Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM’Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial

Abstract Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

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Transcranial Random Noise Stimulation Does Not Enhance the Effects of Working Memory Training

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00993 ◽

2016 ◽

Vol 28 (10) ◽

pp. 1471-1483 ◽

Cited By ~ 5

Author(s):

Joni Holmes ◽

Elizabeth M. Byrne ◽

Susan E. Gathercole ◽

Michael P. Ewbank

Keyword(s):

Working Memory ◽

Cognitive Abilities ◽

Controlled Trial ◽

Random Noise ◽

Working Memory Training ◽

Memory Training ◽

Double Blind ◽

Transcranial Random Noise Stimulation ◽

Therapeutic Value ◽

First Time

Transcranial random noise stimulation (tRNS), a noninvasive brain stimulation technique, enhances the generalization and sustainability of gains following mathematical training. Here it is combined for the first time with working memory training in a double-blind randomized controlled trial. Adults completed 10 sessions of Cogmed Working Memory Training with either active tRNS or sham stimulation applied bilaterally to dorsolateral pFC. Training was associated with gains on both the training tasks and on untrained tests of working memory that shared overlapping processes with the training tasks, but not with improvements on working memory tasks with distinct processing demands or tests of other cognitive abilities (e.g., IQ, maths). There was no evidence that tRNS increased the magnitude or transfer of these gains. Thus, combining tRNS with Cogmed Working Memory Training provides no additional therapeutic value.

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Transcranial Electric And Acoustic Stimulation For Tinnitus: Study Protocol For A Randomized Double-Blind Controlled Trial Assessing The Influence of Combined Transcranial Random Noise And Acoustic Stimulation On Tinnitus Loudness And Distress

10.21203/rs.3.rs-637175/v1 ◽

2021 ◽

Author(s):

Mariana Lopes Martins ◽

Tobias Kleinjung ◽

Martin Meyer ◽

Vitushika Raveenthiran ◽

Zino Wellauer ◽

...

Keyword(s):

Outcome Measures ◽

Neuronal Activity ◽

Treatment Option ◽

Brain Activity ◽

Controlled Trial ◽

Random Noise ◽

Acoustic Stimulation ◽

Secondary Outcome ◽

Double Blind ◽

Transcranial Random Noise Stimulation

Abstract Background: Tinnitus is the result of aberrant neuronal activity. As a novel treatment form, neuromodulation is used to modify neuronal activity of brain areas involved in tinnitus generation. Among the different forms of electric stimulation, transcranial Random Noise Stimulation (tRNS) has been shown to be a promising treatment option for tinnitus. In addition, recent studies indicate that the reduction in tinnitus can be more pronounced when different modalities of stimulation techniques are combined (“bimodal stimulation”). TRNS can be used in combination with acoustic stimulation (AS), a further treatment option recognized in the literature. The aim of the proposed study is to investigate whether simultaneous tRNS and AS improve levels of tinnitus loudness and distress. Methods: The intervention consists of bilateral HD-tRNS over the auditory cortex combined with the application of AS which is studied in a cross-over design. The visits will be performed in 26 sessions. There will be 20 treatment sessions, divided into two blocks: active and sham HD-tRNS. Within the blocks, the interventions are divided into Group A: HD-tRNS and AS, and Group B: HD-tRNS alone. Furthermore, in addition to the assessments directly following the intervention sessions, there will be six extra sessions performed subsequently at the end of each block, after a period of some days (Follow-ups 1 and 2) and a month after the last intervention (C). Primary outcome measures are analogue scales for evaluation of subjective tinnitus loudness and distress, and the audiological measurement of Minimum Masking Level (MML). Secondary outcome measures are brain activity as measured by electroencephalography and standardized questionnaires for evaluating tinnitus distress and severity. Discussion: To the best of our knowledge, this is the first study, which uses HD-tRNS combined with AS for tinnitus treatment. The cross-over design permits the comparison between HD-tRNS active vs. sham and with vs. without AS. Thus, it will be possible to evaluate the efficacy of the combined approach to HD-tRNS alone. In addition, the use of different objective and subjective evaluations for tinnitus enable more reliable and valid results. Trial registration: Swiss Ethics Committee (BASEC-Nr. 2020-02027); Swiss Federal Complementary Database (kofam.ch: SNCTP000004051); and ClinicalTrials.gov (clinicaltrials.gov: NCT04551404).

