Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II, randomized, double-blind, placebo-controlled clinical study

Abstract Background The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be involved, we conducted a phase II, randomized, controlled study to evaluate nemolizumab (anti-IL-31 receptor A antibody) in Japanese hemodialysis patients with UP. Methods Patients were randomly assigned (1:1:1:1:1) to one of four double-blind groups (receiving a single subcutaneous injection of nemolizumab 0.125, 0.5, or 2.0 mg/kg, or placebo on Day 1) or an open-label reference group (receiving oral nalfurafine hydrochloride 2.5–5 μg once daily for 12 weeks). The primary endpoint was the difference in the absolute change in pruritus visual analog scale (VAS) at Week 4 between placebo and each nemolizumab group. Results The primary efficacy endpoint was not met. The mean change from baseline with all three nemolizumab doses at Week 1, and with 0.5 mg/kg at Week 4, was greater than with placebo. Least square mean differences (95% confidence intervals) in the absolute changes between the placebo arm and each nemolizumab arm were − 2.4 (− 19.7, 14.9) for 0.125 mg/kg, − 8.7 (− 26.6, 9.2) for 0.5 mg/kg, and 0.4 (− 17.0, 17.8) for 2.0 mg/kg. Secondary efficacy parameters including the Shiratori severity score and 5-D itch score failed to show between-group differences. Patients with higher serum IL-31 levels at screening tended to have greater pruritus VAS reductions following nemolizumab treatment. Conclusions In this phase II study in patients with UP, the primary efficacy parameter was not met. Nemolizumab was generally well tolerated with no clinically significant safety concerns. Clinical trial registration JAPIC: JapicCTI-152961, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-152961.

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A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

BMC Microbiology ◽

10.1186/s12866-021-02230-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Christophe Lay ◽

Collins Wenhan Chu ◽

Rikky Wenang Purbojati ◽

Enzo Acerbi ◽

Daniela I. Drautz-Moses ◽

...

Keyword(s):

Risk Factor ◽

Gut Microbiome ◽

Reference Group ◽

Mode Of Delivery ◽

Controlled Study ◽

Double Blind ◽

Lipopolysaccharide Biosynthesis ◽

Infant Gut Microbiome ◽

Stool Samples ◽

The Impact

Abstract Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838) on 4th April 2011.

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Correction to: Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study

Diabetologia ◽

10.1007/s00125-021-05460-0 ◽

2021 ◽

Author(s):

Linong Ji ◽

Ying Du ◽

Min Xu ◽

Xiangjun Zhou ◽

Zhaohui Mo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Phase Ii ◽

Controlled Study ◽

Efficacy And Safety ◽

Double Blind ◽

Treatment Naïve

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ISA247: Quality of Life Results from a Phase II, Randomized, Placebo-Controlled Study

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2008.07060 ◽

2008 ◽

Vol 12 (6) ◽

pp. 268-275 ◽

Cited By ~ 9

Author(s):

Aditya K. Gupta ◽

Richard G. Langley ◽

Charles Lynde ◽

Kirk Barber ◽

Wayne Gulliver ◽

...

Keyword(s):

Quality Of Life ◽

Phase Ii ◽

Life Quality ◽

Skin Condition ◽

Controlled Study ◽

Double Blind ◽

Plaque Type ◽

Psoriasis Disability Index ◽

Stable Plaque

Background: Psoriasis is a chronic skin condition that can negatively affect a patient's quality of life (QoL), often hindering social functioning. ISA247, a novel psoriatic agent, has shown clinical efficacy in moderate to severe psoriasis sufferers, but its effect on QoL is currently not reported. Objective: The objective of this study was to assess the effect of ISA247 on the QoL in patients with stable, plaque-type psoriasis. Methods: A phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study assessed the effects of ISA247 doses of 0.5 mg/kg/d ( n = 77) or 1.5 mg/kg/d ( n = 83) compared with placebo ( n = 41) for 12 weeks. QoL was assessed using the Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) scales. Results: ISA247 treatment (pooled groups) significantly improved QoL scores as assessed by both the DLQI and the PDI compared with those receiving placebo ( p < .05). Treatment with the higher dose of 1.5 mg/kg/d demonstrated a significantly greater response to many of the QoL scales compared with the 0.5 mg/kg/d group ( p < .05). Conclusions: ISA247 appears to improve the QoL while also providing effective treatment for chronic, moderate to severe, plaque-type psoriasis.

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Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial

Perfusion ◽

10.1177/0267659117715507 ◽

2017 ◽

Vol 32 (7) ◽

pp. 591-597 ◽

Cited By ~ 5

Author(s):

Geoff G. Lockwood ◽

Leilani Cabreros ◽

Dorota Banach ◽

Prakash P. Punjabi

Keyword(s):

Cardiac Surgery ◽

Primary Outcome ◽

Controlled Trial ◽

Morphine Consumption ◽

Controlled Study ◽

Double Blind ◽

Clinical Trial Registration ◽

Subcutaneous Infusion ◽

Randomised Controlled Study ◽

Randomised Controlled

Background: Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Method: Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg-1.hr-1) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. Results: There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l-1. There were no adverse events as a consequence of the study. Conclusion: Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. Clinical trial registration: ISRCTN13424423 ( https://www.isrctn.com )

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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus

American Journal of Nephrology ◽

10.1159/000484573 ◽

2017 ◽

Vol 46 (6) ◽

pp. 450-458 ◽

Cited By ~ 29

Author(s):

Vandana S. Mathur ◽

Jayant Kumar ◽

Paul W. Crawford ◽

Howard Hait ◽

Thomas Sciascia ◽

...

Keyword(s):

Rating Scale ◽

Numerical Rating Scale ◽

Controlled Trial ◽

Hemodialysis Patients ◽

Opioid Antagonist ◽

Opioid Agonist ◽

Double Blind ◽

Double Blind Placebo ◽

Uremic Pruritus ◽

The Mean

Background: Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL. Results: The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively. Conclusions: In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.

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