Double-blind Crossover Trial Research Articles

Digital versus conventional complete dentures: A randomized, controlled, double-blinded crossover trial

Statement of problemThe Baltic Denture System provides a digital way to fabricate complete dentures in 2 visits. Conventional dentures using injection or compression molding require additional visits and complex laboratory procedures. However, how the fabrication method affects clinical outcomes is unclear. PurposeThe purpose of this clinical, randomized, controlled, double-blinded crossover trial was to evaluate the impact of the fabrication method (digital versus conventional production) of complete dentures on clinical outcomes. Material and methodsSixteen participants received 2 pairs of new complete dentures, produced in a digital and a conventional workflow. Each complete denture was worn for an observation period of 3 months. The order of the dentures was randomized. The primary outcome was the clinical assessment of the dentures by a blinded examiner, including peripheral extension, cutout for buccal and labial frenula, denture extension, and denture thickness. Denture esthetics were evaluated by the midline, position of anterior teeth, buccal corridor, and smile arc, and occlusal relationships were evaluated by the vertical dimension, sagittal relation, the Camper plane, and occlusion. In addition, the retention of maxillary and mandibular dentures and phonetics was evaluated. Differences between the prostheses were statistically analyzed with the McNemar test (α=.05). ResultsThe borders of the digital dentures were significantly more often overextended at the time of insertion (P=.021), reducing the retention of the digital dentures, especially the maxillary dentures (P=.016). The borders of the dentures could be corrected so that after 2 weeks and 3 months, no significant differences could be seen between digital dentures and conventional dentures. ConclusionsThe fabrication method has a significant influence only on the dimension of the denture border. It was significantly more often overextended in digital dentures and impaired retention, especially of the maxillary dentures, at the time of insertion. As this parameter is correctable, no significant clinical differences could be observed over the observation time of 3 months between digital dentures and conventional dentures.

Consumption of Farmed Fish, Fed with an Olive-Pomace Enriched Diet, and Its Effect on the Inflammatory, Redox, and Platelet-Activating Factor Enzyme Profile of Apparently Healthy Adults: A Double-Blind Randomized Crossover Trial.

A fish-rich diet has a beneficial effect on cardiovascular health. The platelet activating factor (PAF) is involved in the development of atherosclerosis, and in vitro results support the regulating action of bioactive nutrients on PAF metabolism. The purpose of this study is to examine whether the consumption of farmed fish fed with an olive-pomace enriched diet (EF) affects PAF metabolism and the markers of inflammation and oxidative stress compared to the consumption of conventionally fed farmed fish (CF). Thirty apparently healthy adults completed a randomized double-blind crossover trial, during which they consumed both CF and EF twice a week for 8 weeks with a six-week washout period in between. The activities of PAF acetylhydrolase (PAF-AH), lysoPAF acetyltransferase (lysoPAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol-choline-phosphotransferase (PAF-CPT) in leukocytes, and lipoprotein-associated phospholipase A2 (LpPLA2) in serum were determined. The quantities of interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP), oxidized LDL (ox-LDL), thiobarbituric acid-reactive substances (TBARS), and glutathione peroxidase (GPx), as well as the serum oxidation, were also determined. Both types of fish exerted similar effects as there were no statistically significant differences between the two interventions except for an elevated PAF-CPT and reduced arachidonic acid (AA) in the red blood cell (RBC) membrane lipids after the EF intake.

A Randomized, Double-Blinded Crossover Trial of Short Versus Conventional Pulse Width Subthalamic Deep Brain Stimulation in Parkinson's Disease.

Background:Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control with a decrease in energy consumption. However, only little is known about the effect of short pulse width stimulation beyond the setting of an acute challenge.Objective:To compare 4 weeks of STN-DBS with conventional pulse width stimulation (60 μs) to 4 weeks of STN-DBS with short pulse width stimulation (30 μs) regarding motor symptom control.Methods:This study was a monocentric, double-blinded, randomized crossover non-inferiority trial investigating whether short pulse width stimulation with 30 μs maintains equal motor control as conventional 60 μs stimulation over a period of 4 weeks (German Clinical Trials Register No. DRKS00017528). Primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life.Results:Due to a high dropout rate, the calculated sample size of 27 patients was not met and 24 patients with Parkinson’s disease and STN-DBS were included in the final analysis. However, there were no differences in any investigated outcome parameter between the two treatment conditions.Conclusion:This study demonstrates that short pulse width settings (30 μs) provide non-inferior motor symptom control as conventional (60 μs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

Levetiracetam in Alzheimer's Disease: Do Epileptologists Already Have the Cure?

Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial Vossel K, Ranasinghe KG, Beagle AJ, et al. JAMA Neurol. 2021;78(11):1345-1354. doi:10.1001/jamaneurol.2021.3310.Importance:Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD).Objective:To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD.Design, setting, and participants:The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination.Interventions:Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence.Main outcomes and measures:The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale—Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity.Results:Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, .07 points; 95% CI, −.18 to .32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, .2–14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = .11; P = .02). There were no treatment discontinuations because of adverse events.Conclusions and relevance:In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD.

Vascular benefits of vitamin C supplementation against fine particulate air pollution in healthy adults: A double-blind randomised crossover trial

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 μg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

Effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in patients with fibromyalgia.

BACKGROUNDFibromyalgia (FM) syndrome is mainly characterized by widespread pain, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting the potential pathogenic role of the gut microbiota (GM). The GM is deeply influenced by several environmental factors, especially the diet, and recent findings highlighted significant symptom improvement in FM patients following various nutritional interventions such as vegetarian diet, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols based diets, gluten-free diet, and especially an ancient grain supplementation. In particular, a recent study reported that a replacement diet with ancient Khorasan wheat led to an overall improvement in symptom severity of FM patients.AIMTo examine the effects of ancient Khorasan wheat on the GM, inflammation, and short-chain fatty acid production in FM patients.METHODSAfter a 2-wk run-in period, 20 FM patients were enrolled in this randomized, double-blind crossover trial. In detail, they were assigned to consume either Khorasan or control wheat products for 8 wk and then, following an 8-wk washout period, crossed. Before and after treatments, GM characterization was performed by 16S rRNA sequencing while the fecal molecular inflammatory response and the short-chain fatty acids (SCFAs) were respectively determined with the Luminex MAGPIX detection system and a mass chromatography-mass spectrometry method.RESULTSThe Khorasan wheat replacement diet, in comparison with the control wheat diet, had more positive effects on intestinal microbiota composition and on both the fecal immune and SCFAs profiles such as the significant increase of butyric acid levels (P = 0.054), candidatus Saccharibacteria (P = 9.95e-06) and Actinobacteria, and the reduction of Enterococcaceae (P = 4.97e-04). Moreover, the improvement of various FM symptoms along with the variation of some gut bacteria after the Khorasan wheat diet have been documented; in fact we reported positive correlations between Actinobacteria and both Tiredness Symptoms Scale (P < 0.001) and Functional Outcome of Sleep Questionnaire (P < 0.05) scores, between Verrucomicrobiae and both Widespread Pain Index (WPI) + Symptom Severity scale (SS) (P < 0.05) and WPI (P < 0.05) scores, between candidatus Saccharibacteria and SS score (P < 0.05), and between Bacteroidales and Sleep-Related and Safety Behaviour Questionnaire score (P < 0.05). CONCLUSIONThe replacement diet based on ancient Khorasan wheat results in beneficial GM compositional and functional modifications that positively correlate with an improvement of FM symptomatology.

Effects of trazodone on behavioral and physiological signs of stress in dogs during veterinary visits: a randomized double-blind placebo-controlled crossover clinical trial.

To determine whether a single dose of trazodone administered to dogs before a veterinary visit reduced their behavioral and physiologic signs of stress and owners' stress during veterinary visits. 20 dogs and their owners. In this randomized double-blinded placebo-controlled crossover clinical trial, dogs with a history of anxiety during veterinary visits were scheduled for 2 veterinary visits 1 week apart and randomly assigned to receive a single oral dose of either trazodone (9 to 12 mg/kg) or a placebo 90 minutes before transport to the veterinary clinic for alternate visits between September 21 and November 3, 2019. For each visit, we collected and assessed owner-completed surveys of dog stress score (DSS) and owner stress score; various investigator-reported scores, including from video-recorded behavior analyses; and patient-related physiologic data. Dogs treated with trazodone versus placebo had lower mean DSSs, assessed by owners for physical examination and assessed by video analysis for time spent in the examination room; lower mean SD of normal-to-normal intervals, root mean square of successive heartbeat interval difference, and respiratory rate; and higher mean heart rate. No meaningful differences were observed in other behavioral or physiologic outcomes, including serum cortisol concentrations. A single dose of trazodone before transport reduced signs of stress during veterinary visits for dogs in the present study and may be useful as an anti-anxiety medication for similarly affected dogs, potentially resulting in higher-quality clinical examinations and improved patient welfare.

