Clinical trials

The investigators will conduct the formative work that is necessary to develop a novel, multi-level intervention (inclusive of patient- and provider-level components), which will increase awareness of and modify the complex, intersecting factors that contribute to cervical cancer development among cisgender women with HIV (WWH). In Aim 1a, the investigators will explore the multi-level barriers and facilitators to follow-up appointment attendance among WWH who have had a recent high-risk abnormal Pap smear in the past six months, via qualitative interviews with WWH who have either attended at least one follow-up visit (n\<10) or have not yet attended a follow-up visit (n\<10). In Aim 1b, the investigators will explore provider awareness of the HIV-cervical cancer relationship and perspectives on barriers to retention in care via qualitative interviews (n\<8). For Aim 2, The study team will leverage the Aim 1 data, develop a patient-level intervention (1-2 sessions) and a provider toolkit, with the goal of increasing retention in care among WWH who are at heightened risk for cervical cancer. The study team will seek feedback on the manual and the toolkit from providers and from a community advisory board. In Aim 3a, the investigators will test the feasibility and acceptability of the intervention in a pilot randomized control trial (RCT) (n\<60). The study team will also assess (1) changes in self-efficacy to attend cervical cancer-related healthcare appointments pre-post intervention, (2) the proportion of women who attend a follow-up appointment, and, of those participants, (3) the proportion of women who complete the next phase of treatment. In Aim 3b, the investigators will explore the feasibility of intervention implementation in the clinic and acceptability of the provider-level intervention components in qualitative interviews with providers, clinic staff, the interventionalists, and other key stakeholders (n\<10).

Alzheimer's Disease (AD) is associated with impairments in both gait and cognition, significantly increasing fall risk. Falls are a leading cause of injury-related disability in older adults, and individuals with AD experience a nearly threefold higher rate of falls compared to neurotypical older adults. There is an urgent need for fall prevention interventions tailored to the unique deficits of individuals with AD. Converging evidence suggests that interventions aiming to reduce fall risk in AD should target both gait and cognition. Rhythmic music interventions, such as Rhythmic Auditory Stimulation (RAS) can harness global brain activation and auditory-motor entrainment to facilitate high-intensity exercise to alleviate AD-related neurocognitive and gait dysfunction. This study aims to assess the neural correlates of gait dysfunction in people with AD, evaluate if baseline neurocognitive impairment is predictive of the effects of RAS, and evaluate RAS benefits for individuals with AD.

Pregnant women in South Africa (SA) are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) use during pregnancy is both safe and effective in preventing HIV. However, posttraumatic stress (associated with intimate partner violence and/or other traumas) and depression negatively impact PrEP adherence among women in SA. Addressing posttraumatic stress and depression will likely improve PrEP adherence and persistence (i.e., sustained PrEP adherence over time) during pregnancy and breastfeeding, which are periods of dramatically increased HIV risk. The overarching goal of this proposal is to develop and test the feasibility and acceptability of a cognitive behavioral intervention that targets common underlying factors of posttraumatic stress and depression to improve PrEP adherence and persistence during pregnancy and the postpartum transition. The specific aims of the project are to (1) explore the mechanisms by which posttraumatic stress and depression impact PrEP adherence and persistence during pregnancy via qualitative interviews; (2) develop a brief PrEP adherence and persistence intervention (\~4 sessions) that reduces the negative impact of psychological mechanisms common to posttraumatic stress and depression on PrEP use, and builds behavioral skills to improve self-care; and (3) evaluate the feasibility, acceptability, and signals of preliminary efficacy of the intervention, which will be integrated into antenatal care, in a pilot randomized controlled trial. All data will be collected in the Midwife Obstetrics Unit (MOU) in Gugulethu, a peri-urban settlement and former township community outside of Cape Town, SA.

