Trials Today

This study will investigate whether transcranial direct current stimulation (tDCS) enhances the effects of cognitive training in older adults with depression.

Type: Interventional

Start Date: Feb 2023

open study

Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women. In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.

Type: Interventional

Start Date: Nov 2020

open study

The primary objectives are to investigate the safety and tolerability of BIIB091 monotherapy in participants with relapsing multiple sclerosis (RMS) (Part 1), and to evaluate the effects of BIIB091 combination therapy with Diroximel Fumarate (DRF) compared with the DRF monotherapy arm, on the key Magnetic Resonance Imaging (MRI) measure of active Central Nervous System (CNS) inflammation (Part 2). The secondary objectives are to evaluate the effects of BIIB091 monotherapy on the MRI measures of active CNS inflammation, to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on additional MRI measures of active CNS inflammation, to investigate the safety and tolerability of BIIB091 combination therapy with DRF in participants with RMS.

Type: Interventional

Start Date: Jul 2023

open study

The goal of this study is to learn about how children's sleep is related to their eating behaviors the next day, and to learn about factors that relate to eating behaviors and sleep health that are specific to preadolescent children living in rural communities.

Type: Observational

Start Date: Apr 2023

open study

Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare but potentially severe disease, in which patients develop pathogenic autoantibodies that specifically target the MuSK protein in the neuromuscular junction. This phase 1 study is being conducted to evaluate the safety of various dosing regimens of an investigational cell therapy, MuSK-CAART, that can be given to patients with anti-MuSK antibody positive Myasthenia Gravis (MuSK MG), who have active disease. Various dosing regimens of MuSK-CAART alone, in combination with cyclophosphamide (CY), and in combination with CY and fludarabine (FLU) will be evaluated. Treatment with MuSK-CAART may potentially lead to complete and durable remission of disease.

Type: Interventional

Start Date: Nov 2022

open study

A single subanesthetic dose infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder (TRD). A family history of an alcohol use disorder (Family History Positive, FHP) is one of the strongest identified predictors of an improved antidepressant response to ketamine. Like ketamine, alcohol is a functional NMDA receptor antagonist. FHP is associated with differential response to both alcohol, e.g. decreased body sway and plasma cortisol, and ketamine, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. cortical pyramidal cells. Preliminary clinical studies have demonstrated this acute glutamate "surge" in response to subanesthetic dose ketamine. Based on these findings, the investigators hypothesize that ketamine's enhanced antidepressant efficacy in FHP TRD subjects is, at least in part, attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder (Family History Negative, FHN). The investigators also hypothesize that alcohol similarly augments glutamate release in this bio- logically-enriched subgroup, which may be a more objective biomarker than family history status. To test these hypotheses, the investigators have designed a now two-site, open-label study of 21-65 year old medically and neurologically healthy, currently moderately-to-severely depressed TRD patients. In total, the investigators plan to recruit 25 FHP and 25 FHN TRD subjects. All subjects must not have a lifetime substance use disorder (except nicotine or caffeine), no lifetime history of an alcohol use disorder and socially drink. The experimental portion consists of two phases. The preliminary first phase is a medication taper (if needed) and psychotropic medication-free period. The experimental second phase comprises two pharmacokinetically-defined basal-bolus alcohol and one subanesthetic dose (0.5mg/kg x 40 minute) ketamine infusions. The first alcohol infusion will establish the pharmacokinetic profile for a subsequent alcohol infusion occurring during 7T-magnetic resonance imaging (MRI), both resting-state functional MRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) to detect glutamate in the ventromedial prefrontal cortex/ventral anterior cingulate cortex (vmPFC/vACC). The ketamine infusion will also occur during 7T-MRI. The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-ketamine infusion (baseline) to one week post-infusion, where the investigators observed ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine and alcohol challenge based on family history status. In summary, this study will provide key mechanistic information on ketamine's improved antidepressant efficacy in a biologically-enriched subgroup. This will contribute to the systematic development of more efficacious, personalized treatments for major depression in an effort to reduce its enormous public health burden.

