Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial

Objective: The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. Study Design: The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. Setting: The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. Interventions: Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. Outcomes: The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. Results: 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (n = 65) or a placebo (n = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, p = 0.0272 [p = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (p = 0.007 [p = 0.0107]). Conclusions: Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.

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Efficacy and Safety of Divaza for The Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial

10.21203/rs.3.rs-63542/v1 ◽

2020 ◽

Author(s):

Victoria V. Fateeva ◽

Nataliia U. Lashch ◽

Pavel R. Kamchatnov ◽

Tatiana N. Fedorova ◽

Olga A. Muzychuk ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Placebo Group ◽

Controlled Trial ◽

Compliance Rate ◽

Prospective Trial ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Cerebral Atherosclerosis ◽

Endogenous Antioxidant

Abstract Objective: To determine if Divaza was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. Study design: 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups.Setting: 10 clinical centers across the Russian Federation.Interventions: Patients were randomized into two groups and instructed to take either 2 tablets of the study drug or placebo 3 times per day in conjunction with basic therapy. Outcomes: The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The laboratory indicators of oxidative stress were analyzed at baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study.Results: 124 outpatients with a mean age of 60.7±7.6 years were enrolled and randomly assigned to receive Divaza (n=65) or placebo (n=59). The Administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8±14.7 [14.8±14.7] seconds latent period versus 6.4±16.9 [6.9±16.7] seconds in the placebo group (p=0.007 [p=0.0107]). In addition, a recovery of cognitive impairment was observed in all patients of the Divaza group at the end of treatment; this was significantly better when compared with the placebo group (100 [100] % versus 89.5 [89.1] %, respectively, p=0.0272 [p=0.0128]). The treatment was safe, well-tolerated, and had a high compliance rate. Conclusions: Divaza is a safe and effective therapeutic option for attenuating oxidative stress and recovery of cognitive impairment in patients with cerebral atherosclerosis.Trial registration: clinicaltrials.gov NCT03485495, of April 02, 2018.

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A Randomised, Double-Blind, Placebo-Controlled Trial of Actovegin in Patients with Post-Stroke Cognitive Impairment: ARTEMIDA Study Design

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000357122 ◽

2013 ◽

Vol 3 (1) ◽

pp. 459-467 ◽

Cited By ~ 11

Author(s):

Alla Guekht ◽

Ingmar Skoog ◽

Amos D. Korczyn ◽

Vladimir Zakharov ◽

Martin Eeg ◽

...

Keyword(s):

Cognitive Impairment ◽

Study Design ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Post Stroke

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Safety and efficacy of herbal medicine for acute intracerebral hemorrhage (CRRICH): a multicentre randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2018-024932 ◽

2019 ◽

Vol 9 (5) ◽

pp. e024932 ◽

Cited By ~ 4

Author(s):

Liling Zeng ◽

Guanghai Tang ◽

Jing Wang ◽

Jianbin Zhong ◽

Zhangyong Xia ◽

...

Keyword(s):

Placebo Group ◽

Herbal Medicine ◽

Adverse Events ◽

Intracerebral Haemorrhage ◽

Poor Prognosis ◽

Controlled Trial ◽

Blood Stasis ◽

Secondary Outcome ◽

Controlled Study ◽

Safety And Efficacy

ObjectiveTo evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window.Study designA randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China.Participants and interventionsPatients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset.OutcomesThe primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset.ResultsA total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group.ConclusionsUltra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1.Trialregistration numberNCT01918722.

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Effect of Baduanjin exercise on cognitive function in patients with post-stroke cognitive impairment: a randomized controlled trial

Clinical Rehabilitation ◽

10.1177/0269215520930256 ◽

2020 ◽

Vol 34 (8) ◽

pp. 1028-1039 ◽

Cited By ~ 2

Author(s):

