scholarly journals Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension

2019 ◽  
Vol 90 (11) ◽  
pp. 1244-1250 ◽  
Author(s):  
Yasmine Emma Maria Dreissen ◽  
Joke M Dijk ◽  
Jeannette M Gelauff ◽  
Evelien Zoons ◽  
Daniël van Poppelen ◽  
...  
Keyword(s):  
Movement Disorders ◽  
Botulinum Neurotoxin ◽  
Primary Outcome ◽  
Psychiatric Symptoms ◽  
Controlled Trial ◽  
Open Label ◽  
Double Blind ◽  
Functional Movement ◽  
Open Label Phase ◽  
Functional Movement Disorders

ObjectiveTo study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).MethodsPatients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase.ResultsBetween January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI −0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline.ConclusionsIn this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients.Trial registration numberNTR2478

Donepezil for Cancer Fatigue: A Double-Blind, Randomized, Placebo-Controlled Trial

2007 ◽  
Vol 25 (23) ◽  
pp. 3475-3481 ◽  
Author(s):  
Eduardo Bruera ◽  
Badi El Osta ◽  
Vicente Valero ◽  
Larry C. Driver ◽  
Be-Lian Pei ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Final Analysis ◽  
Symptom Assessment ◽  
Subscale Score ◽  
Assessment System ◽  
Open Label ◽  
Double Blind ◽  
Fatigue Score ◽  
Significant Difference ◽  
Open Label Phase

PurposeTo evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy–Fatigue (FACIT-F).Patients and MethodsPatients with fatigue score ≥ 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) for more than 1 week were included. Patients were randomly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days. A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level. All patients were offered open-label donepezil during the second week. FACIT-F and/or the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 11, and 15. The FACIT-F fatigue subscale score on day 8 was considered the primary end point.ResultsOf 142 patients randomly assigned to treatment, 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis. Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .57) or ESAS (P = .18) between groups. In the open-label phase, fatigue intensity continued to be low as compared with baseline. No significant toxicities were observed.ConclusionDonepezil was not significantly superior to placebo in the treatment of cancer-related fatigue.

scholarly journals Gastrointestinal Tract Microbiome Dynamics Following Treatment with SER-109, an Investigational Oral Microbiome Therapeutic to Reduce the Recurrence of Clostridium difficile Infection (CDI)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S389-S390 ◽  
Author(s):  
Matthew Henn ◽  
Christopher Ford ◽  
Edward O’Brien ◽  
Jennifer Wortman ◽  
Sheri Simmons ◽  
...  
Keyword(s):  
Stock Options ◽  
Controlled Trial ◽  
Post Treatment ◽  
Oral Microbiome ◽  
Biologically Active ◽  
Open Label ◽  
Double Blind ◽  
Significant Difference ◽  
Open Label Phase ◽  
Favorable Clinical Outcome

Abstract Background Recurrence of CDI occurs within a few weeks after treatment due to antibiotic-induced dysbiosis. SER-109, an investigational, first-in-class microbiome drug, was designed to sustain a clinical response through microbiome restoration with a purified ecology of spores. In an open-label Phase 1b (Ph1b) trial of SER-109 for prevention of recurrent CDI, 26 of 30 subjects did not recur following treatment. In a Phase 2 (Ph2) double-blind controlled trial of SER-109 (n = 59) vs. placebo (n = 30), no significant difference was observed in the proportions of subjects with recurrence (44.1% vs. 53.3%, respectively). Here we contrast gut microbiome changes among subjects in both trials to understand differences in clinical outcomes observed 8-weeks after dosing. Methods We used 16S v4 and high-resolution whole metagenomic shotgun (WMS) sequencing to characterize microbiome changes from stool samples collected at baseline and 1, 4, and 8 weeks post-treatment. Microbiome analyses focused on subjects diagnosed with recurrence via EIA toxin testing (high confidence recurrence; HCR). Results Significantly greater richness of commensal spore-former species was observed in Ph2 subjects treated with SER-109 compared with PBO at weeks 1 and 4 post-treatment (Mann–Whitney P = 0.008, P = 0.044 respectively) consistent with drug engraftment. In addition, the number of spore-forming species at 1 week post-treatment was significantly greater in non-recurrent subjects vs. HCR subjects (Mann–Whitney P = 0.011). Furthermore, we identified 10 spore-former species that were significantly more prevalent in both SER-109 and non-recurrent subjects (Fig 1). In comparison to Ph1 subjects, SER-109 engraftment was significantly reduced and delayed among Ph2 subjects at all time points (Fig 2). Moreover, Ph1b subjects who received higher doses of SER-109 than that used in Ph2 had increased levels of engraftment. Conclusion In patients with recurrent CDI and dysbiosis, a focused spore-based therapeutic approach leads to engraftment of SER-109 strains. In addition, microbiome signatures of engraftment were associated with a favorable clinical outcome. Although SER-109 was biologically active, a higher dose may improve the rate and degree of microbiome repair. Disclosures M. Henn, Seres Therapeutics: Employee and Shareholder, Salary and Stock Options; C. Ford, Seres Therapeutics: Employee and Shareholder, Salary and Stock Options; E. O’Brien, Seres Therapeutics: Employee and Shareholder, Salary and Stock Options; J. Wortman, Seres Therapeutics: Employee and Shareholder, Salary and Stock Options; S. Simmons, Seres Therapeutics: Employee and Shareholder, Salary and Stock options; L. Diao, Seres Therapeutics: Employee and Shareholder, Salary and Stock; K. Litcofsky, Seres Therapeutics: Employee and Shareholder, Salary and stock options; P. Bernardo, Seres Therapeutics: Employee and Shareholder, Salary and Stock options; J. Aunins, Seres Therapeutics, Inc.: Employee and Shareholder, Salary and Stock options; D. Cook, Seres Therapeutics: Employee and Shareholder, Salary and Stock Options; M. Trucksis, Seres Therapeutics Inc.: Employee and Shareholder, Salary and stock options