Type: Interventional

Start Date: Apr 2014

open study

Huntington's Disease (HD) is an autosomal dominant disease manifested in a triad of cognitive, psychiatric, and motor signs and symptoms. HD is caused by a triplet repeat (CAG)expansion in the gene Huntingtin (HTT). This disease has classically been conceptualized as a neurodegenerative disease. However, recent evidence suggests that abnormal brain development may play an important role in the etiology of HD. Huntingtin (HTT)is expressed during development and through life. In animal studies, the HTT gene has been shown to be vital for brain development. This suggests that a mutant form of HTT (gene-expanded or CAG repeats of 40 and above) would affect normal brain development. In addition, studies in adults who are gene-expanded for HD, but have not yet manifested the illness, (pre-HD subjects) have significant changes in the structure of their brain, even up to 20 years before onset of clinical diagnosis. How far back these changes are evident is unknown. One possibility is that these brain changes are present throughout life, due to changes in brain development,though initially associated with only subtle functional abnormalities. In an effort to better understand the developmental aspects of this brain disease, the current study proposes to evaluate brain structure and function in children, adolescents, and young adults (ages 6-30) who are at risk for developing HD - those who have a parent or grandparent with HD. Brain structure will be evaluating using Magnetic Resonance Imaging (MRI) with quantitative measures of the entire brain, cerebral cortex, as well as white matter integrity via Diffusion Tensor Imaging. Brain function will be assessed by cognitive tests, behavioral assessment, and physical and neurologic evaluation. Subjects that are gene-expanded (GE) will be compared to subjects who are gene non-expanded (GNE). Changes in brain structure and/or function in the GE group compared to the GNE group would lend support to the notion that this disease has an important developmental component.

Type: Observational

Start Date: Jul 2005

open study

The purpose of this trial is to assess dose related safety, efficacy, and pharmacokinetics (PK) of INT-787 in participants with severe alcohol-associated hepatitis (sAH).

Type: Interventional

Start Date: Dec 2022

open study

Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) have unpredictable and varied speech outcomes after this treatment. Our research will prospectively document speech performance before, during and 6- and 12-months after STN-DBS in 80 surgically treated patients and compared with 40 non-surgical controls with Parkinson's disease. This study will provide unique insights into the role of STN in speech production, document speech outcome in a comprehensive fashion, identify factors that predict functional communication ability 12 months after STN-DBS, and test the feasibility of low frequency DBS in reversing DBS-induced speech declines in order to optimize treatment strategies for those living with Parkinson's disease.

Type: Observational

Start Date: Oct 2020

open study

In the current study, the investigators aim to understand the role of transcranial direct current stimulation (tDCS) in improving executive function across neuropsychiatric populations known to have deficits in this cognitive domain.

Type: Interventional

Start Date: Sep 2014

open study

The purpose of this multi-centered, NIH-sponsored study is to to develop an optimal protocol for using noninvasive 129Xe gas exchange MRI to detect changing disease activity in interstitial lung diseases (ILDs).

Type: Interventional

Start Date: Nov 2021

open study

Increasing evidence suggests that perceived social isolation and loneliness are major risk factors for physical and mental illness in later life. The prevalence of loneliness in US older adults warrants concern, with an estimated 30% of American adults aged 70 years and older reporting heightened loneliness. A wide variety of interventions have been developed to address social isolation and loneliness ranging from social facilitation to animal therapies. While many intervention studies have attempted to address loneliness, social isolation and related constructs in older adults, this literature is underdeveloped and there is not an established or widely accepted set of treatments. Moreover, existing treatments tend to be lengthy, burdensome, and result in high dropout rates. Brief, mechanism focused interventions are an alternative to more traditional forms of treatment. Because they are structured and brief, these treatments can be readily placed on the internet, making them extremely efficient, destigmatizing, and highly scalable. The investigators have developed and tested a web-based intervention called "Combating Social Isolation" (CSI) that the investigators believe offers an alternative to existing interventions for loneliness and social isolation in older adults. CSI evolved out of Interpersonal Theories of mood psychopathology (Joiner, 2005) and targets two risk factors central to social disconnection: perceived burdensomeness and thwarted belongingness (PB/TB). The investigators have one randomized clinical trial using CSI and are nearing completion of two other RCTs using this intervention. Evidence shows that CSI has very high levels of acceptability, and despite the brevity of the protocol (approximately 1 hour) can markedly impact loneliness. Moreover, reductions in these risk factors mediate later improvements in mental health outcomes and social disruption. The purpose of the current proposal is to adapt our existing protocol for older adults reporting loneliness and then obtain preliminary acceptability and efficacy data from a Phase II randomized clinical trial.

