Depression

Researchers are evaluating the safety, tolerability, and effectiveness of CYB003, a deuterated psilocin analog, compared to a matching placebo as an additional treatment for people with Major Depressive Disorder (MDD). The study focuses on adults aged 18 to 85 who have moderate to severe depression and have not responded adequately to a stable antidepressant medication. This phase III trial aims to add knowledge about treating MDD by assessing CYB003 alongside current antidepressants and psychological support. Participants are randomly assigned to one of two groups. One group receives 16 mg of CYB003 in two dosing sessions spaced about three weeks apart, while the other group receives a placebo on the same schedule. All participants continue their current antidepressant treatments and receive manualized psychological support throughout the study. Those who do not respond to placebo may join a later extension trial to receive CYB003. Throughout the trial, participants undergo several assessments, including the Montgomery-Åsberg Depression Rating Scale (MADRS) at multiple time points from screening to 42 days after treatment begins. Other evaluations include the Beck Depression Inventory, Clinical Global Impression Scale, Generalized Anxiety Disorder scale, and Quality of Life questionnaire. Participants are monitored for safety, treatment response, and tolerability, with the total study period lasting around six weeks after dosing begins.

Researchers are investigating the relationship between functional measures of balance and gait and objective kinetic and kinematic parameters in people with Multiple Sclerosis (MS). This cross-sectional observational study aims to understand how biomechanical gait and balance data collected through the Vicon motion analysis system relate to clinical assessments of balance, gait, and physical performance. The study seeks to identify which biomechanical factors are most closely linked to functional abilities and mobility challenges in MS. Participants will attend a single laboratory session where they will undergo biomechanical analysis of balance and gait using the Vicon motion capture system. They will also complete standardized functional tests including the Mini Balance Evaluation Systems Test, Functional Gait Assessment, Short Physical Performance Battery, and a 2-Minute Walk Test. Additionally, they will fill out questionnaires assessing fear of falling and fatigue and have their lower-limb spasticity evaluated with the modified Ashworth Scale. During the session, which takes about 40 minutes for the primary kinetic and kinematic analysis and additional time for functional assessments, researchers will collect detailed movement data alongside clinical measures. This data will be analyzed to explore correlations between biomechanical parameters and functional outcomes. The study includes assessments of postural control, gait performance, physical endurance, fatigue, and spasticity. The findings aim to improve understanding of movement impairments in MS and support better clinical assessments and rehabilitation approaches.

Young adults aged 18 to 25 who experience frequent thoughts about killing themselves are the focus of this study, which evaluates the (cost-)effectiveness of Attachment Based Family Therapy (ABFT) compared to Treatment As Usual (TAU). Suicide is a leading cause of death among young adults, and current treatments have limited success. This trial aims to determine if involving family through ABFT can better reduce suicidality and improve outcomes, informing clinical guidelines and care practices in Belgium and the Netherlands. Participants are randomly assigned to one of two groups: the experimental group receives ABFT as an add-on to TAU, which includes treatments like antidepressants, CBT, or DBT, with weekly ABFT sessions lasting about 16 weeks. The control group receives TAU alone, allowing up to four sessions of systemic family therapy. ABFT focuses on strengthening parent-child attachment bonds to provide a supportive base for young adults, involving parents or caregivers actively in therapy. Throughout the study, suicidality is measured at baseline, immediately after intervention, and at follow-ups 3, 6, and 12 months post-intervention using tools like the Suicidal Ideation Questionnaire Junior. Researchers also assess depressive symptoms, family functioning, attachment, quality of life, and healthcare costs. The trial includes 138 participants across multiple sites, with double-blind randomized allocation. Safety, adherence, and cost-effectiveness are closely monitored during and after the treatment period.

Researchers are investigating the antidepressant effects of 40 Hz light stimulation in adults with Major Depressive Disorder (MDD). This study builds on findings from Alzheimer's disease research, where 40 Hz flickering light therapy showed promise in halting disease progression and improving cognition. The trial aims to explore whether this non-invasive neurostimulation can similarly benefit patients with depression by inducing neuroplasticity and reducing neuroinflammation. Participants will use a Neurostimulation System (NSS) device at home for one hour daily over six weeks. The device delivers either a 40 Hz invisible spectral flicker (active setting) or continuous non-flickering white light (sham setting) in a double-blinded, randomized placebo-controlled design. After the six-week treatment period, there is a two-week follow-up to monitor ongoing effects. During the study, participants will undergo assessments at multiple timepoints including baseline, weeks 1, 3, 6, and 8. These evaluations include depression severity rating using the Hamilton Depression Rating sub-scale (HAM-D6), cognitive tests such as facial expression recognition and memory assessments, sleep quality monitoring, and quality of life questionnaires. Researchers will also analyze EEG data to explore brain activity changes related to treatment. Medication and psychotherapy regimens should remain stable throughout the study period.