This research study aims to adapt and evaluate the acceptability and effectiveness of Project EMPOWER-OCD for socioeconomically diverse caregivers of patients with OCD. Designed to reduce obstacles (e.g. months long time commitment, high cost, transportation) to treatment that caregivers may be particularly prone to, project EMPOWER-OCD will provide targeted intervention of accommodation - a well-established, potentially modifiable risk factor for child anxiety, OCD, and its related disorders - in a single, self-guided session via an online format.

The current study tests the feasibility and effectiveness of a youth intervention designed to provide meaningful leadership opportunities through the acquisition of leadership skills as well as mindfulness practice, LEAP: Leadership, Engagement, and youth Action Program with Mindfulness. The goal of this project is to determine whether the Leadership, Engagement, and youth Action Program with Mindfulness (LEAP) curriculum, which was developed with youth, is a feasible and effective intervention for fostering leadership and well-being. The investigators seek to understand whether LEAP can support wellbeing for youth as a strategy to increase youth mental, emotional, and behavioral (MEB) health.

The goal of this clinical trial is to understand how different types of word categories, along with the language children hear from their parents, support bilingual toddlers' word learning. This study will address two main questions: (1) How are the words toddlers know related to the words their parents use? and (2) How does what toddlers already know help them learn new words in two languages? The investigators will compare bilingual toddlers with typical development to those with language delay to determine whether they learn new words in similar ways. Children's vocabulary knowledge will be assessed using standardized parent-report checklists. To examine how different types of categories support learning, the study will focus on two early-acquired categories: animals and clothing. The investigators will compare what parents report about their children's vocabulary with how children learn new words within each category. To understand the role of parent input, children and their parents will engage in shared book reading and play activities using materials from one of the target categories. Parent-child interactions will be video recorded. Children will also complete an eye-tracking task in which they learn new words in two languages within the same category.

The purpose of this clinical trial is to answer the question: can the investigators predict which adults with social anxiety disorder (SAD) will successfully respond to treatment? To answer this question, the investigators plan to recruit 190 adult participants who experience extreme forms of social anxiety to undergo brain imaging before and after 12 weeks of group cognitive behavioral therapy (CBT). Adults in the SAD group who do not respond enough to group CBT may be offered the opportunity to complete an additional 12 weeks of individual CBT while receiving SSRI medication (sertraline, see below) for SAD. Data collected from participants who experience anxiety will be compared to a group of 50 participants with little or no social anxiety, who will serve as a comparison group.

The goal of this randomized controlled trial (RCT) is to test the feasibility of an 10-week telehealth mindful exercise intervention compared to a telehealth exercise only intervention for people with knee osteoarthritis (OA). This RCT will be fully digital with all recruitment, assessments, and intervention being conducted remotely.

Persistent developmental stuttering affects more than three million people in the United States, and it can have profound adverse effects on quality of life. Despite its prevalence and negative impact, stuttering has resisted explanation and effective treatment, due in large part to a poor understanding of the neural processing impairments underlying the disorder. The overall goal of this study is to improve understanding of the brain mechanisms involved in speech motor planning and how these are disrupted in neurogenic speech disorders, like stuttering. The investigators will do this through an integrated combination of experiments that involve speech production, functional MRI, and non-invasive brain stimulation. The study is designed to test hypotheses regarding the brain processes involved in learning and initiating new speech sound sequences and how those processes compare in persons with persistent developmental stuttering and those with typical speech development. These processes will be studied in both adults and children. Additionally, these processes will be investigated in patients with neurodegenerative speech disorders (primary progressive aphasia) to further inform the investigators understanding of the neural mechanisms that support speech motor sequence learning. Together these experiments will result in an improved account of the brain mechanisms underlying speech production in fluent speakers and individuals who stutter, thereby paving the way for the development of new therapies and technologies for addressing this disorder.

The purpose of this research study is to compare muscle activation, changes in pain sensitivity, and brain function, between different walking conditions, including walking to music, walking to metronome, and walking without music or metronome.

This project optimizes high-resolution tACS to improve memory in healthy older adults, advancing drug-free approaches for ADRD. We test stimulation schedules and develop an adaptive, brain-guided tACS system to strengthen memory-supporting networks.