Guohua Zheng ◽

Yuhui Zheng ◽

Zhenyu Xiong ◽

Bingzhao Ye

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Outcome Measures ◽

Daily Living ◽

Controlled Trial ◽

Secondary Outcome ◽

Control Group ◽

Rehabilitation Treatment ◽

Global Cognitive Function ◽

Delayed Recognition

Objective: To investigate the effectiveness and safety of Baduanjin training on the cognitive function in stroke survivors with cognitive impairment. Design: A randomized, two-arm parallel controlled trial with allocation concealment and assessors blinding. Setting: Community centre of Fuzhou city, China. Subjects: A total of 48 participants were recruited and randomly allocated into the Baduanjin exercise intervention or control group. Interventions: The control group maintained original medication and rehabilitation treatment. The Baduanjin training group received 24-week Baduanjin training with a frequency of three days a week and 40 minutes a day based on original medication and rehabilitation treatment. Main outcome measures: The primary outcome was global cognitive function. Secondary outcome measures included the specific domains of cognition (i.e. memory, processing speed, execution, attention and visuospatial ability) and activities daily living. Results: In total, 41 (Baduanjin n = 22, control n = 19) participants completed 24-week treatment and data collection. Mean differences between groups at 24-week treatment were statistically significant for global cognitive function (MoCA: 2.54 (0.91 to 4.16)), execution (TMT-A: −42.4 (−75.0 to −9.8); TMT-B: −71.3 (−130.6 to −12.1)), memory (immediate recall: 2.11 (0.49 to 3.73); short-term delayed recognition: 2.47 (0.58 to 4.35) and long-term delayed recognition: 1.68(0.18 to 3.17)), attention (response time of alertness: −245.5 (−387 to −104)) and activities of daily living (modified Barthel Index). Conclusion: Regular Baduanjin training is associated with less loss of cognitive function in patients after stroke.

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Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI

International Psychogeriatrics ◽

10.1017/s1041610207005650 ◽

2008 ◽

Vol 20 (1) ◽

pp. 40-46 ◽

Cited By ~ 10

Author(s):

Stephen Salloway ◽

Stephen Correia ◽

Sharon Richardson

Keyword(s):

Cognitive Impairment ◽

Outcome Measures ◽

Primary Outcome ◽

Rating Scales ◽

Controlled Trial ◽

Term Treatment ◽

Lessons Learned ◽

Secondary Outcome ◽

Short Term ◽

Short Term Treatment

ABSTRACTObjective: This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI).Methods: The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group.Results: There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups.Conclusions: The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.

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A Randomized Controlled Trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in the treatment of chronic tension-type facial pain

Rhinology Journal ◽

10.4193/rhino12.187 ◽

2013 ◽

Vol 51 (2) ◽

pp. 143-153

Author(s):

A.M. Agius ◽

N.S. Jones ◽

R. Muscat

Keyword(s):

Facial Pain ◽

Serotonin Receptor ◽

Low Dose ◽

Controlled Trial ◽

Tension Type Headache ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Onset Of Action ◽

10Mg Daily ◽

Pain Scores

Background: Patients often present to otolaryngologists with chronic facial pain, presumed to be of sinus origin despite normal nasal endoscopy and sinus CT. This pain has increasingly been recognized as being of neurological origin with one of the commonest underlying causes being mid-facial segmental tension-type pain (MFP) which is a version of tension-type headache affecting the midface. Primary outcome measures: 1. To determine whether low-dose amitriptyline reduces pain scores compared to surrogate placebo in patients with chronic MFP. 2. To determine whether the addition of pindolol, a beta blocker with serotonin receptor blocking properties hastens onset of action or improves efficacy of amitriptyline. Secondary outcome measure: to determine whether amitriptyline or amitriptyline with pindolol significantly reduces analgesic consumption. Methodology: Sixty two patients were randomized to three treatment groups (a) amitriptyline 10mg daily (b) amitriptyline 10mg daily with pindolol 5mg twice daily and (c) loratadine 10mg daily. Daily pain scores using a facial pain diary were recorded over eight weeks. Results: At 8 weeks, pain frequency and intensity were significantly reduced in patients treated with amitriptyline and in those receiving amitriptyline with pindolol compared to surrogate placebo. Patients on the combination therapy showed significantly improved clinical outcome and significantly reduced analgesic intake compared to those on amitriptyline alone. Conclusion: Low dose amitriptyline is effective in the management of MFP and is enhanced by the addition of pindolol.