This research aims to evaluate the effects of 5-hydroxytryptophan (5-HTP) and creatine monohydrate as augmenting agents for the treatment of major depressive disorder (MDD) that is resistant to standard antidepressants. The study focuses on addressing the potential impact of relative hypoxia on depression through alterations in brain bioenergetics and serotonin synthesis, investigating biological markers linked to depression and antidepressant response. This phase 2 trial involves participants diagnosed with MDD who have not fully responded to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Participants will be randomly assigned to one of three groups for 8 weeks: a low dose group receiving 5-HTP 100 mg twice daily plus creatine 5 g daily, a high dose group receiving 5-HTP 200 mg twice daily plus creatine 10 g daily, or a placebo group receiving matched placebos for both agents. The study will assess the biological and clinical effects of these treatments by measuring brain phosphorus magnetic resonance spectroscopy (31P-MRS), resting state functional connectivity imaging (fcMRI), and plasma serotonin levels, aiming to replicate and extend findings from an earlier phase. During the study, participants will undergo clinical assessments including the 17-item Hamilton Depression Rating Scale to monitor changes in depression severity, as well as secondary measures like the Montgomery-Asberg Depression Rating Scale. Brain imaging and blood tests will be conducted to evaluate changes in brain energy metabolism and serotonin. Safety monitoring includes screening for medical conditions and pregnancy, with study visits scheduled over the 8-week treatment period. The total duration of participation aligns with the treatment timeline, and the study uses quadruple masking to ensure unbiased results.

Researchers are investigating how the antidepressant citalopram affects the brain's response to emotional information, focusing on the amygdala, a key brain area involved in depression. This study explores how different parts of the amygdala react to positive and negative emotional stimuli, using advanced brain scanning technology to understand the underlying brain mechanisms. Participants will receive a single oral dose of either 20 mg citalopram or a placebo in a randomized, double-blind design. After dosing, participants will undergo high-strength 7T fMRI brain scans while viewing emotional faces. This precise imaging allows researchers to observe how citalopram influences specific subfields of the amygdala during emotional processing. Participants will be screened for medical and psychiatric health before joining. During the study, brain activity and behavioral responses such as accuracy and reaction time during a gender discrimination task will be measured about three hours after dosing. The study includes safety monitoring and lasts for a few hours on the study day, focusing on neural and behavioral outcomes related to emotional processing.

Researchers are studying major depressive disorder (MDD), a mental health condition marked by episodes of depression called major depressive episodes (MDEs). The study aims to find out if levels of an enzyme called PDE4B are lower in the brains of people experiencing an MDE. It also seeks to determine the best scanning time using a radioactive tracer called [18F]PF-06445974, how reliable the scans are, and whether PDE4B levels relate to clinical symptoms. The study also tests if PDE4B binding in the brain can be blocked by the drug apremilast. Participants will undergo up to five clinic visits including screening, physical exams, blood tests, heart function tests, psychiatric assessments, and brain imaging. Brain imaging includes MRI scans and PET scans where the tracer [18F]PF-06445974 is injected intravenously. The PET scan lasts up to four hours with a break. Some participants may have a second PET scan, a lung scan, or receive oral apremilast. Monitoring of heart rate, blood pressure, breathing, and blood sampling during scans is included. During the study, participants answer questions about their mental state and undergo clinical rating scales. Researchers measure PDE4B levels in the brain and assess how these relate to symptoms. Safety monitoring includes checking medical history, ECG, labs, and ability to tolerate scans. The main outcome is measuring PDE4B distribution volume over 36 months. Participants’ usual care continues throughout, and healthy volunteers are also included for comparison.

Researchers are evaluating a community health worker-delivered mental health counseling intervention delivered remotely via a mobile health app to reduce anxiety and depression among people living with HIV in Florida. This pilot randomized controlled trial aims to assess the preliminary effectiveness of this adapted positive affect counseling approach compared to the standard version of the app and usual mental health care. The study is sponsored by the University of Florida and focuses on improving mental health outcomes in this population. Participants will be randomly assigned to one of two groups. The intervention group will receive approximately five weekly 60-minute individual counseling sessions via secure video calls through a modified PositiveLinks app that includes enhanced mental health resources. If symptoms do not improve, participants may be referred to a licensed mental health professional. The control group will use the standard PositiveLinks app, which provides feedback on anxiety and depression symptoms and a list of local mental health resources without counseling. During the study, data will be collected from participants' electronic medical records and the app for about six months after enrollment. Researchers will measure changes in anxiety and depression levels at three months as primary outcomes. Participants will provide informed consent before joining, and there is no masking or blinding in the trial. The study will monitor mental health symptoms and the use of counseling through app data and medical records to evaluate the intervention's preliminary effectiveness.

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this period.

Researchers are evaluating whether adding ketamine tablets to standard antidepressant therapy can reduce depressive symptoms in adults with Major Depressive Disorder (MDD). This pilot Phase II trial focuses on whether ketamine, given alongside a new antidepressant, decreases depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) after one week of treatment. The study includes adults aged 18 to 75 years with moderate to severe single or recurrent MDD episodes. Participants will receive four doses of Ketamine Hydrochloride Prolonged-Release Tablets (240 mg) over eight days at the clinic while starting a new standard antidepressant chosen by their physician. The ketamine treatment ends after one week, but the antidepressant therapy continues. This trial includes only one treatment group with all enrolled patients receiving ketamine alongside antidepressants. During the study, participants complete various questionnaires and rating scales at screening, treatment, and follow-up visits. Blood samples are collected at five visits to monitor side effects and explore biomarkers. Follow-up continues for three weeks after ketamine treatment ends, with assessments of depression severity, anxiety, suicide risk, physical activity, sleep patterns, and inflammatory biomarkers. The total participation lasts about four weeks.