Breast cancer survivors’ typhoid vaccine responses: Chemotherapy, obesity, and fitness make a difference

PurposeTo investigate breast cancer survivors’ inflammatory responses to typhoid vaccine as a window into their innate immune response to novel pathogens. MethodsThis double-blind crossover trial randomized 158 breast cancer survivors to either the vaccine/saline placebo or the placebo/vaccine sequence. The relative contributions of age, cardiorespiratory fitness (VO2peak), type of cancer treatment, central obesity, and depression to interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and WBC vaccine responses were assessed pre-injection and 1.5, 3, 4.5, 6, and 7.5 h post-injection. ResultsThe vaccine produced larger IL-6, IL-1Ra, and WBC responses than placebo, ps < 0.0001. Prior chemotherapy, higher central obesity, and lower VO2peak were associated with smaller vaccine responses after controlling for baseline inflammation. Vaccine response was summarized by the percent increase in area under the curve (IL-6, WBC) or average post-injection mean (IL-1Ra) for vaccine relative to placebo. Women who received chemotherapy had smaller vaccine responses than women who did not for both IL-6 (44% vs 78%, p <.001) and WBC (26% vs 40%, p <.001); IL-1ra response was not significantly moderated by chemotherapy. Women whose central adiposity was one standard deviation above the mean had smaller vaccine responses than women with average adiposity for IL-6 (33% vs 54%, p <.001), WBC (20% vs 30%, p <.001), and IL-1Ra (2.0% vs 3.2%, p <.001). Women with an average level of VO2peak had smaller vaccine responses than women whose VO2peak was one standard deviation above the mean for IL-6 (54% vs 73%, p <.001), WBC (30% vs 40%, p <.001), and IL-1Ra (3.2% vs. 4.1%, p = 0.01). Age and depression did not significantly moderate vaccine responses. ConclusionsThis study provided novel data on chemotherapy’s longer-term adverse immune consequences. The data also have an important public health message: even relatively low levels of fitness can benefit the innate immune response to a vaccine.

Short-Term Ingestion of Medium-Chain Triglycerides Could Enhance Postprandial Consumption of Ingested Fat in Individuals with a Body Mass Index from 25 to Less than 30: A Randomized, Placebo-Controlled, Double-Blind Crossover Study.

The elimination of obesity is essential to maintaining good health. Medium-chain triglycerides (MCTs) inhibit fat accumulation. However, studies examining energy expenditure and fat oxidation with continuous ingestion of MCTs show little association with the elimination of obesity. In this study, we conducted a randomized, double-blind crossover clinical trial to investigate the effects of continuous ingestion of MCTs on postprandial energy expenditure and ingested long-chain triglycerides (LCTs) oxidation. A daily 2 g of MCTs were ingested for two weeks by sedentary participants with a body mass index (BMI) from 25 (kg/m2) to less than 30. Ingestion of a meal containing MCTs and isotopic carbon-13-labeled (13C) LCTs increased energy expenditure and consumption of diet-derived LCTs, as determined by postprandial 13C carbon dioxide excretion, compared to canola oil as the placebo control. These results indicate that continuous ingestion of MCTs could enhance postprandial degradation of diet-derived fat and energy expenditure in sedentary, overweight individuals.

Effect of acetazolamide on obstructive sleep apnoea in highlanders: protocol for a randomised, placebo-controlled, double-blinded crossover trial

IntroductionObstructive sleep apnoea (OSA) is a highly prevalent disease that causing systemic hypertension. Furthermore, altitude-dependent hypobaric hypoxic condition and Tibetan ethnicity have been associated with systemic hypertension independent of OSA,...

Differential effects of renin-angiotensine-aldosteron system inhibition, sympathoinhibition and low sodium diet on blood pressure in women with a history of preeclampsia: A double-blind, placebo-controlled cross-over trial (the PALM study)

Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n=10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.