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Effects of different acupuncture treatment methods on post-stroke cognitive impairment: study protocol for a multicenter randomized controlled trial

10.21203/rs.3.rs-31545/v1 ◽

2020 ◽

Author(s):

Kai-Qi Su ◽

Su-Tong Liu ◽

Jie-Ying Li ◽

Rui-Qing Li ◽

Hui-Li Feng ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cognitive Rehabilitation ◽

Acupuncture Treatment ◽

Controlled Trial ◽

Secondary Outcome ◽

Treatment Methods ◽

Post Stroke ◽

Randomized Controlled

Abstract Background: Cognitive impairment is one of common dysfunctions after stroke, which seriously affects the overall recovery of patients. Cognitive rehabilitation training is currently the main treatment to improve cognitive function, but its curative effect is limited. Acupuncture is a core component of traditional Chinese medicine (TCM) and some previous clinical studies have shown that it might be effective in treating post-stroke cognitive impairment (PSCI), but further evidence from large-sample studies is needed. The overall objective of this trial is to obtain further data for forming an optimized acupuncture treatment for PSCI by comparing the effects of different acupuncture treatment methods on cognitive function in PSCI patients.Methods/Design: In this multicenter, prospective, randomized controlled trial, 206 eligible stroke inpatients who meet the trial criteria will be randomly assigned to 2 groups: Electroacupuncture (EA) plus needle retaining (NR) group and EA group, both groups of patients undergo the same routine cognitive rehabilitation treatments. All treatments will be given 6 times per week for 8 weeks. The primary outcomes will be assessed using the Mini Mental State Scale (MMSE) and the Montreal Cognition Assessment Scale (MOCA). The secondary outcome will be measured by the Bathel Index (BI). All outcomes will be evaluated at baseline, week 4, week 8, and the third and sixth month after the end of treatments.Discussion: Our aim is to evaluate the effects of two different acupuncture treatment methods for treating PSCI patients. This study is expected to provide data to be used in developing an optimized acupuncture treatment method for PSCI treatment.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900027849. Registered on 30 November 2019, http://www.chictr.org.cn/showproj.aspx?proj=46316

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Single versus dual Kirschner wires for closed reduction and intramedullary nailing of displaced fractures of the fifth metacarpal neck (1-2 KiWi): a randomized controlled trial

The Bone & Joint Journal ◽

10.1302/0301-620x.101b10.bjj-2019-0410.r1 ◽

2019 ◽

Vol 101-B (10) ◽

pp. 1263-1271 ◽

Cited By ~ 1

Author(s):

Andreas Eisenschenk ◽

Romy Spitzmüller ◽

Claas Güthoff ◽

Adrian Obladen ◽

Simon Kim ◽

...

Keyword(s):

Intramedullary Nailing ◽

Controlled Trial ◽

Kirschner Wire ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Single Wire ◽

Rotational Malalignment ◽

Intention To Treat ◽

Randomized Controlled ◽

Related Quality

Aims The aim of this study was to investigate whether clinical and radiological outcomes after intramedullary nailing of displaced fractures of the fifth metacarpal neck using a single thick Kirschner wire (K-wire) are noninferior to those of technically more demanding fixation with two thinner dual wires. Patients and Methods This was a multicentre, parallel group, randomized controlled noninferiority trial conducted at 12 tertiary trauma centres in Germany. A total of 290 patients with acute displaced fractures of the fifth metacarpal neck were randomized to either intramedullary single-wire (n = 146) or dual-wire fixation (n = 144). The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire six months after surgery, with a third of the minimal clinically important difference (MCID) used as the noninferiority threshold. Secondary outcomes were pain, health-related quality of life (EuroQol five-dimensional questionnaire (EQ-5D)), radiological measures, functional deficits, and complications. Results Overall, 151/290 of patients (52%) completed the six months of follow-up, leaving 83 patients in the single-wire group and 68 patients in the dual-wire group. In the modified intention-to-treat analysis set, mean DASH scores six months after surgery were 3.8 (sd 7.0) and 4.4 (sd 9.4), respectively. With multiple imputation (n = 288), mean DASH scores were estimated at 6.3 (sd 8.7) and 7.0 (sd 10.0). Upper (1 - 2α)) confidence limits consistently remained below the noninferiority margin of 3.0 points in the DASH instrument. While there was a statistically nonsignificant trend towards a higher rate of shortening and rotational malalignment in the single wire group, no statistically significant differences were observed across groups in any secondary outcome measure. Conclusion A single thick K-wire is sufficient for intramedullary fixation of acute displaced subcapital fractures of the fifth metacarpal neck. The less technically demanding single-wire technique produces noninferior clinical and radiological outcomes compared with the dual-wire approach. Cite this article: Bone Joint J 2019;101-B:1263–1271

