scholarly journals Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study

2015 ◽  
Vol 75 (6) ◽  
pp. 1009-1015 ◽  
Author(s):  
Eric Hachulla ◽  
Pierre-Yves Hatron ◽  
Patrick Carpentier ◽  
Christian Agard ◽  
Emmanuel Chatelus ◽  
...  
Keyword(s):  
Placebo Group ◽  
Systemic Sclerosis ◽  
Healing Rate ◽  
Controlled Study ◽  
Digital Ulcer ◽  
Cox Models ◽  
Intention To Treat ◽  
End Point ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

ObjectiveTo assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc).MethodsRandomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05).ResultsIntention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).ConclusionsThe primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit.Trial registration numberNCT01295736.

scholarly journals Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Tsuyoshi Miyaoka ◽  
Motohide Furuya ◽  
Jun Horiguchi ◽  
Rei Wake ◽  
Sadayuki Hashioka ◽  
...  
Keyword(s):  
Placebo Group ◽  
Controlled Trial ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Treatment Resistant ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Intention To Treat ◽  
The Difference ◽  
The Individual

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted.Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54:−0.23±0.08; placebo:−0.03±0.08,P<0.018), tension (TJ-54:−0.42±0.09; placebo:−0.18±0.09,P<0.045), and poor impulse control (TJ-54:−0.39±0.10; placebo:−0.07±0.10,P<0.037).Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

A Randomised, Double-Blinded, Placebo-Controlled Study of the Phosphodiesterase Type 5 Inhibitor Sildenafil for the Treatment of Preeclampsia

2009 ◽  
Vol 28 (4) ◽  
pp. 369-382 ◽  
Author(s):  
Rebekah A. Samangaya ◽  
Gary Mires ◽  
Andrew Shennan ◽  
Laurence Skillern ◽  
David Howe ◽  
...  
Keyword(s):  
Controlled Study ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type ◽  
Double Blinded

scholarly journals Muscle Damage in Systemic Sclerosis and CXCL10: The Potential Therapeutic Role of PDE5 Inhibition

2021 ◽  
Vol 22 (6) ◽  
pp. 2894
Author(s):  
Clarissa Corinaldesi ◽  
Rebecca L. Ross ◽  
Giuseppina Abignano ◽  
Cristina Antinozzi ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Muscle Damage ◽  
Nuclear Factor Κb ◽  
Clinical Severity ◽  
Muscle Involvement ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Potential Therapeutic Role ◽  
Chemokine Ligand ◽  
Phosphodiesterase Type

Skeletal muscle damage is a common clinical manifestation of systemic sclerosis (SSc). C-X-C chemokine ligand 10 (CXCL10) is involved in myopathy and cardiomyopathy development and is associated with a more severe SSc prognosis. Interestingly, the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil reduces CXCL10 sera levels of patients with diabetic cardiomyopathy and in cardiomyocytes. Here, we analyzed the levels of CXCL10 in the sera of 116 SSc vs. 35 healthy subjects and explored differences in 17 SSc patients on stable treatment with sildenafil. CXCL10 sera levels were three-fold higher in SSc vs. healthy controls, independent of subset and antibody positivity. Sildenafil treatment was associated with lower CXCL10 sera levels. Serum CXCL10 strongly correlated with the clinical severity of muscle involvement and with creatine kinase (CK) serum concentration, suggesting a potential involvement in muscle damage in SSc. In vitro, sildenafil dose-dependently reduced CXCL10 release by activated myocytes and impaired cytokine-induced Signal transducer and activator of transcription 1 (STAT1), Nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) phosphorylation. This was also seen in cardiomyocytes. Sildenafil-induced CXCL10 inhibition at the systemic and human muscle cell level supports the hypothesis that PDE5i could be a potential therapeutic therapy to prevent and treat muscle damage in SSc.

