Clinical Research Directory

Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)

Fibromyalgia is characterized by widespread pain, fatigue, non-restorative sleep, and psychocognitive alterations, compromising quality of life and leading to absenteeism and early retirement. Up to 70% of patients discontinue treatment with antidepressants and anticonvulsants due to adverse effects or low efficacy, and more than 30% resort to opioid use. Given the treatment challenges and the scarcity of safe alternatives, there is growing interest in interventions such as transcranial direct current stimulation (tDCS), which has shown efficacy in improving symptoms and functionality, with low cost and few side effects. In this context, we designed a randomized, double-blind, double-dummy clinical trial to compare the non-inferiority of 28 home-based anodal tDCS (2 mA) applied over the primary motor cortex (M1) versus duloxetine 60 mg. Both treatments will be combined with physical exercise and pain education. Outcomes will be assessed through multidimensional measures of pain, functionality, global impression of improvement, and the function of the descending pain inhibitory system. Secondary outcomes include quality of life, depressive symptoms, psychophysical pain measures, and treatment adherence. An additional analysis will compare the results of sham tDCS and duloxetine placebo within the non-inferiority model. Predictors of treatment response will also be explored, including symptom severity and oscillatory patterns of cortical electrical activity, rest-activity rhythm, and autonomic function assessed by R-R interval. Furthermore, serum levels of S100-B protein, brain-derived neurotrophic factor (BDNF), and genetic variants related to neuroplasticity in the BDNF Val66Met, Catechol-O-Methyltransferase (COMT) (rs4680) (G\>A), OPRM1, and PER2 genes will be analyzed. Inflammatory markers (TNF-α, IL-1, IL-2, IL-6, IL-10, C-reactive protein) and serum endorphins will also be assessed. A total of 610 women with fibromyalgia (aged 18 to 75 years) will be randomized into three groups (2:2:1): duloxetine + sham tDCS (n=244); active tDCS + placebo (n=244); and sham tDCS + placebo (n=122). Participants will be assessed during treatment and at 3, 6, and 12 months after completing the intervention protocol. An interim analysis will be conducted when \~50% of participants (n ≈ 305) complete the 3-month follow-up by an independent, blinded Data Monitoring Committee (DMC). (i) The trial may be stopped if the conditional probability of demonstrating non-inferiority is \<10%, based on frequentist or Bayesian methods. (i) The trial will be stopped if serious adverse events (SAEs) in the active tDCS group increase by ≥30% compared to duloxetine (p \< 0.01, adjusted). (ii) Early stopping for efficacy will be considered if active tDCS demonstrates clear non-inferiority or superiority over duloxetine on the primary outcome. Superiority requires: (iii) a clinically relevant difference exceeding the non-inferiority margin (≥10% pain reduction); (ii) statistical significance (p \< 0.005, O'Brien-Fleming adjusted); and (iii) a ≥2-point (20%) improvement on the BPI, confirmed in the ITT analysis. This study aims to generate evidence to support the decision-making process of the National Committee for Health Technology Incorporation (CONITEC) regarding the availability of tDCS in the Brazilian Unified Health System (SUS). In addition, identifying predictors of response to tDCS and duloxetine, through the integration of genetic, neurophysiological, inflammatory, and psychosocial markers using machine learning algorithms, will allow for identifying factors that can personalize fibromyalgia treatment. This approach enhances clinical efficacy, reduces costs associated with ineffective interventions, and supports more accurate therapeutic decisions, expanding access to safe, effective, and sustainable care within the public healthcare system

Impact of Nut Consumption on Mental Health in Young Adults

Nuts have a high nutrient density, and numerous studies have reported their cardiometabolic benefits. Although observational studies in adults have indicated a potential link between nut consumption and improved mental health, there is still insufficient evidence from experimental studies to draw firm conclusions about this association.

The Acute Effect of Different Resistance Exercise Loads on Irisin and Brain-derived Neurotrophic Factor in Blood Serum and Plasma

The aim of this study is to investigate different resistance training loads on BNDF and irisin levels in platelets, blood serum and plasma.

Investigating the Evolutionary Impact of Metabolic Flexibility on Physical Activity-Dependent BDNF and Cognition: Insights From the Val66Met Polymorphism

The goal of this clinical trial is to learn if a state of ketosis and physical activity will increase serum BDNF concentrations and improve cognition, specifically in individuals who possess the Met allele from the BDNF Val66Met SNP. The main questions it aims to answer are: * Does the combination of ketosis and physical activity increase serum BDNF concentrations and cognition? * Do Met Carriers of the BDNF Val66Met SNP demonstrate a significantly larger change in serum BDNF after physical activity and a state of ketosis compared to Val/Val Homozygotes? * Do Met Carriers of the BDNF Val66Met SNP demonstrate a significantly larger increase in cognition after physical activity and a state of ketosis compared to Val/Val Homozygotes? Researchers will compare a ketosis supplement to a placebo (a look-alike substance that contains no drug) to see if the ketosis supplement and physical activity increases serum BDNF and improves cognition. Participants will: * Participate in a drug trial where they will be given the ketosis supplement, and a placebo trial where they will ingest a placebo. * Participants will donate a whole blood sample and take a cognitive test before and after the ketosis and placebo trial. * Participants will take a 30-minute treadmill test during both the ketosis and placebo trial, after ingesting either the drug or placebo for each respective trial.

BDNF Levels in Cancer Patients Receiving Chemotherapy

Cognitive impairment following chemotherapy is defined as chemotherapy-induced cognitive impairment (CCIID). CCIID, which significantly reduces the quality of life of cancer patients receiving chemotherapy, develops as a result of neurotoxicity. It is stated that 75% of patients receiving chemotherapy have cognitive changes. In addition, 35% of patients complain of various cognitive impairments (hearing, perception, decision-making, etc.) for a few months after chemotherapy ends. This situation makes life conditions very difficult for patients who are already experiencing a very difficult disease and treatment process. Brain-Derived Neurotrophic Factor (BDNF) is an extracellular signaling protein known for its dominant role in the development of the nervous system, such as neurogenesis, neuroprotection, neurodegeneration, synaptic plasticity, and resistance to neuronal stress. This protein has opposing effects with its mature form, pro-BDNF protein, and pro-BDNF/BDNF ratios affect neuronal health. Although a number of factors have been identified that are responsible for the deterioration of the cognitive levels of patients receiving chemotherapy, the role of BDNF and pro-BDNF levels in cognitive functions in cancer patients receiving chemotherapy is unknown. In light of this information, the aim of our study is to reveal the effects of chemotherapy-induced cognitive impairment (CIID) on pro-BDNF/BDNF levels and to evaluate the cognitive effects. In line with this aim, patients who apply to Çanakkale Onsekiz Mart University, Faculty of Medicine, Department of Oncology, Polyclinic and Chemotherapy Unit and who have not yet received their first chemotherapy will be included in the study. Before the first chemotherapy, during routine follow-ups in the 3rd month of chemotherapy and in the 6th month in Aydın, 1 extra tube of blood will be taken and BDNF levels will be examined. At the same time, the Montreal Cognitive Assessment (MoCA) test will be applied to the patients to evaluate their cognitive functions. Thus, serum BNDF, proBDNF levels will be determined and the BDNF/proBDNF ratio will be revealed.