Clinical Research Directory

Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients

This is a multicenter, randomized, double-blind, placebo-controlled study in pediatric patients who are experiencing major depressive episodes (MDEs) associated with a primary diagnosis of bipolar I or bipolar II disorder as confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5).

Brexpiprazole Treatment for Bipolar I Depression

Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I and type II depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.

Ketogenic Intervention for Bipolar Depression

The purpose of this study is to assess the clinical correlates of therapeutic precision ketosis in bipolar depression and to evaluate the cardiometabolic correlates associated with therapeutic precision ketosis in bipolar depression.

A Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression

The purpose of this study is to o evaluate the antidepressant efficacy of the PEA in Bipolar Depression and the association between antidepressant response with endogenous cannabinoids and cytokine levels

Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression

This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory, monitoring, and integration psychotherapy sessions (psilocybin-assisted psychotherapy, or PAP). Using fMRI (functional magnetic resonance imaging), the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD. The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose (25 mg) of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder, with 2 or more failed treatment trials (i.e., treatment resistant bipolar depression \[TRBD\]). Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task (determined by fMRI one day after the psilocybin dose) and antidepressant effects (determined by changes in the Montgomery-Åsberg Depression Rating Scale \[MADRS\] scores over time, during the one-week period post-psilocybin dose). This is a single-arm, open-label clinical trial wherein all participants will receive the same study intervention. Hypothesis: Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD.

EEG Microstate and Neuroinflammatory Biomarkers in Older Age Patients With Major Depressive Disorder Receiving ECT

This study aims to investigate the neurophysiological and inflammatory changes associated with electroconvulsive therapy (ECT) in older age patients diagnosed with Major Depressive Episode, Major Depression, and Bipolar Disorder, using microstate analysis derived from resting-state electroencephalography (EEG) recordings. Within this scope, EEG recordings obtained before and after ECT will be compared to determine the relationships between changes in microstate parameters and inflammatory marker levels, clinical variables, and psychometric scale scores reflecting clinical improvement. Peripheral blood samples collected from the same patient group will be analyzed for complete blood count parameters as well as levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), soluble glycoprotein 130 (sgp-130), soluble interleukin-6 receptor (sIL-6R), interferon gamma-induced protein 10 kDa (IP-10), and C-reactive protein (CRP). In addition, inflammatory indices, including the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR), will be calculated. The association between baseline levels of these biomarkers and treatment response will be evaluated. Moreover, changes in biomarker levels following ECT will be statistically examined in relation to clinical scale scores and EEG microstate parameters. Although microstate analysis and inflammatory biomarkers have each been extensively investigated in psychiatric disorders, studies evaluating these two biomarkers together, particularly with the inclusion of healthy control participants, in the older age population remain limited. In this regard, the present study aims to evaluate the effects of ECT on older age patients using objective neurophysiological indicators, contribute to the understanding of the pathophysiology of depression at the level of brain networks, and provide a scientific basis for the development of personalised treatment approaches in the future.

Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder

Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.

Ketamine Associated ACC GABA and Glutamate Change and Depression Remission:

This is a feasibility study and the goal of this project is to evaluate whether peak ACC GABA and glutamate, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission, Montgomery Asberg Depression Rating Scale (MADRS) total score of \<10, to the anti-glutamatergic antidepressant ketamine. As MRS is expensive, we also aim to study a correlation between change in peripheral metabolites (GABA and glutamate) and central GABA and glutamate levels.

Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.

RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)

The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.

A Randomized Study of Azetukalner Versus Placebo in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression)

X-CEED is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of azetukalner in adult participants diagnosed with bipolar I or II disorder who are currently in a depressive episode (bipolar depression).

An Open-label Study of Azetukalner in Bipolar I or II Depression (X-CEED-OLE)

X-CEED-OLE is a Phase 3, multicenter, open-label study to evaluate the long-term safety, tolerability, and efficacy of azetukalner in adult participants who successfully completed an antecendent Phase 3 azetukalner bipolar depression study.

