Synaptic Regulation Impairment

Researchers are evaluating the safety and effectiveness of NT 201, a type of botulinum toxin A, compared with a placebo in adults who have moderate to severe platysma prominence, which refers to noticeable bands in the neck area. This Phase 3 study aims to understand how well NT 201 works and how safe it is for these participants. The study is sponsored by Merz Aesthetics GmbH and will be conducted in Europe. Participants will be randomly assigned to receive either a single injection of NT 201 or a matching placebo injection in the main study period (MP) on Day 1. After this period, those who received NT 201 can enter an open-label extension period (OLEX) where they will receive another injection of NT 201 on Day 1 of that phase. The study involves a double-blind design, meaning neither the participants nor the researchers know who receives the active drug or placebo during the main period. During the study, participants will be assessed using the Merz Aesthetics Platysma Scale - Dynamic (MAPS-D) to measure improvement in platysma prominence at various time points, including Week 2 and up to Week 17 in the main period. Both investigator and participant assessments will be used to evaluate the degree of improvement. Satisfaction questionnaires and global aesthetic improvement scales will also be used to measure participant satisfaction and aesthetic changes. Safety and efficacy will be closely monitored throughout the study, which lasts through the main and extension periods.

Researchers are studying an experimental therapy to help people recover arm movement after a stroke. This therapy combines functional electrical stimulation with a P-300 based Brain-Computer Interface system (BCI-FES) to assist arm rehabilitation. The study compares two groups: one receives only conventional physical therapy, and the other receives both conventional therapy and BCI-FES. The goal is to improve motor recovery and independence in patients with moderate to severe upper limb weakness due to stroke. Both groups will undergo 20 sessions of conventional physical therapy over 4 weeks, with five sessions each week. The experimental group will also receive 20 sessions of BCI-FES therapy during the same period. The BCI system detects the patient's intended hand movements and assists with movements such as hand opening, grasping, pinching, pronation, and supination. These movements are practiced alongside daily tasks using objects like bottles and spoons. The therapy aims to stimulate brain pathways involved in movement to support recovery. Participants will be evaluated before and after the 4-week treatment using tests that measure arm motor function, spasticity, independence, and depression. Brain imaging with MRI and EEG will assess changes in brain structure and activity. Safety and comfort during sessions will be monitored, including fatigue and skin irritation. The total involvement lasts about one month, with close follow-up during therapy and assessments of progress and brain changes.

Researchers are investigating how mechanical and non-mechanical factors contribute to chronic neck, shoulder, arm, and back pain in full-busted women. This study focuses on women with larger bra cup sizes, exploring how sex hormones, inflammation, and brain changes affect pain. The project aims to fill gaps in understanding pain mechanisms in women with chronic musculoskeletal pain related to breast size. The study evaluates a mechanical intervention using specially designed sports bras for full-busted women (cup sizes D to I) to see if they help reduce pain. Participants in the intervention group will receive one of two types of interventional sports bras to wear for three months. A control group of women with smaller cup sizes (A to C) will be observed without receiving the intervention. Both groups will undergo various baseline and follow-up assessments over three months. Participants will complete online and in-person sessions including questionnaires, pain assessments, body measurements, blood tests, and brain imaging at the start and after three months. Physical activity will be monitored using a smartwatch during the study period. Researchers will collect multiple measures to understand pain, activity, hormone levels, inflammation, biomechanics, and brain activity. The study lasts at least three months, with detailed follow-up to assess the impact of the sports bras and related pain pathways.