This study aims to understand how people use different types of feedback to control their speech. When an individual speaks, the brain relies on several systems at the same time, such as sensory systems that monitor an individuals own voice and the movements of their speech muscles, and a motor system that builds and reads out learned motor patterns. The investigators are studying how these systems work together and how they differ across individuals. Investigators will test 90 adults between 18 and 50 years old, including people who stutter, people with dyslexia, and people with typical speech and reading development. Participants will complete several short speech tasks in which the sounds they hear or the movements of their jaw or larynx are briefly changed. These responses will be used to measure each person's speech motor skills and to estimate the settings of a computer model called "SimpleDIVA," which simulates how the brain controls speech. Participants will also complete an MRI scan so investigators can measure the structure and connectivity of different brain regions. These measures will help investigators understand how individual differences in the brain relate to the speech motor control skills we observe. Participants will also complete sessions with noninvasive brain stimulation (transcranial current stimulation, or tCS) to examine how stimulation of specific areas of the brain affects responses during the speech tasks. The knowledge gained from this study will help researchers understand why speech motor skills vary across people and how differences in neural function may contribute to conditions such as stuttering and dyslexia.

This study will examine how two important brain circuits - one involving the subthalamic nucleus (STN) and one involving the ventral intermediate nucleus of the thalamus (VIM) - contribute to learning and producing speech sequences. Participants will include two groups: 1. individuals with Parkinson's disease who have deep brain stimulation (DBS) devices targeting the STN and 2. individuals with essential tremor who have DBS devices targeting the VIM. Participants will complete speech tasks involving the learning and repetition of novel sound sequences. During some parts of the study, DBS stimulation will be temporarily turned on or off in a controlled research setting. This will allow researchers to examine how stimulation affects both the learning of new speech sequences and the production of previously learned sequences. All STN participants and most VIM participants will also be equipped with a cutting-edge DBS system, the Percept PC, which will enable the recording of deep brain activity during the tasks. The results of this study will improve our understanding of how different brain circuits support speech learning and production. In particular, this study will help to differentiate the roles of the STN and VIM in learning the ordering of speech sounds within a syllable from learning of speech sequences containing multiple syllables. This knowledge may help guide future approaches to optimizing DBS settings to improve both movement and speech outcomes in individuals with neurological disorders, as well as provide greater general insight into how these brain structures contribute to speech production and learning.

Tests whether age-related visual deficits arise from disrupted alpha-gamma coupling in visual cortex (V1) and MT. Uses fMRI, source-resolved HD-EEG, and personalized complex-waveform HD-tACS to (1) quantify aging effects on phase-amplitude coupling, (2) drive PAC into a preferred "gamma-at-alpha-troughs" state, and (3) bidirectionally change perception by aligning gamma to alpha troughs vs peaks. Two five-day, double-blind, sham-controlled studies (n=120 each) target contrast sensitivity (V1) and 3D shape-from-motion (MT), aiming for mechanistic insight and remediation in older adults with implications for ADRD.

The purpose of this study is to investigate several approaches for improving spatial perception and speech intelligibility in multitalker listening situations for hearing-aid users. The hypotheses are that spatial perception and speech intelligibility will be improved by (1) increased high-frequency audibility, (2) speech envelope enhancement, and/or (3) appropriate sound image externalization.

The investigators will evaluate the theory that Alzheimer's disease-related memory impairment derives from the inefficient orchestration of rhythmic activity at the level of large-scale cortical networks. The results as expected to elucidate AD-related pathophysiology and set groundwork for the development of drug-free interventions for improving memory in AD and related dementias.