Sensitive inflammatory biomarkers of acute fine particulate matter exposure among healthy young adults: Findings from a randomized, double-blind crossover trial on air filtration

The short-term alteration of peripheral cytokines may be an early adverse health effect of PM2.5 exposure and may be further associated with cardiovascular disease. We conducted a randomized, double-blind crossover trial using true or sham air filtration among 54 healthy college students in Beijing to investigate the potential benefits of short-term indoor air filtration and the adverse health effects of time-weighted personal PM2.5 exposure through inflammatory cytokines. The participants randomly received true or sham air filtration intervention for a week, and the treatment was changed after a two-week washout period. Peripheral blood samples were collected after each intervention period to measure 38 inflammatory cytokines. A linear mixed-effects model was applied to estimate the impacts of air purification or a 10 μg/m3 PM2.5 exposure increase on cytokines. Lag effects of PM2.5 exposure were analyzed using single-day and moving average lag models. Air filtration reduced indoor and time-weighted average personal PM2.5 concentrations by 69.0% (from 33.6 to 10.4 μg/m3) and 40.3% (from 40.6 to 24.3 μg/m3), respectively. We observed a significant association of PM2.5 exposure with growth-regulated alpha protein (GRO-α) of −11.3% (95%CI: 17.0%, −5.4%). In the lag models, significant associations between personal PM2.5 exposure and interleukin-1 receptor antagonist (IL-1Ra), monocyte chemotactic protein (MCP-1), and eotaxin were obtained at lag0, while associations with cytokines including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein-1β (MIP-1β), IL-4, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were noted at relatively long lagged exposure windows (lag5-lag6). No significant alteration in cytokines was observed under true air filtration intervention. Our study indicates the effectiveness of air filtration on indoor PM2.5 reduction. PM2.5 exposure may decrease GRO-α levels and change different cytokine levels time-varyingly. Further study is still needed to explore the mechanisms of PM2.5 exposure on the inflammatory response.

Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson's Disease: Interim Results from a Randomized Double-Blind Clinical Trial.

Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson's disease (PD). We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platformResults:The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st-3rd quartile] of 3.07 [3.12-4.62] cm with sham-DBS, 1.95 [2.29-3.85] cm with PPN-DBS and 2.78 [1.66-4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.

Vitamin B6 Supplementation Reduces Symptoms of Depression in College Women Taking Oral Contraceptives: A Randomized, Double-Blind Crossover Trial

Oral contraceptive (OC) users have a heightened risk of low plasma concentrations of vitamin B6, a cofactor in the tryptophan-serotonin pathway critical to mood regulation. The purpose of this crossover study was to determine whether vitamin B6 supplementation reduced symptoms of depression and improved mood states in college women using OC. Participants were healthy (aged 18–25 yrs), did not take dietary supplements, and used OC (estrogen with progestin) consistently for at least 1 year. During the 12-week, randomized, double-blind crossover trial (4-week treatment periods [100 mg vitamin B6 daily or placebo] separated by a 4-week washout) participants (n = 8) maintained normal exercise and eating patterns and recorded tablet consumption daily. The Beck Depression Inventory-II (BDI-II) and Profile of Mood States (POMS) were used to assess mental health before and after each 4-week treatment period. Average dietary vitamin B6 intakes did not vary during the trial (1.2–1.4 mg/d), whereas vitamin B6 status rose significantly following the B6 supplementation period compared to the other three time points. BDI-II scores were reduced 20% by vitamin B6 supplementation in comparison to an 11% rise with placebo ingestion (p = 0.046). POMS scores were not significantly impacted by vitamin B6 supplementation. These preliminary data support a growing literature suggesting the benefits of B6 supplementation for reducing symptoms of depression in young women using OC.

A randomized double-blind cross-over trial to study the effects of resistant starch prebiotic in chronic kidney disease (ReSPECKD)