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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Effect of antenatal dietary myo-inositol supplementation on the incidence of gestational diabetes mellitus and fetal outcome: protocol for a double-blind randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2021-055314 ◽

2022 ◽

Vol 12 (1) ◽

pp. e055314

Author(s):

Ibrahim Ibrahim ◽

Hala Abdullahi ◽

Yassin Fagier ◽

Osman Ortashi ◽

Annalisa Terrangera ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Controlled Trial ◽

Tolerance Test ◽

Dietary Advice ◽

Controlled Clinical Trial ◽

Oral Glucose ◽

Double Blind ◽

Registration Number

IntroductionGestational diabetes mellitus (GDM) affects 23.6% of Qatari women and is associated with maternal and perinatal morbidity and long-term risk of developing type 2 diabetes. A number of challenges exist with current interventions, including non-compliance with dietary advice, the reluctance of mothers to ingest metformin tablets or use insulin injections. These challenges highlight the importance of pursuing evidence-based prevention strategies. Myo-inositol is readily available as an US Food and Drug Administration-approved food supplement with emerging but limited evidence suggesting it may be beneficial in reducing the incidence of GDM. Further studies, such as this one, from different ethnic contexts and with differing risk factors, are urgently needed to assess myo-inositol effects on maternal and neonatal outcomes.Methods and analysisThis study is a prospective, randomised, double-blinded, placebo controlled clinical trial to either myo-inositol supplementation or placebo.We plan to enrol 640 pregnant women attending antenatal care at Sidra Medicine, Doha, Qatar, 320 in each arm. All participants will complete at least 12 weeks of supplementation prior to undertaking the Oral Glucose Tolerance Test at 24–28 weeks. The daily use of the trial supplementation will continue until the end of pregnancy. All outcome measures will be collected from the electronic medical records.Ethics and disseminationEthical approval for the study was obtained on 12 April 2021 from Sidra Medicine (IRB number 1538656). Results of the primary trial outcome and secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberProspectively registered on 26 May 2021. Registration number ISRCTN16448440 (ISRCTN registry).

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Treament and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial

Cadernos de Saúde Pública ◽

10.1590/s0102-311x2008001400011 ◽

2008 ◽

Vol 24 (suppl 2) ◽

pp. s259-s271 ◽

Cited By ~ 8

Author(s):

Maria Claret Costa Monteiro Hadler ◽

Dirce Maria Sigulem ◽

Maria de Fátima Costa Alves ◽

Vinícius Montenegro Torres

Keyword(s):

Folic Acid ◽

Ferrous Sulfate ◽

Controlled Trial ◽

Acid Group ◽

Hemoglobin Level ◽

Controlled Clinical Trial ◽

Double Blind ◽

Treatment Groups ◽

Daycare Centers ◽

Randomized Controlled

The objective of this study was to assess the prevalence of anemia and the therapeutic and prophylactic response to ferrous sulfate and folic acid. A double-blind, randomized, controlled clinical trial was conducted with 196 children 6 to 24 months of age enrolled in municipal daycare centers in Goiânia, Goiás State, Brazil. The children were assigned to two treatment groups that received a daily dose (5 times a week) of either 4.2mg/kg/day of ferrous sulfate + folic acid (50µg) or 4.2mg/kg/day of ferrous sulfate + folic acid placebo. One of the prevention groups received 1.4mg/kg/day of ferrous sulfate + folic acid (50µg/day) and the other 1.4mg/kg/day of ferrous sulfate + folic acid placebo. Supplementation lasted approximately three months. Baseline anemia prevalence was 56.1% (95%CI: 48.9-63.1). After treatment, anemia prevalence in the folic acid group (14%) was lower than in the placebo group (34.9%) (p = 0.02). After prophylaxis in the non-anemic children, the incidence of anemia did not differ between the groups, but there was an increase in hemoglobin level in the folic acid group (p = 0.003). Iron plus folic acid was effective for the treatment of anemia and improvement of hemoglobin level in non-anemic children.