Type: Interventional

Start Date: Jul 2022

open study

The most pervasive sensory manifestation of TS is sensory over-responsivity (SOR). SOR is defined as excessive behavioral response to commonplace environmental stimuli. SOR is an integral but poorly understood facet of the TS phenotype, one intertwined with core elements of the disorder and worse QOL. This proposal seeks to clarify the mechanistic bases of SOR in TS. Adults with with TS will be recruited 1) to complete a standardized clinical symptom assessment battery and 2) to undergo electroencephalogram (EEG), autonomic, and audio-visual monitoring during tactile and auditory stimuli paradigms, as well as at rest.

Type: Observational

Start Date: Jul 2021

open study

The aims of this study are to 1) Conduct a randomized clinical trial of selective versus empiric diet plus pharmacologic therapy in high-risk stone formers and 2) Determine adverse effects from, and adherence to selective and empiric strategies.

Type: Interventional

Start Date: Aug 2022

open study

The purpose of this study is to investigate the safety and efficacy of the current hard gelatin capsule formulation of NRD135S.E1 80 mg once daily in the treatment of PDPN when administered for 13 weeks.

Type: Interventional

Start Date: Sep 2022

open study

This is a Platform Protocol to perform Phase II clinical trials in The Early Phase Pain Investigation Clinical Network (EPPIC-Net), under The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, related to the treatment of Painful Diabetic Peripheral Neuropathy (PDPN) in a platform setting to test multiple assets under a single protocol.

Type: Interventional

Start Date: Sep 2022

open study

This study will determine whether electrical stimulation of an area of the brain called the dorsolateral prefrontal cortex, which is important in determining the feeling of fullness after eating, affects how much food a person eats and weight loss over 4 weeks. It will also compare weight changes in people who attend weight loss counseling sessions and those who do not over this period of time. Obese, non-diabetic people between 18 and 60 years of age who are in good health and who live in the Phoenix, AZ, metropolitan area are eligible for this study. Candidates must have a body mass index of 35 kg/m(2) or more and weigh less than 350 pounds. Participants are admitted to the NIH inpatient unit in Phoenix for the first 9 days of the study for tests, which include meal tests to determine eating behaviors and caloric intake, blood and urine tests, glucose tolerance test, weight measurement, psychological assessments and DEXA scan to measure body fat. For 3 of the days, they will be asked to eat all of their food from automated vending machines. Some subjects receive transcranial direct current stimulation (TDCS). For this procedure, electrodes that conduct electricity are placed on the head and arm and the current is turned on for 40 minutes. Some tingling may be felt under the electrodes. Other subjects receive sham TDCS, with the current turned on only very briefly. After the evaluations, subjects are discharged home from the NIH unit and instructed to eat 25 percent fewer calories than they consumed while on a weight maintenance diet the first 3 days of their inpatient stay. They maintain the lower calorie diet at home for 4 weeks. During this period they come to the NIH unit 3 days a week to receive either real or sham TDCS. ...

Type: Interventional

Start Date: Jan 2009

open study

MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting metformin (reduced mass Glucophage XR) vs. matching placebo in 326 men and women with early and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55 years to 90 years. The RCT will last 18 months and have 4 visits: baseline, 6-months, 12-months, and 18-months. The RCT will be preceded by a screening phase followed by randomization and a titration period in which drug/placebo will be titrated from 500 mg a day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10 days. Participants will remain in the RCT on the tolerated dose, and included in analyses on an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and every 6 months. Brain MRI will be conducted in approximately half of the participants (186) twice, at baseline, and after the last study visit at month 18. We will also conduct brain amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using 18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical outcome of the study will be changes in the Free and Cued Selective Reminding Test. The secondary clinical outcome will be changes in the Alzheimer's Disease Cooperative Study Preclinical Alzheimer's Cognitive Composite. Secondary subclinical outcomes will be changes in cortical thickness AD signature areas, changes in white matter hyperintensity volume, changes in brain amyloid burden, changes in brain tau burden, and changes in plasma biomarkers of amyloid, tau, and neurodegeneration. The data coordinating center and Imaging Core is located at John Hopkins University. The PET coordinating center is located at UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will be located at Columbia. The Research pharmacy function will be shared by the University of Rochester, which will dispense randomization kits, and the University of Iowa, which will receive bulk metformin and identical matching placebo from EMD Serono.