Can the combined treatment of solifenacin and imipramine has a role in desmopressin refractory monosymptomatic nocturnal enuresis? A prospective double-blind randomized placebo-controlled study

2021 ◽  
pp. 039156032199358
Author(s):  
Mohamed Samir ◽  
Mahmoud A Mahmoud ◽  
Hossam Elawady
Keyword(s):  
Placebo Group ◽  
Treatment Group ◽  
Side Effects ◽  
Relapse Rate ◽  
Nocturnal Enuresis ◽  
Combined Treatment ◽  
Controlled Study ◽  
Common Disease ◽  
End Point ◽  
Monosymptomatic Nocturnal Enuresis

Background: Nocturnal enuresis is a common disease of childhood. It can be classified into monosymptomatic nocturnal enuresis (MNE) or nonmonosymptomatic nocturnal enuresis (NMNE). Imipramine is a tricyclic antidepressant used to treat enuresis with initial success rates are high as 50% but some studies record a high relapse rate and it has a cardiotoxic effect when overdosed. Anticholinergics may be effective in the treatment of children with bladder storage dysfunction, including daytime incontinence. However, anticholinergics monotherapy is not effective in treating MNE. In our study, we used a low dose (25 mg) of imipramine in order to avoid its potential side effects and combined it with the synergistic anticholinergic action of solifenacin. Our objective was to evaluate the efficacy and safety of the combination of solifenacin and imipramine compared with placebo in the treatment of desmopressin refractory MNE. Methods: One hundred children aged 6 years or more with primary MNE unresponsive to desmopressin treatment were included. The children were randomly divided into two equal groups. Group A received imipramine 25 mg and solifenacin 5–10 mg oral tablets and group B received placebo once 1 h before bedtime for 3 months. The primary end point was to investigate the efficacy of the combined treatment of solifenacin and imipramine and the secondary end point was the safety of the drugs. Results: Our study showed that the mean post treatment wet nights per month was significantly lesser in the treatment group than placebo group ( p < 0.001) and cure rate was significantly higher in treatment group than placebo group ( p < 0.001). The relapse rate was statistically significantly lower in treatment group than placebo group ( p = 0.032). No significant side effects related to the drugs were reported. Conclusion: The combination treatment of solifenacin and imipramine is a useful and safe treatment for nocturnal enuresis after failure of everything else.

scholarly journals The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 786
Author(s):  
Luigi Di Luigi ◽  
Guglielmo Duranti ◽  
Ambra Antonioni ◽  
Paolo Sgrò ◽  
Roberta Ceci ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Systemic Sclerosis ◽  
Cell Viability ◽  
Redox Homeostasis ◽  
Dermal Fibroblasts ◽  
Oxygen Species ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type ◽  
Oxidative Insult

Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by the increased deposition of extracellular matrix proteins such as collagen and fibronectin. Although the pathogenesis is not completely understood, a number of studies suggest that free radicals could be the major contributors to the disease. Indeed, different studies demonstrated how oxidative stress could contribute to the fibrotic process activation at the level of the skin and visceral organs. Emerging evidences highlight the beneficial effects of sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), which protects different cell lines from the cell damage induced by reactive oxygen species (ROS). These data make sildenafil a good candidate for therapeutic treatment aimed to protect biological macromolecules against oxidative damage, thus preserving cell viability. The purpose of this study was to evaluate the sensitivity of SSc dermal fibroblasts to an oxidative insult and the ability for sildenafil to prevent/reduce the DNA damage due to ROS action. Additionally, we evaluated the capacity for sildenafil to influence redox homeostasis and cytotoxicity, as well as cell proliferation and cell cycle progression. We demonstrated that SSc fibroblasts have an increased sensitivity to a pro-oxidant environment in comparison to healthy controls. The sildenafil treatment reduced ROS-induced DNA damage, counteracted the negative effects of ROS on cell viability and proliferation, and promoted the activity of specific enzymes involved in redox homeostasis maintenance. To our knowledge, in this report, we demonstrate, for the first time, that sildenafil administration prevents ROS-induced instability in human dermal fibroblasts isolated by SSc patients. These results expand the use of PDE5i as therapeutic agents in SSc by indicating a protective role in tissue damage induced by oxidative insult.

Sign in / Sign up

Export Citation Format

Share Document