or discomfort by at least 1 point on the Likert scale. RESULTS: A total of 524 patients constituted the overall intent-to-treat population (ITT), 263 were assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea-predominant IBS (D-IBS), 83 constipation-predominant IBS (C-IBS), 87 alternating constipation/diarrhoea-IBS (A-IBS); 261 in the placebo group, i.e. 81 D-IBS, 92 C-IBS and 88 A-IBS. Initial analysis in the ITT population demonstrated a higher rate of success with beidellitic montmorillonite (51.7%) when compared with the placebo group (45.2%); however, the difference was not statistically significant. Improvement was significant in C-IBS both in ITT (beidellitic montmorillonite group = 49.4%, placebo group = 31.5%, P < 0.016) and per protocol populations (59.4% vs. 37.8%) (P < 0.01). The time to improvement of abdominal pain and/or discomfort (log Rank test) was also significantly in favour of beidellitic montmorillonite, (P < 0.04). The average number of stools per day was not different from baseline, either in all patients or in C-IBS patients. Spasmolytic and laxative agent intakes were not different between the two groups. Subjective evaluation by patients of treatment efficacy and visual analogue scale test of treatment efficacy by investigators were significantly better in the beidellitic montmorillonite group (P < 0.05). Tolerance of beidellitic montmorillonite was considered optimal without any significant adverse event. CONCLUSIONS: Although pain or discomfort was not significantly improved in the entire IBS population treated with beidellitic montmorillonite in comparison with placebo, this study demonstrates that beidellitic montmorillonite is efficient for C-IBS patients (P < 0.016). This effect of beidellitic montmorillonite on pain cannot be explained by changes in bowel habits. The efficacy of this well-tolerated therapy warrants further confirmatory therapeutic trials in C-IBS patients.     

The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study

BACKGROUND: Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness. AIM: To compare the effects of fluoxetine and placebo in the treatment of pain and constipation-predominant irritable bowel syndrome in a double-blind randomized-controlled trial. METHODS: Forty-four cases meeting Rome II criteria for irritable bowel syndrome with predominance of pain and constipation were included in this study. Organic causes were ruled out by detailed history, physical examination, laboratory tests and colonoscopy. Participants were then randomly assigned to receive either fluoxetine or placebo for 12 weeks. Symptoms addressed by the Rome II criteria were recorded during treatment and 4 weeks after termination of treatment. RESULTS: Fluoxetine was significantly more effective than placebo in decreasing abdominal discomfort, relieving feeling and sense of bloating, increasing frequency of bowel movements and decreasing consistency of stool. Mean number of symptoms per patient decreased from 4.6 to 0.7 in the fluoxetine group vs. 4.5 to 2.9 in controls (P < 0.001). CONCLUSIONS: Fluoxetine is an effective and well-tolerated short-term treatment for pain and constipation-predominant irritable bowel syndrome.     

Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life--a double-blind, placebo-controlled study

Aliment Pharmacol Ther 2011; 33: 1123–1132

Summary

Background Recent research suggests that an imbalance of the intestinal microbiota and a dysfunctional intestinal barrier might trigger irritable bowel syndrome (IBS). As probiotics have been reported to restore the intestinal microbiota and the gut barrier, the therapeutic potential of probiotics within IBS became of strong interest. Aim To assess the efficacy of Bifidobacterium bifidum MIMBb75 in IBS. Methods A total of 122 patients were randomised to receive either placebo (N = 62) or MIMBb75 (N = 60) once a day for 4 weeks. The severity of IBS symptoms was recorded daily on a 7‐point Likert scale. Results MIMBb75 significantly reduced the global assessment of IBS symptoms by ?0.88 points (95% CI: ?1.07; ?0.69) when compared with only ?0.16 (95% CI: ?0.32; 0.00) points in the placebo group (P < 0.0001). MIMBb75 also significantly improved the IBS symptoms pain/discomfort, distension/bloating, urgency and digestive disorder. The evaluation of the SF12 sum scores showed a significant gain in quality of life within the bifidobacteria group. Furthermore, adequate relief was reported by 47% of the patients in the bifidobacteria and only by 11% of the patients in the placebo group (P < 0.0001). Overall responder rates were 57% in the bifidobacteria group but only 21% in the placebo group (P = 0.0001). MIMBb75 was well tolerated and adverse events were not different from placebo. Conclusions Bifidobacterium bifidum MIMBb75 effectively alleviates global IBS and improves IBS symptoms simultaneously with an improvement of quality of life. Considering the high efficacy of MIMBb75 in IBS along with the good side‐effect profile, MIMBb75 is a promising candidate for IBS therapy.

     

Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study

To determine the relative analgesic efficacy of ibuprofen 400 mg and acetaminophen 1000 mg, we conducted a single-dose, double-blind, placebo-controlled, randomized clinical trial using a standard assay for analgesic agents, the dental pain model. At regular intervals over 6 hours, 184 patients who had undergone dental impaction surgery rated pain intensity and relief on categorical scales and pain half-gone on a dichotomous nominal scale; a categorical overall evaluation was completed at the end of 6 hours. Both active agents were effective compared to placebo. Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for Sum Pain Intensity Difference (SPID), Total Pain Relief (TOTPAR), sum pain half-gone, and overall evaluation (P less than .05 to P less than .001). The time-effect curves demonstrated a greater peak effect and longer duration of action for ibuprofen 400 mg compared to acetaminophen 1000 mg. Side effects were reported in five ibuprofen patients, 11 acetaminophen-treated patients, and seven placebo patients. Based on the results of this clinical study, we conclude that ibuprofen 400 mg is a safe and more effective analgesic than acetaminophen 1000 mg for patients with acute pain.     

Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized,double-blind,placebo-controlled pilot study

The aim of this study was to demonstrate the safety and efficacy of H₂-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H₂-dissolved saline (H₂-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H₂-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H₂-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H₂-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H₂ group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H₂ or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H₂ group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H₂ group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H₂ safely and effectively reduced RA disease activity.     

Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome – results of two randomized, placebo-controlled studies

Background Effective treatments for irritable bowel syndrome with constipation (IBS‐C) are lacking. Aim To assess the efficacy and safety of lubiprostone in IBS‐C. Methods A combined analysis was performed among 1171 patients with a Rome II diagnosis of IBS‐C in two phase‐3 randomized trials of lubiprostone 8 mcg vs. placebo twice daily for 12 weeks. Using a balanced seven‐point Likert scale ranging from significantly relieved (+3), to significantly worse (?3), patients responded on their electronic diary to the question: ‘How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?’. The primary efficacy endpoint was the percentage of overall responders. Results Using an intent‐to‐treat analysis with last observation carried forward, a significantly higher percentage of lubiprostone‐treated patients were considered overall responders compared with those treated with placebo (17.9% vs. 10.1%, P = 0.001). Patients treated with lubiprostone reported a similar incidence of adverse events to those treated with placebo. Conclusions The percentage of overall responders based on patient‐rated assessments of IBS‐C symptoms was significantly improved in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo. Lubiprostone was well tolerated with a favourable safety profile.