Efficacy and Safety Assessment of Temporal Interference Stimulation to Improve Bipolar Depression

The aim of this study was to explore the efficacy and safety of temporal interference stimulation to improve bipolar depression, as well as to explore the corresponding neuroimaging mechanisms using magnetic resonance and electroencephalogram to provide novel intervention protocols and objective indicators of efficacy prediction for depressive episodes in bipolar disorder.

Task-State-Based Temporal Interference Stimulation (TI) to Improve Depression in Patients With Bipolar Disorder

The purpose of this study is to investigate the efficacy and safety of temporal interference stimulation (TI) in improving depressive episodes of bipolar disorder, to analyze the therapeutic principle of TI in bipolar disorder depressive episodes based on task state MRI scanning, and to explore the abnormal regulation mechanism of anhedonia neural circuit.

SYNCED - SYNChronized Eating in Bipolar Depression Study

Bipolar disorders (BD) are a group of complex disorders that impact mood, behaviour and cognition and are known to cause significant suffering and impairment. Circadian rhythm (your internal day/night "clock") disruption, which can involve changes in sleep-wake cycles, frequently occurs in BD. Both depression and mania are accompanied by circadian disruption. These disruptions are hypothesized to lead to mood worsening, metabolic dysfunction and inflammation. If circadian dysfunction plays a significant role in the symptoms and trajectory of BD, then treatment approaches that target these functions may lead to better outcomes. One such approach is dietary interventions. Time restricted eating (TRE) is a dietary tool that restricts the eating to an 8-12 hour window, without changing diet quality or caloric intake. Studies involving time restricted eating have been done in other conditions with promising results. There have been no studies done for mood disorders in general or bipolar disorder specifically. In this proposal, the investigators will assess two dietary interventions (TRE and nutritional counselling) to examine how TRE may represent a safe and viable adjunct to traditional treatments. The investigators aim to compare TRE with nutritional counselling, while all participants continue to receive usual care. Participants will receive support from a registered dietician and will be instructed on dietary habits. Half of participants will receive nutritional counselling and half will be asked to do TRE. Those in the TRE group will be asked to select a 10-hour window to consume all food and non-water beverages for the 8-week period. Participants will be asked to complete a screening visit to determine eligibility, and then will complete questionnaires at baseline, week 4 and week 8 examining symptoms of their illness and cognition. Participants will also provide a blood sample at baseline and week 8 for standard biochemistry tests, pregnancy testing (if applicable), and to examine inflammatory markers. Participants will also wear an actigraphy watch which provides wireless continuous monitoring of movements and ambient light. The primary outcome is feasibility and acceptability (do people agree to participate, complete the study, and follow the intervention; what do they think of the intervention). Secondary outcomes include changes in depression, anxiety, sleep, and cognition. Exploratory outcomes include inflammatory markers and circadian disruption.

Focused Ultrasound Amygdala Neuromodulation

The purpose of the study is to examine the feasibility and potential efficacy of low-intensity focused ultrasound as a method of modulating amygdala function to promote improvements in symptoms of an affective disorder. Ultrasound is frequently and safely utilized for diagnostic purposes. In this study, the investigators will utilize magnetic resonance imaging (MRI) and neuronavigation to target the left amygdala and apply ultrasound. This will be conducted once a day, 5 days a week, for 3 weeks. This will be an open-label, single-arm trial.

Dopamine D3 Receptor Occupancy in Bipolar Depression

Bipolar disorder is a common condition that can cause significant disability and risk for suicide. Second generation antipsychotic medications can be used to treat depression in bipolar disorder, yet we do not know how they work. Here, we will use a recently approved medication, cariprazine (Vraylar), to treat participants with bipolar depression. They will have brain imaging with PET scans before and during treatment to understand how the medication may be working. Particularly, we will look at the role of the D3 dopamine receptor.

Probiotics to Prevent Relapse After Hospitalization for Bipolar Depression

The purpose of this study is to determine if taking a probiotic supplement versus a placebo will reduce relapse and improve the clinical course among participants who have been hospitalized for bipolar depression.

