Validation of the predictive value of BDNF-87 methylation for antidepressant treatment success in severely depressed patients—a randomized rater-blinded trial

Trials

Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression …

During the last 30 years, a large number of behavioral studies have investigated the effect of simultaneous exercise on cognitive functions The heterogeneity of the results has been attributed to different parameters, such as intensity or modality of physical activity, and the investigated cognitive processes. More recent methodological improvements have enabled to record electroencephalography (EEG) during physical exercise. EEG studies combining cognitive tasks with exercise have described predominantly detrimental effects on cognitive processes and EEG parameters. However, differences in the underlying rationale and the design of EEG versus behavioral studies make direct comparisons between both types of studies difficult. In this narrative review of dual-task experiments we evaluated behavioral and EEG studies and discuss possible explanations for the heterogeneity of results and for the discrepancy between behavioral and EEG studies. Furthermore, we provide a proposal for future EEG studies on simultaneous motion to be a useful complement to behavioral studies. A crucial factor might be to find for each cognitive function the motor activity that matches this function in terms of attentional focus. This hypothesis should be investigated systematically in future studies.

Frontiers in Neuroscience

IntroductionAuditory-motor interactions can support the preparation for expected sensory input. We investigated the periodic modulation of beta activity in the electroencephalogram to assess the role of active auditory-motor synchronization. Pre-stimulus beta activity (13–30 Hz) has been interpreted as a neural signature of the preparation for expected sensory input.MethodsIn the current study, participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either rhythmically (at 1 Hz) or arrhythmically with variable intervals. In addition to the pedaling conditions with rhythmic (auditory-motor synchronization, AMS) or arrhythmic stimulation, a self-generated stimulus condition was used in which tones were presented in sync with the participants’ spontaneous pedaling. This condition served to explore whether sensory predictions are driven primarily by the auditory or by the motor system.ResultsPre-stimulus beta power increased for rhythmic compared to arrhythmic stimulus presentation in both sitting and pedaling conditions but was strongest in the AMS condition. Furthermore, beta power in the AMS condition correlated with motor performance, i.e., the better participants synchronized with the rhythmic stimulus sequence, the higher was pre-stimulus beta power. Additionally, beta power was increased for the self-generated stimulus condition compared with arrhythmic pedaling, but there was no difference between the self-generated and the AMS condition.DiscussionThe current data pattern indicates that pre-stimulus …

Trials

Background Benefits to patients from reduced depression have been shown from monitoring progress with patient-reported outcome measures (PROMs) in psychological therapy and mental health settings. This approach has not yet been researched in the United Kingdom for primary care, which is where most people with depression are treated in the United Kingdom. Methods This is a parallel-group cluster randomised trial with 1:1 allocation to intervention and control. Patients who are age 18+ years, with a new episode of depressive disorder/symptoms, meet the inclusion criteria. Patients with current depression treatment, comorbid dementia/psychosis/substance misuse/suicidal ideas are excluded. The intervention includes the Administration of Patient Health Questionnaire (PHQ-9) as a PROM within 2 weeks of diagnosis and at follow-up 4 weeks later. General practitioners are trained in interpreting scores …

Trials

BackgroundKeloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids.MethodsIn this randomised clinical trial, 46 adults with keloids were divided into two treatment groups …

Trials

ObjectivesEstablishment of effective evidence-based interventions in rehabilitation of working memory (WM) deficits after acquired brain injury (ABI) is sorely needed. Despite robust evidence for the efficiency of clinical hypnosis in a wide range of clinical conditions, and improved understanding of mechanisms underlying its effects, the potential of clinical hypnosis in cognitive rehabilitation is underexplored. A recent study has shown large effects of hypnotic suggestion on WM capacity following ABI. This randomized controlled trial aims to evaluate and explore the replicability of these findings and examine the generalization of treatment effects. The study will also explore possible mechanisms of change.MethodsNinety patients will be recruited from the Sunnaas Rehabilitation Hospital. Inclusion criteria are nonprogressive ABI, minimum 12-month post-injury, ongoing WM deficits, and age between 18 and 67 years …

Trials

BackgroundCystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins.MethodsThis prospective, single-blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble …

Trials

BackgroundApproximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs).MethodsWe will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom …

Trials

BackgroundApproximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs).MethodsWe will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom …

Trials

BackgroundDespite the critical importance of clinical trials to provide evidence about the effects of intervention for children and youth, a paucity of published high-quality pediatric clinical trials persists. Sub-optimal reporting of key trial elements necessary to critically appraise and synthesize findings is prevalent. To harmonize and provide guidance for reporting in pediatric controlled clinical trial protocols and reports, reporting guideline extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines specific to pediatrics are being developed: SPIRIT-Children (SPIRIT-C) and CONSORT-Children (CONSORT-C).MethodsThe development of SPIRIT-C/CONSORT-C will be informed by the Enhancing the Quality and Transparency of Health Research Quality (EQUATOR) method for reporting guideline development in …

Trials

BackgroundIndigenous youth in Northwestern Ontario who need mental health supports experience longer waits than non-Indigenous youth within the region and when compared to youth in urban areas. Limited access and extended waits can exacerbate symptoms, prolong distress, and increase risk for adverse outcomes. Innovative approaches are urgently needed to provide support for Indigenous youth in Northwestern Ontario. Using a randomized controlled trial design, the primary objective of this study is to determine the effectiveness of the JoyPop app compared to usual practice (UP; monitoring) in improving emotion regulation among Indigenous youth (12–17 years) who are awaiting mental health services. The secondary objectives are to (1) assess change in mental health difficulties and treatment readiness between youth in each condition to better understand the app’s broader impact as a waitlist tool …