scholarly journals Efficacy and Safety of OnabotulinumtoxinA 400 Units in Patients with Post-Stroke Upper Limb Spasticity: Final Report of a Randomized, Double-Blind, Placebo-Controlled Trial with an Open-Label Extension Phase

Toxins ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 127
Author(s):  
Masahiro Abo ◽  
Takashi Shigematsu ◽  
Hiroyoshi Hara ◽  
Yasuko Matsuda ◽  
Akinori Nimura ◽  
...  
Keyword(s):  
Upper Limb ◽  
Muscle Tone ◽  
Controlled Trial ◽  
Final Report ◽  
Elbow Flexors ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Phase ◽  
Limb Spasticity

In many countries, 400 units (U) is the maximum dose of onabotulinumtoxinA available to treat upper limb spasticity, but few studies have demonstrated the optimal use of this dose. In the double-blind phase of this randomized, controlled trial, we compared the efficacy and safety of 400 vs. 240 U onabotulinumtoxinA in patients with post-stroke upper limb spasticity. Both groups received 240 U onabotulinumtoxinA injected in the forearm. An additional 160 U onabotulinumtoxinA (400 U group) or placebo (240 U group) was injected in the elbow flexors. Both groups showed similar muscle tone reduction in the wrist, fingers, and thumb; muscle tone reduction in the elbow flexors was greater in the group treated with onabotulinumtoxinA (400 U group) compared to placebo (240 U group). Functional disabilities improved in both groups. No substantial difference was found in safety profiles. In the subsequent open-label phase, all participants received repeat injections of 400 U onabotulinumtoxinA (target muscles and doses per muscle determined by the physician). Similar efficacy and safety outcomes, as with the 400 U group in the double-blind phase, were confirmed. This final report demonstrates that injection of onabotulinumtoxinA 400 U relieves muscle tone in a wide range of areas and improves functional disabilities; generally, it was well-tolerated, and no new safety concerns were identified. The dosing data in the open-label phase will inform optimal use of onabotulinumtoxinA in clinical practice (ClinicalTrials.gov: NCT03261167).

scholarly journals Effects of cerebello-spinal stimulation in neurodegenerative ataxia on motor and cognitive outcomes: a randomized, double-blind, sham-controlled trial followed by an open-label phase

2021 ◽  
Vol 14 (6) ◽  
pp. 1589
Author(s):  
Alberto Benussi ◽  
Valentina Cantoni ◽  
Marta Manes ◽  
Ilenia Libri ◽  
Valentina Dell'Era ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Cognitive Outcomes ◽  
Open Label ◽  
Double Blind ◽  
Open Label Phase

scholarly journals Botulinum neurotoxin (BoNT) treatment in functional movement disorders: long-term follow-up

2020 ◽  
Vol 91 (10) ◽  
pp. 1120-1121
Author(s):  
Yasmine EM Dreissen ◽  
Franka Lambert ◽  
Joke M Dijk ◽  
Johannes HTM Koelman ◽  
Marina AJ Tijssen
Keyword(s):  
Movement Disorders ◽  
Botulinum Neurotoxin ◽  
Functional Movement ◽  
Long Term Follow Up ◽  
Functional Movement Disorders

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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