Researchers are investigating why some adolescents with depression and suicidal thoughts or behaviors act more impulsively when experiencing negative emotions, a trait called negative urgency. This study focuses on how negative urgency relates to communication between brain cells, particularly through a process called cortical inhibition. The project aims to understand differences in brain signaling between adolescents with suicidal thoughts and those with suicidal behaviors, and how these patterns change over time. Participants aged 13 to 21 years diagnosed with depression and either suicidal ideation or suicidal behavior will be enrolled. Both groups will undergo assessments at the start of the study, and again at 6 and 12 months. These include interviews, questionnaires about emotions and impulsive behavior, computerized brain function tests, MRI brain scans, and measurements of brain cell communication using single-/paired-pulse transcranial magnetic stimulation combined with electroencephalography (TMS-EEG). During the study, adolescents will complete clinical interviews, rating scales, and self-report questionnaires about negative urgency. Brain activity will be measured using TMS-EEG at each visit. Researchers will track changes in brain inhibition and impulsivity over the year to better understand the neural mechanisms behind suicidal behavior. Safety and changes in mental health symptoms will also be monitored throughout the study period.

Researchers are studying how aerobic endurance training affects patients with schizophrenia, focusing on changes in the brain's hippocampus, symptoms, cognition, and daily functioning. The study aims to understand genetic and epigenetic factors influencing brain plasticity after three months of endurance training compared to a control group performing flexibility, strengthening, and balance exercises. The main goal is to examine how a genetic risk score for schizophrenia relates to volume changes in a specific hippocampal region called CA4/DG. Participants are randomly assigned to either aerobic endurance training using a bicycle ergometer or to flexibility, strengthening, and balance training. The endurance training starts with three 40-minute sessions per week for six weeks, then three 45-minute sessions per week for the next six weeks, conducted in small groups. The control group performs exercises focusing on stretching, strength, balance, and relaxation, with session durations increasing from 40 to 50 minutes over 13 weeks. During the 13-week study, participants undergo assessments of hippocampal volume, cognitive and executive functions, symptom severity, daily life functioning, and cardiovascular risk factors. The trial includes double-blind monitoring, and all participants receive individualized medication following standard treatment guidelines. The total study period allows researchers to observe brain structure and functional changes related to physical training in schizophrenia.

Researchers are investigating the brain and cognitive processes involved in how children, including those with mathematical learning disabilities (MLD), respond to interventions designed to improve their numerical skills. This study aims to understand the differences in learning and brain changes that support math skill development among children with various levels of math ability. The research uses a randomized controlled design to test an integrated symbolic and non-symbolic (iSNS) intervention. Children in the study will be randomly assigned to one of two groups for a 6-week period. One group receives the iSNS training, which focuses on improving the connection between symbolic numbers (like digits) and non-symbolic quantities to enhance number fluency. The other group participates in an active control intervention aimed at improving working memory skills related to visuospatial or verbal information. Participants complete training activities three days a week at home using a provided tablet and receive weekly one-on-one support from the research team. Participants will undergo assessments before and after the 6-week intervention, including MRI brain scans for those eligible, and behavioral tests measuring reaction time, accuracy, and brain activity related to number processing. Follow-up testing occurs six months later to evaluate long-term effects. The study measures changes in symbolic and non-symbolic number comparison tasks and brain activation to understand how these interventions impact learning and brain plasticity.

Researchers are investigating how different types of transcranial direct current stimulation (tDCS) applied to specific brain regions affect ankle tracking motor learning, motor adaptation, and brain connectivity. This study focuses on healthy middle-aged and older adults as well as patients with chronic subcortical stroke who experience difficulties with ankle control, balance, and movement. The goal is to better understand how stimulation of the primary motor cortex, posterior parietal cortex, and cerebellar cortex may influence these motor functions and brain connections. Participants are randomly assigned to one of four groups: stimulation of the primary motor cortex opposite the moving leg, stimulation of the posterior parietal cortex opposite the moving leg, stimulation of the cerebellar cortex on the same side as the moving leg, or a sham stimulation group. Each participant undergoes a 5-day skill acquisition phase where they complete daily 20-minute sessions of a sequential ankle tracking task using a custom-built system. Groups receiving active stimulation get 2 mA of anodal tDCS during this learning phase, while the sham group receives a brief ramp-up to 2 mA followed by no current during the session. During the study, researchers assess changes in ankle tracking performance and brain MRI data after one week. Additional measurements include fall history, attention, ankle muscle strength, mobility, walking ability, sensory and motor functions for stroke patients, and balance. Participants will be monitored closely to evaluate the effects of the stimulation and the learning task on motor functions and brain connectivity over the study period.