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Comparison of pharmacokinetics of omega-3 fatty acid supplements in monoacylglycerol or ethyl ester in humans: a randomized controlled trial

European Journal of Clinical Nutrition ◽

10.1038/s41430-020-00767-4 ◽

2020 ◽

Author(s):

Laurie Chevalier ◽

Mélanie Plourde

Keyword(s):

Plasma Concentration ◽

Ethyl Ester ◽

Controlled Trial ◽

Plasma Concentrations ◽

Controlled Clinical Trial ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Post Dose ◽

Double Blind ◽

Omega 3 Fatty Acid

Abstract Background A diet low in omega-3 fatty acids (n-3 FA) results in low plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main long chain n-3 FA. n-3 FA supplements on the market are esterified in triglycerides (TG) or ethyl ester (EE); the latter is absorbed less than other esterification forms. The objective of this study was to test and compare the pharmacokinetics of n-3 FA esterified in monoacylglycerides (MAG), a predigested form, with the EE form. Methods This study was a randomized, double-blind, crossover, controlled, clinical trial. Ten men and ten women between 18 and 60 years old were recruited. Participants received a single oral dose of 3 g of n-3 FA esterified in EE or MAG. Eleven blood samples were collected over 24 h post-dose. Plasma total lipids were extracted, methylated, and analyzed using gas chromatography. Results After receiving the MAG form, plasma EPA and DHA peaked at a concentration 3 and 2.5 times higher, respectively, than with the EE form. When provided in MAG form, n-3 FA plasma concentration during the absorption phase was on average 3–5 times higher than in EE form. When n-3 FAs were provided esterified in MAG, their concentration 24 h post-dose was higher than in EE. Males had a lower n-3 FA plasma concentration than females when n-3 FAs were provided in EE but there was no sexe difference when provided in MAG. Conclusions Plasma concentration of DHA and EPA was higher when provided in MAG than EE form.

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Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa094 ◽

2020 ◽

Vol 4 (11) ◽

Cited By ~ 1

Author(s):

Giulio R Romeo ◽

Junhee Lee ◽

Christopher M Mulla ◽

Youngmin Noh ◽

Casey Holden ◽

...

Keyword(s):

Glucose Tolerance ◽

Controlled Trial ◽

Area Under The Curve ◽

Cost Effective ◽

Tolerance Test ◽

Controlled Clinical Trial ◽

Oral Glucose ◽

Serious Adverse Events ◽

Double Blind ◽

Favorable Safety

Abstract Context The identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes. Objective The objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes. Design, Setting, Participants, and Intervention This double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks. Main Outcome Measures Primary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT. Results From a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P < .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P < .001) and of the 2-hour PG of the OGTT (P < .05). There were no serious adverse events in either study group. Conclusions In individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.

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Suboptimal Engagement of High-Level Cortical Regions Predicts Random-Noise-Related Gains in Sustained Attention

Psychological Science ◽

10.1177/0956797619856658 ◽

2019 ◽

Vol 30 (9) ◽

pp. 1318-1332 ◽

Cited By ~ 7

Author(s):

Siobhán Harty ◽

Roi Cohen Kadosh

Keyword(s):

Sustained Attention ◽

Random Noise ◽

Explanatory Power ◽

Psychological Research ◽

Cognitive Outcomes ◽

Double Blind ◽

Attention Task ◽

Transcranial Random Noise Stimulation ◽

Cortical Regions ◽

High Level

Interindividual variability in outcomes across individuals poses great challenges for the application of noninvasive brain stimulation in psychological research. Here, we examined how the effects of high-frequency transcranial random-noise stimulation (tRNS) on sustained attention varied as a function of a well-studied electrocortical marker: spontaneous theta:beta ratio. Seventy-two participants received sham, 1-mA, and 2-mA tRNS in a double-blind, crossover manner while they performed a sustained-attention task. Receiving 1-mA tRNS was associated with improved sustained attention, whereas the effect of 2-mA tRNS was similar to the effect of sham tRNS. Furthermore, individuals’ baseline theta:beta ratio moderated the effects of 1-mA tRNS and provided explanatory power beyond baseline behavioral performance. The tRNS-related effects on sustained attention were also accompanied by reductions in theta:beta ratio. These findings impart novel insights into mechanisms underlying tRNS effects and emphasize how designing studies that link variability in cognitive outcomes to variability in neurophysiology can improve inferential power in neurocognitive research.