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Mindfulness-Based Training Does Not Improve Neuropsychological Outcomes in Mild Cognitive Impairment More Than Spontaneous Reversion Rates: A Randomized Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-215035 ◽

2021 ◽

pp. 1-10

Author(s):

Kinjal Doshi ◽

Stacey Lee Henderson ◽

Qianqian Fan ◽

Kian Foong Wong ◽

Julian Lim

Keyword(s):

Randomized Controlled Trial ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Functioning ◽

Cognitive Rehabilitation ◽

Controlled Trial ◽

Secondary Outcome ◽

Group Setting ◽

Randomized Controlled ◽

Spontaneous Reversion

Background: Current pharmacological and behavioral treatment options for mild cognitive impairment (MCI) are limited, motivating a search for alternative therapies that might slow the progression of cognitive decline. Objective: We investigated the effectiveness of a cognition-focused mindfulness-based intervention. Methods: An open-label, three arm randomized controlled trial was conducted at a public tertiary medical center. Older persons (ages 45–75; N = 76) diagnosed with MCI were recruited and randomized into either Mindfulness-based training (MBT), cognitive rehabilitation therapy (CRT), or treatment as usual (TAU). Participants in the intervention arms received 8 weekly 2-h sessions delivered in a group setting and engaged in home practice. Primary outcomes measures included changes in index scores for attention, immediate memory, and delayed memory as measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Depression was a secondary outcome. Results: Using intent-to-treat analysis, we found that participants receiving MBT showed significant improvements in global cognition (d = 0.26; [95%CI 0.03–0.56]) and delayed memory (d = 0.36; [95%CI 0.17–0.57]), with significantly greater improvements in delayed memory than CRT (ηp2 = 0.10). However, there was no benefit of MBT over TAU. No change in depression was observed in the MBT group. Reductions in depression were associated with improvements in cognitive functioning in the MBT group only. Conclusion: Our results suggest that a cognition-focused MBT did not improve cognitive functioning in MCI patients substantially more than spontaneous reversion rates, possibly as mood symptoms were not significantly alleviated in this group.

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Impact of a Pozzi tenaculum forceps use on the success rate of intrauterine insemination (IUI) : protocol for a randomised control trial

BMJ Open ◽

10.1136/bmjopen-2020-043230 ◽

2021 ◽

Vol 11 (3) ◽

pp. e043230

Author(s):

Stephanie Dufour ◽

Mathieu Viau ◽

Maxime Côté ◽

Jessica Lefebvre ◽

Sarah Maheux-Lacroix ◽

...

Keyword(s):

Intrauterine Insemination ◽

Therapeutic Option ◽

Controlled Trial ◽

Research Abstract ◽

Randomised Control Trial ◽

Secondary Outcome ◽

Success Rates ◽

Male Factor ◽

Global Satisfaction ◽

Uterine Contractions

IntroductionA therapeutic option frequently proposed for infertility is to proceed first with intrauterine insemination (IUI) cycles. Little is known on the effect of uterine contractions on IUI success rates. We postulated that uterine contractions may help with sperm migration in the women’s genital tract. Our objective is to compare the efficacy of IUI when performed with and without a tenaculum forceps on the cervix.Methods and analysisWe are conducting a randomised controlled trial with women aged 18–40 years old, diagnosed with primary or secondary infertility due to endometriosis, mild to moderate male factor, unexplained infertility or ovulatory dysfunction, receiving IUI treatments. On the day of their IUI, women will receive standard care treatment plus or minus the planned use of a Pozzi tenaculum forceps on the cervix. Each of the 800 women will be randomised only once for their first three IUI. They will be randomised in one of the following sequences: tenaculum—no tenaculum—tenaculum or, no tenaculum—tenaculum—no tenaculum. We will compare the live birth rate (primary outcome) and the clinical pregnancy rate (secondary outcome) after IUI treatment. We also plan on assessing global satisfaction of women, pain levels felt during IUI and discrepancies in primary and secondary outcomes in interventions performed by attendings compared with trainees.Ethics and disseminationThis research project was approved by the Centre Hospitalier Universitaire de Québec’s ethics review board (no 2018–4084). Pozzi tenaculum application is associated with mild pain, estimated at 33 on a Visual Analogue Scale ranging from 0 to 100. We plan on publishing an article to present our findings in a peer-reviewed journal as well as presenting the research abstract at conferences.Trial registration numberNCT03435809.

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