This research aims to evaluate the antidepressant effects of (2R,6R)-hydroxynorketamine (HNK) in adults aged 18 to 70 years with major depressive disorder (MDD) who have not responded well to previous treatments. The study compares the impact of HNK to a placebo on depressive symptoms, including mood, anxiety, and suicidal thoughts, using various rating scales and brain imaging techniques. It is a randomized, double-blind, placebo-controlled, crossover study conducted by the National Institute of Mental Health (NIMH). Participants will first taper off their current depression medications over 2 to 5 weeks and remain off these drugs for up to 2 weeks before starting study treatments. They will receive intravenous infusions of HNK or placebo four times over two weeks during each of two test sessions, with overnight stays at the clinical center after each infusion or for the study duration. The dose of HNK may be adjusted between 0.25 mg/kg and 2.0 mg/kg based on response and tolerability. After the first set of infusions and a drug-free period, participants will receive the alternate treatment for the second test session. Throughout the study, participants will undergo physical exams, blood tests, heart monitoring, mood and cognitive assessments, and symptom questionnaires. Optional brain imaging and activity scans may be performed. Researchers will track changes in depression severity using the Montgomery-Asberg Depression Rating Scale (MADRS) and other mood and anxiety measures. Safety and side effects will be carefully monitored through clinical evaluations, laboratory tests, and vital sign checks. The study is expected to continue until July 2027.

Researchers are studying people with mood disorders, including depression, bipolar disorder, and those at risk of suicide, to better understand how these conditions affect the body and how different treatments work. The study aims to identify predictors of response to antidepressant treatment and to find ways to predict which medications may help reduce thoughts of suicide. This observational study is conducted by the National Institute of Mental Health and involves participants who are already receiving clinical care for these conditions. Participants in this study are adults aged 18 years or older who have previously enrolled in a related protocol. They will undergo personalized treatments for their mood disorders and will be closely monitored through clinical ratings both in-person and remotely. The study includes three groups: individuals with bipolar disorder, individuals with major depressive disorder, and individuals at elevated suicide risk. The study typically lasts up to 12 weeks but may continue longer if treatment extends beyond this period. During the study, participants will have weekly interviews and complete questionnaires to assess their mood and suicidal thoughts. Optional tests such as psychological assessments, blood draws, sleep studies, and imaging scans are performed at the beginning and end of participation. The main outcomes measured are scores on the Montgomery Asberg Depression Rating Scale and the Scale for Suicidal Ideation, collected weekly. This helps researchers track treatment effects and understand the biological and clinical factors influencing response to therapy.

Researchers are evaluating the use of nebulized ketamine as a treatment for adults with moderate to severe depression in an inpatient psychiatric setting. This double-blind, randomized clinical trial compares nebulized ketamine with an active placebo, midazolam, to assess their effects on depressive symptoms. The study is designed to provide insights on whether inhaled ketamine can reduce depression when added to current medications and therapies. Participants will be randomly assigned to receive either nebulized ketamine at a dose calculated by body weight (1.5 mg/kg) or nebulized midazolam as an active comparator (0.03 mg/kg). The study involves 4 to 5 visits depending on the treatment group, with dosing days requiring in-person attendance and monitoring for at least two hours. All other visits can be conducted remotely. Vital signs will be regularly collected during the observation period following dosing. Adults aged 18 and older diagnosed with moderate to severe major depressive disorder will be screened and enrolled. Throughout the 8 to 10 day study period, researchers will measure changes in depression using the Montgomery-Åsberg Depression Rating Scale (MADRS) and other scales assessing suicide ideation, dissociative effects, sedation, and agitation. Safety monitoring includes vital signs and side effect assessments. The study aims to capture both immediate and short-term effects of the treatments on depressive symptoms.