Low Field Magnetic Stimulation: Imaging Biomarkers in Geriatric Bipolar Depression

The protocol involves functional Magnetic Resonance Imaging acquisitions immediately before and after Low Field Magnetic Stimulation treatment on two separate days in a sham controlled, randomized trial, in order to assess the physiologic effects of Low Field Magnetic Stimulation on brain function in a geriatric population with bipolar depression.

Theta-Burst Stimulation for Bipolar Depression

The purpose of this trial is to determine if intermittent theta-burst stimulation (iTBS) can reduce the symptoms of depression in treatment-resistant bipolar disorder. To do this, some of the participants in this study will receive treatment with active iTBS stimulation, while others will receive sham iTBS stimulation. Participants will come for 30 days of either active iTBS or sham iTBS, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.

Empagliflozin Adjunctive Therapy in Bipolar Depression

Bipolar disorder is a long-term mental health condition that causes mood changes, with depressive episodes being the most frequent and disabling. Many people do not fully recover with current treatments, showing the need for new therapeutic options. Recent research shows that insulin resistance (IR), a condition in which the body does not respond well to insulin, is common in people with bipolar disorder. It is linked to more severe mood symptoms, poorer treatment response, and higher risk of heart disease. IR may raise inflammation and affect how the brain uses energy, which can influence mood regulation. Empagliflozin is a medicine approved for type 2 diabetes. In addition to its metabolic and heart benefits, studies suggest that it may also protect the brain and reduce inflammation, possibly helping to improve mood. This open-label, proof-of-concept clinical trial will test how well empagliflozin works and how safe it is as an add-on treatment for people with bipolar depression and insulin resistance. A total of 20 adults with bipolar disorder type I or II, currently in a depressive episode, will take part in the study over a 12-week period. The main goal is to see whether empagliflozin can lower depressive symptoms, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Other measures include changes in insulin resistance and incidence of adverse events. The study aims to explore whether improving insulin resistance can help both mood and metabolic health in people with bipolar disorder, guiding future clinical research.

Adjunctive Bright Light Therapy in Patients With Bipolar Depression and Eveningness

This is a randomized placebo-controlled trial to examine the efficacy of six-week bright light therapy as adjunctive treatment for patient with bipolar depression and eveningness.

University of Iowa Interventional Psychiatry Service Patient Registry

The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient ("personalized medicine").

PROgram To Enhance Cardiovascular Risk Trough an Intervention of Nutrition in Bipolar Disorder

Individuals with Bipolar Disorder (BD) have twice the risk of being affected by metabolic comorbidities and a 1.8-fold increased risk of mortality from cardiovascular diseases when compared to the general population. These factors are fundamental in the 14-year reduction in the life expectancy of people with TB reported in recent meta-analyses. This occurs mainly due to the increased inflammation associated with the disease, the adverse effects of pharmacological treatments and unhealthy lifestyle habits that are more common in people diagnosed with BD. Nutrition has been studied as an adjunctive treatment in other psychiatric disorders, but there is a lack of studies about the role of nutrition in TB. Considering that diet can impact metabolic health, this randomized controlled study aims to evaluate the effect of a nutritional intervention on cardiovascular risk in patients with TB. The intervention is based on the dietary pattern recommended in the Dietary Guidelines for the Brazilian Population and will be applied by a registered dietitian. According to the literature, the sample size will be 72 individuals with TB (36 in the control group with usual treatment + 36 in the intervention group added to the usual treatment). The intervention will be carried out in 7 individual sessions and 8 group sessions with specific themes. The primary aim of this protocol will be an intervention to contribute to cardiovascular health - verified by serum markers, anthropometric measurements and the Framingham Cardiovascular Risk Score (algorithm used to estimate an individual's 10-year cardiovascular risk). The secondary stages will be the adherence of the intervention and the impact on the quality of life of the participants. The possible positive results of this nutritional intervention can open new clinical perspectives. Meaning that might show that better food choices can protect the cardiovascular health of individuals with TB, leading to a reduction in morbidity and mortality associated with the disease.