BackgroundChronic kidney disease (CKD) is associated with a reduced quality of life and an increased risk of kidney failure, cardiovascular events, and all-cause mortality. Accumulation of nitrogen-based uremic toxins leads to worsening of symptoms in individuals with CKD. Many uremic toxins, such as indoxyl and p-cresol sulphate, are produced exclusively by the gut microbiome through the proteolytic digestion of aromatic amino acids. Strategies to reduce the production of these toxins by the gut microbiome in individuals with CKD may lessen symptom burden and delay the onset of dialysis. One such strategy is to change the overall metabolism of the gut microbiome so that less uremic toxins are produced. This can be accomplished by manipulating the energy source available to the microbiome. Fermentable carbohydrates which reach the gut microbiome, like resistant starch (RS), have been shown to inhibit or reduce bacterial amino acid metabolism. This study aims to investigate the effects of resistant potato starch (RPS) as a prebiotic in individuals with CKD before the onset of dialysis.MethodsThis is a double-blind, randomized two-period crossover trial. Thirty-six eligible participants will consent to follow a 26-week study regimen. Participants will receive 2 sachets per day containing either 15 g of RPS (MSPrebiotic, resistant potato starch treatment) or 15 g cornstarch (Amioca TF, digestible starch control). Changes in blood uremic toxins will be investigated as the primary outcome. Secondary outcomes include the effect of RPS consumption on symptoms, quality of life and abundance, and diversity and functionality of the gut microbiome.DiscussionThis randomized trial will provide further insight into whether the consumption of RPS as a prebiotic will reduce uremic toxins and symptoms in individuals who have CKD.Trial registrationClinicalTrials.govNCT04961164. Registered on 14 July 2021

Effects of Unilateral Stimulation in Parkinson's Disease: A Randomized Double-Blind Crossover Trial.

IntroductionPrevious studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms.MethodsIn this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med–STN+GPi–, (2) Med–STN–GPi+, (3) Med+STN+GPi–, and (4) Med+STN–GPi+.ResultsEight patients had completed 30 trials of assessment. Compared with the preoperative Med– state, in the Med–STN+GPi– condition, the cardinal symptoms in both sides of the body were all improved. In the Med–STN–GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi– state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN–GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med– and Med+ states. No side effects associated with this study were seen.ConclusionsImprovement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.

Effect of low dose nebulized morphine on respiratory function improvement in mustard gas-exposed patients: A double-blind crossover clinical trial study.

Background:Mustard is one of the most destructive chemical gases used in chemical warfare. Several studies showed effectiveness of inhaled morphine as a secondary treatment for the improvement of dyspnea. Therefore, this study aimed at determining the efficacy of low dose inhaled morphine for respiratory function improvement in patients who were exposed to the mustard gas.Methods:This study was designed as a cross-over double-blinded clinical trial. Patients exposed to mustard gas were randomly assigned into two groups: 1) received 0.4 mg of morphine by inhalation and 2) received 5 ml of normal saline serum as a placebo in the same manner. After a washout period of one week, the first group received the placebo and the second group received morphine for 5 days. Spirometric indices, expiratory flow peak, exercise test, severity of dyspnea, and quality of life were evaluated as respiratory function parameters. Data analysis was done using SPSS software Version 16.Results:The mean maximum expiratory flow was significantly higher among cases who used morphine in comparison with the placebo group (p<0.05). Moreover, the severity of dyspnea, quality of life, and the frequency of coughing during the day were significantly improved among the recipients of morphine (p<0.05) while the spirometric indices and exercise tolerance tests were similar between the two groups (p>0.05), but the mean peak expiratory flow (PEFR) was significantly higher among the patients receiving morphine than the placebo patients (p<0.001).Conclusion:The use of inhaled morphine had a significant positive effect on the respiratory system of people exposed to mustard gas. We can use low doses of inhaled morphine to improve the respiratory function of these patients as a secondary therapy.

Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson’s disease

IntroductionAfter several years of brain-sensing technology development and proof-of-concept studies, adaptive deep brain stimulation (aDBS) is ready to better treat Parkinson’s disease (PD) using aDBS-capable implantable pulse generators (IPGs). New...

The second brain in Parkinson's disease: fact or fantasy?

The second brain in Parkinson's disease: fact or fantasy?

Melissa Officinalis and Essential Hypertension

For long plants and herbs have been used to treat cardiovascular diseases and Melissa officinalis (M. officinalis) Is one of those plants. However, there is no conclusive evidence for the effects of the plant on both systolic and diastolic blood pressures in hypertensive patients. Shekarriz and colleagues performed a double-blind cross-over clinical trial with 49 hypertensive patients given either placebo or capsules of the plant (400mg/d) thrice a day for a week. The blood pressure was measured at baseline once and then biweekly for 2.5 months. Their findings revealed that both systolic and diastolic blood pressures were reduced in patients given M. officinalis compared to the placebo. Moreover, no drastic adverse effects were observed. Hence, they conclude that in patients with primary hypertension, both systolic and diastolic blood pressures can be significantly decreased by M. officinalis. Phytother Res. 2021 Dec;35(12):6883-6892.