Clinical Research Directory

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.

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.

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).

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.

Efficacy, Tolerability, and Cognitive Effects of Deep Transcranial Magnetic Stimulation for Bipolar Depression

The aim of this study is to evaluate the feasibility and efficacy of deep transcranial magnetic stimulation (dTMS) as an add-on treatment for bipolar depression. Meanwhile, we aim to evaluate the effect of dTMS on cognitive function of bipolar depressive patients. We hypothesize dTMS would improve depressive symptoms and cognitive function in bipolar disorder.

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.

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.

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.

Deep Brain Stimulation of Treatment-Resistant Bipolar Depression

This study is only enrolling at Baylor College of Medicine. The other research locations listed serve to support data analysis only. This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression (TRBD) symptoms in patients with severe cases. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment. Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms. There may be no directly benefit from taking part in this study. This study is expected to last 20 months and involves 3 main steps. 1. Medical, psychiatric, and cognitive evaluations. 2. Implantation of a brain stimulation system. 3. Follow up after implantation of device, including programming, recording, and psychiatric testing. There are risks and benefits to this study which need to be considered when deciding to participate or not. Some of the risks are from surgery, the DBS device and programming, the tests involved, and potential loss of confidentiality, as well as other unknown risks. Some of the more serious risks involved in this study and the percentage that they occur: 1. Bleeding inside the Brain (1 to 2 percent). 2. Infection from the procedures (3 percent) 3. Seizure caused from the procedures (1.2 percent) However, the benefit of this study is that it may help relieve or decrease TRBD symptoms. This form of treatment has shown to reduce symptom severity in other cases. This could potentially improve quality of life and activities in daily routines. There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms, as well as enhanced Deep Brain Stimulation techniques. Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits. These visits also include 8 separate, 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit (NBU). These 24-hour sessions will occur at multiple points throughout the study (1 week prior to surgery, the week preceding device activation, the week following activation, then after 2 weeks, 4 weeks, 6 months, 9 months, and 12 months). Participants will need to stay locally for the week of the NBU stay (typically Monday through Friday). Study visits will include clinician administered assessments and questionnaires, subject reported assessments, neuropsychological testing, and mobile behavioral assessments which will occur around 23 visits over the course of 20 months.

Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure

Schizophrenia, bipolar and major depressive disorders collectively affect over 10 million people across the EU and are associated with annual healthcare and societal costs in excess of 100 billion Euros. When diagnosed with one of these disorders, patients are prescribed psychotropic medication such as antidepressants, mood stabilisers or antipsychotics. It is unknown whether this first-line treatment will be successful. After this first-line treatment fails, usually a second-line treatment is initiated, and when this is not successful either a third-line treatment is initiated. Third-line treatments are quite successful, especially when compared to second-line treatments. The research question is whether the third-line treatments (early-intensified treatments) when used earlier in the disease course for schizophrenia, bipolar and major depressive disorders. If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments and adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs.

HD-tDCS for Adolescent Bipolar Depression Targeting S1

This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex in adolescents with bipolar depression. Participants will be randomly assigned to receive either active HD-tDCS or sham stimulation, in addition to routine clinical care. Biological data, including neuroimaging, blood biomarkers, voice and facial features, Photoplethysmography (PPG), Electroencephalography (EEG), and behavioral data, will be collected to explore potential predictors of treatment response.

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.

The Effect of a Six Week Intensified Pharmacological Treatment for Bipolar Depression Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.

Bipolar disorders affect approximately 4.5 million people across the European Union (EU) and are associated with high annual healthcare and societal costs. Bipolar disorder I and II represent disorders that cause extreme fluctuation in a person's mood, energy, and ability to function, in which symptoms of (hypo)mania and depression alternate. The depressive episodes of bipolar disorders are often referred to as bipolar depression (BD). In other words: it is a phase/state of the disorder. For many patients with BD, the depressive polarity is often more pervasive and more debilitating than manic states, with estimates that depressed mood accounts for up to two-thirds of the time spent unwell, even with treatment. The burden of not received an effective treatment for BD is high: more severe psychopathology, higher rates of unemployment, more hospitalisations, lower quality of life, lower cognitive functioning, risk of suicide, comorbidities and poorer social and occupational functioning and thus more carer burden. For BD, the treatment guidelines are very heterogeneous, amongst other reasons because the disease is heterogeneous and treatments should be tailored to the patients. There is no clear treatment algorithm and it cannot yet be predicted which treatment will be effective. Especially the place of adjunctive antidepressants is under debate. Usually, for psychiatric disorders (including bipolar disorder), a patient is considered to be treatment-resistant is two medicinal treatments have been tried (in sufficient duration and dosage) without sufficient success. For BD, there is no consensus on when to consider a patient as treatment-resistant, but the most common definition is after one prior treatment failure. This raises the research question whether adjunctive antidepressants to treat BD should be introduced earlier in the treatment. Additionally, The INTENSIFY trial is part of the larger Horizon 2021 project, with the central goal of paving the way for a shift towards a treatment decision-making process tailored for the individual at risk for treatment resistance. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for treatment resistance across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression.

Magnetic Resonance-Guided Focused Ultrasound Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression

The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD).

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).

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.

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.

Effects of Acute Exercise and Ibuprofen on Symptoms, Immunity, and Neural Circuits in Bipolar Depression

This is a 2x2, within-subjects, cross-over trial to test the anti-depressant effects of acute exercise in 20 participants with bipolar depression. Participants will complete four experimental sessions, two with an exercise challenge and two with a resting control condition in a counterbalanced order. Participants will receive either 800mg of ibuprofen or placebo before exercise or rest in order to test whether blocking the inflammatory response to exercise interferes with the neural and psychological effects of exercise.

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.