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Pramipexole in peritoneal dialysis patients with restless legs syndrome (RLS): a protocol for a multicentre double-blind randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2019-033815 ◽

2020 ◽

Vol 10 (2) ◽

pp. e033815

Author(s):

Tian-tian Ma ◽

Zhikai Yang ◽

Sainan Zhu ◽

Jing-hong Zhao ◽

Yi Li ◽

...

Keyword(s):

Clinical Trial ◽

Peritoneal Dialysis ◽

Restless Legs Syndrome ◽

Rating Scale ◽

Controlled Trial ◽

Psychological Status ◽

Controlled Clinical Trial ◽

Double Blind ◽

Restless Legs ◽

Peking University

IntroductionRestless legs syndrome (RLS) is a common neurological sensorimotor disorder among patients with end stage renal disease. This clinical trial aimed to provide evidence on the efficacy and safety of pramipexole in patients with uremic RLS receiving peritoneal dialysis (PD).Methods and analysisThis is a 12-week, multicentre, randomised, double-blind, placebo-controlled clinical trial. In total, 104 patients with uremic RLS receiving PD will be enrolled from four hospitals and randomly assigned in a 1:1 ratio to either placebo or pramipexole. We will determine the efficacy of pramipexole in the improvement of International RLS Study Group Rating Scale as the primary outcome, while responder rates for other RLS scales at week 12, change from baseline to week 12 for psychological status, sleep disorder and quality of life and blood pressure represent the secondary outcomes.Ethics and disseminationThe study was approved by the ethics committees of Peking University First Hospital, Xinqiao hospital of Army Medical University, Cangzhou Center Hospital and Peking University Shenzhen Hospital. The results will be disseminated in peer-reviewed journals.Trial registration numberNCT03817554

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Dexamethasone for Morbidity After Subdural Electrode Insertion – A Randomized Controlled Trial

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710000305x ◽

2003 ◽

Vol 30 (4) ◽

pp. 340-348 ◽

Cited By ~ 14

Author(s):

Ramesh L. Sahjpaul ◽

Jeff Mahon ◽

Samuel Wiebe

Keyword(s):

Pain Relief ◽

Postoperative Period ◽

Controlled Trial ◽

Intractable Epilepsy ◽

Controlled Clinical Trial ◽

Antiemetic Drug ◽

Double Blind ◽

Dexamethasone Group ◽

Significant Difference ◽

Limited Duration

Background:Invasive monitoring with subdural electrodes (SDE) for investigation of medically intractable epilepsy may be associated with undesirable immediate postoperative morbidity such as headache, nausea, vomiting, fever, and meningism. We undertook to evaluate the potential beneficial role of perioperative dexamethasone in reducing these symptoms.Methods:In a double-blind placebo controlled clinical trial 30 patients undergoing SDE insertion were randomized to receive either placebo or a course of dexamethasone beginning one hour prior to surgery and tapering to discontinue over 72 hours postoperatively. Pain, pain relief, nausea, nausea relief, temperature, and meningism were assessed regularly in the postoperative period, and analgesic, antipyretic, and antiemetic drug requirements were tabulated.Results:One patient was withdrawn from the dexamethasone group due to lack of data. With regards to postoperative pain, the direction of benefit favoured dexamethasone but a significant treatment by time interaction prevented further analysis of treatment effect. The dexamethasone group did have significantly lower temperatures and higher nausea relief scores. There was no statistically significant difference between the groups with regards to pain relief, nausea, and meningism scores. The beneficial effects of dexamethasone were delayed in onset, of limited duration, and not uniform over the observation period.Conclusion:Dexamethasone appears to have a role in reducing immediate morbidity following SDE insertion but its effect is not uniform in the postoperative period; it appears to be delayed in onset, and of limited duration. Further study is necessary to determine the ideal dosing schedule.

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