Trials

Background Benefits to patients from reduced depression have been shown from monitoring progress with patient-reported outcome measures (PROMs) in psychological therapy and mental health settings. This approach has not yet been researched in the United Kingdom for primary care, which is where most people with depression are treated in the United Kingdom. Methods This is a parallel-group cluster randomised trial with 1:1 allocation to intervention and control. Patients who are age 18+ years, with a new episode of depressive disorder/symptoms, meet the inclusion criteria. Patients with current depression treatment, comorbid dementia/psychosis/substance misuse/suicidal ideas are excluded. The intervention includes the Administration of Patient Health Questionnaire (PHQ-9) as a PROM within 2 weeks of diagnosis and at follow-up 4 weeks later. General practitioners are trained in interpreting scores …

Trials

Correction: Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III) - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now. Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Trials v.25; 2024 PMC10941458 Other Formats PDF (623K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Trials v.25; 2024 PMC10941458 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply …

Trials

BackgroundAdolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology.MethodsA cluster randomised allocation design is adopted with randomisation at the school year …

Trials

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.MethodsThe HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is …

Trials

BackgroundThe World Health Organization recommends universal iron supplementation for children aged 6–23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation.MethodsThis will be a two-arm, randomised controlled trial. Gambian children aged 6–12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 …

Trials

BackgroundLiver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).Methods/designThe BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis …

Trials

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and …

Trials

BackgroundOccupational Therapists use craft-making activities as therapeutic interventions to improve physical and psychological functioning of injured people. Despite the therapeutic effects, craft-making is not routinely used in hand rehabilitation as an intervention for patients with upper limb fractures. These patients often experience physical and psychosocial issues; however, without supportive evidence, therapists hesitate to integrate craft-making into upper limb rehabilitation.PurposeThis study aims to determine the effect of a conventional therapy combined with therapeutic craft-making on disability, post-traumatic stress, and physical performance in patients with lower-third forearm fractures.MethodsPriori analysis determined that 38 patients will be needed for this superiority randomized controlled trial to be conducted in a hand and upper limb rehabilitation center. Eligible participants must comprehend …

Trials

BackgroundOver 3000 young people under the age of 18 are admitted to Tier 4 Child and Adolescent Mental Health Services (CAMHS) inpatient units across the UK each year. The average length of hospital stay for young people across all psychiatric units in the UK is 120 days. Research is needed to identify the most effective and efficient ways to care for young people (YP) with psychiatric emergencies. This study aims to evaluate the clinical effectiveness and cost-effectiveness of intensive community care service (ICCS) compared to treatment as usual (TAU) for young people with psychiatric emergencies.MethodsThis is a multicentre two-arm randomized controlled trial (RCT) with an internal pilot phase. Young people aged 12 to < 18 considered for admission at participating NHS organizations across the UK will be randomized 1:1 to either TAU or ICCS. The primary outcome is the time to return to or start …

Trials

Digital interventions offer many possibilities for improving health, as remote interventions can enhance reach and access to underserved groups of society. However, research evaluating digital health interventions demonstrates that such technologies do not equally benefit all and that some in fact seem to reinforce a “digital health divide.” By better understanding these potential pitfalls, we may contribute to narrowing the digital divide in health promotion. The aim of this article is to highlight and reflect upon study design decisions that might unintentionally enhance inequities across key research stages—recruitment, enrollment, engagement, efficacy/effectiveness, and retention. To address the concerns highlighted, we propose strategies including (1) the standard definition of “effectiveness” should be revised to include a measure of inclusivity; (2) studies should report a broad range of potential inequity indicators of …

Trials

BackgroundWithin England, children and young people (CYP) who come into police custody are referred to Liaison and Diversion (L&D) teams. L&D teams have responsibility for liaising with healthcare and other support services while working to divert CYP away from the criminal justice system but have traditionally not provided targeted psychological interventions to CYP. Considering evidence that Solution Focused Brief Therapy (SFBT) leads to a reduction in internalising and externalising behaviour problems in CYP, the aim of this randomised controlled trial (RCT) was to determine whether there is a difference between services as usual (SAU) plus SFBT offered by trained therapists working within a L&D team, and SAU alone, in reducing offending behaviours in 10–17-year-olds presenting at police custody.MethodsDesign: two-arm individually RCT with internal pilot and process evaluation.Participants: N …

Trials

BackgroundDepression continues to be an ongoing threat to adolescent well-being with Black adolescents being particularly vulnerable to greater burdens of depression as well as lower mental health service utilization. Black adolescents are likely to have untreated depression due to social network influences, varied perceptions of services and providers, or self-stigma associated with experiencing depressive symptoms. Furthermore, if or when treatment is initiated, low engagement and early termination are common. To address this gap, a trial is being conducted to preliminarily test the effectiveness of an engagement intervention targeting Black adolescents with depression in school mental health services in New York City.MethodsA total of 60 Black middle and high school adolescents displaying depressive symptoms are equally randomized (based on school site) to the treatment arms. Both trial arms deliver …