Type: Interventional

Start Date: Mar 2021

open study

Emerging data suggest the gut microbiota regulates multiple mechanisms related to vascular aging, but no intervention targeting the gut microbiota has been tested in older adults without cardiovascular risk factors or cardiovascular disease. Early human data suggest an increase in potentially pathological gut metabolites such as trimethylamine-N-oxide (TMAO) are associated with older age, increased vascular stiffness, increased oxidative stress, and reduced nitric oxide (NO) bioavailability as evidenced by impaired endothelium-dependent vasodilation. Based on this data, the investigators hypothesize that supplementation with Lp299v will reverse human vascular aging in healthy older adults free of known traditional cardiovascular risk factors.

Type: Interventional

Start Date: Feb 2023

open study

Female suicide attempts occur more often in the weeks before and after menses onset, and have been linked to ovarian hormone withdrawal. The proposed project will use a two-week intervention to stabilize hormones in females with recent suicidal thoughts; this paradigm is a safe way to learn how cyclical changes in hormones and their metabolites influence short-term risk of suicide. The data acquired will contribute to our understanding of the biology of acute suicide risk and advance efforts to develop safe and effective treatments that eliminate predictable monthly worsening of suicide risk in reproductive-age females.

Type: Interventional

Start Date: Sep 2020

open study

Sleep disturbance is a common condition following traumatic brain injury (TBI) and impairs recovery and quality of life. While efficacious interventions exist many are not accessible to all patients due to a variety of factors (e.g., rurality, access to providers). Further, many of the available treatments have not been validated for individuals with moderate/severe TBI. The proposed study will evaluate a guided computerized version of cognitive behavioral therapy for insomnia (cCBT-I) against enhanced treatment as usual (ETU) in individuals with moderate/severe TBI.

Type: Interventional

Start Date: Jul 2022

open study

This is a single-center, parallel-arm, blind, sham-controlled, feasibility randomized controlled trial (RCT) to be conducted in healthy cesarean-born infants. Eligible infants will be randomized 1:1 to have their nose swabbed with either maternal vaginal secretions or a sterile swab (intervention vs. control group, respectively) following birth by cesarean section (C-section). The main hypothesis is that conducting an RCT assessing the utility of vaginal seeding in modifying the early-life upper respiratory tract (URT) microbiome of infants born by C-section is feasible and that the intervention is safe.

Type: Interventional

Start Date: Nov 2022

open study

This study examines a home-based computerized cognitive rehabilitation intervention in adults with multiple sclerosis compared to placebo (videogame). Patients are assessed through pre-and post neuropsychological testing.

Type: Interventional

Start Date: Apr 2021

open study

The PLANET Study aims to determine the impact of microplastics on intestinal inflammation and gut microbiome in order to understand the role of this pollutant on the risk of developing inflammatory bowel disease (IBD) as well as other diseases. With this information, the researchers hope to characterize better the role of environmental pollutants on IBD and develop novel strategies towards prevention.

Type: Observational

Start Date: Aug 2023

open study

Majority of breast cancer survivors are overweight or obese at time of diagnosis, putting them at increased risk for insulin resistance and Type 2 Diabetes Mellitus (T2DM). Women with insulin resistance at time of breast cancer diagnosis often have larger tumors, later stages of cancer and worse prognosis. Additionally, chemotherapy often leads to increases in insulin resistance and cognitive impairment. Many cancer survivors experience memory and brain function decline following chemotherapy that can last for years, and insulin resistance may contribute to worse cognitive outcomes in cancer survivors. Omega-3 polyunsaturated fatty acids (PUFAs) are anti-inflammatory nutrients that may help reduce insulin resistance and negative cognitive outcomes from cancer treatments. The purpose of this observational study with cross-sectional design is to investigate the relationship of omega-3 PUFAs with insulin resistance and cognitive function in obese breast cancer survivors. Due to the global pandemic caused by the coronavirus disease of 2019 (COVID-19), this study will be conducted entirely remotely using electronic data collection and remote finger-stick blood sample collection. The study will aim to enroll 80 racially and ethnically diverse female breast cancer survivors (age 45-75) who are postmenopausal, and 1 to 4 years post breast cancer diagnosis. Participants will complete study questionnaires online, and some cognitive tests will be completed through zoom sessions with trained study personnel. Participants will be mailed kits with thorough instructions to complete fingerstick blood sample collections and mail them back to the research lab. Upon receipt of blood samples and completion of all study questionnaires, participation will be complete.

Type: Observational

Start Date: Jan 2022

open study