Although multiple treatments for OCD exist, slow symptom decrease, high remission, and significant side effects for some OCD patients limit their efficacy. More research into the precise neural mechanisms and linked cognitive functions in OCD is also necessary. To address both concerns, this study by Dr. Reinhart and his team will test a new, non-invasive, and well-tolerated neuromodulation method for reducing OCD symptoms, based on reward-related rhythms of the orbitofrontal cortex (OFC; a brain region responsible for reward, decision making and other crucial functions that is affected by OCD). This proposal is based on highly encouraging preliminary data in both subsyndromal and treatment-resistant populations that shows rapid reductions in OCD behaviors that last at least 1-3 months. Using high-definition transcranial alternating current stimulation (HD-tACS) guided by EEG brain wave recordings, the study will test whether repetitive modulation of relevant rhythm activity in the OFC can lead to rapid (within five days) and sustainable (up to three months) OCD symptom reduction. This research aims to increase knowledge of OCD and development of effective treatment with minimal side effects.

This cluster-randomized crossover trial evaluates the impact of two different packaging formats for small-quantity lipid-based nutrient supplements (SQ-LNS) on adherence and acceptability among caregivers of young children in Northern Ghana. SQ-LNS are a proven intervention for reducing child malnutrition, but optimizing packaging formats may improve adherence and scalability. Eight health facilities participating in growth monitoring services will each receive both formats: a 1-day sachet (20g daily) and a 7-day bulk container (140g weekly), with the order of delivery randomized. Each packaging format will be distributed for one month before cross-over. The primary outcomes are adherence (measured through caregiver self-report and sachet counts) and acceptability (assessed via caregiver interviews). Secondary outcomes include caregiver preference, ease of use, and qualitative insights into feeding practices, beliefs, and packaging usability. This implementation research study uses a convergent mixed-methods design, integrating quantitative adherence and acceptability data with in-depth interviews and structured observations to inform real-world program implementation. Findings will guide policy and program decisions for integrating SQ-LNS into child health platforms in Ghana and other low-resource settings.

The aim of this research study is to test the feasibility of a physical and mental health intervention (Positive Minds, Strong Joints or PMSJ) for Black adults with knee osteoarthritis (OA).

The emergence of crawling and walking is significantly delayed in infants with Down syndrome (DS), but the development of independent mobility provides infants with new opportunities for exploring the environment and interacting with objects and people that are important foundations for early learning. Increasing infant mobility early in development with body weight supported harness systems may support infant exploration, communication, and social interaction. This project will set the stage for the first clinical trial of a mobility-related intervention specifically tailored for infants with DS by testing the feasibility of harness systems with infants and families and identifying measures that will serve as primary outcome variables. Upon completion of this pilot project, necessary preliminary data and experience required for an in-home, high-impact clinical trial for infants with DS will have been obtained.

The goal of this clinical trial is to learn if a novel psychosocial intervention is effective in helping adults over 50 with serious mental illness (SMI) increase their social connections and participate in more healthy lifestyle activities. The Hopeful and Healthy Living (HHL) intervention combines social skills training and training in cognitive self-management strategies in order to help older adults build healthy lifestyle and social routines. We predict that: * Individuals who participate in the HHL intervention will improve more in perceived social support (i.e., what people get from relationships such as reliance, reassurance of worth, attachment) and loneliness at the 4-, 8-, and 12-month follow-up assessments than those who receive treatment as usual (TAU). * Individuals who participate in the HHL intervention will improve more in overall psychosocial functioning at the 4-, 8-, and 12-month follow-up assessments than those who receive TAU. * Individuals who participate in the HHL intervention will improve more in cognitive functioning at the 4-, 8-, and 12-month follow-up assessments than those who receive TAU. * Individuals who participate in the HHL intervention will improve more in healthy behaviors (sleep, activity, diet) at the 4-, 8-, and 12-month follow-up assessments than those who receive TAU. In this trial, participants will be either receive the HHL intervention or participate in their regular treatment activities (treatment as usual). HHL vs. TAU will be compared to see if there are any differences in social support, cognition, loneliness, psychosocial functioning, or healthy lifestyle activities including physical activity, sleep, and diet. Participants will be asked to complete an interview-based assessment at baseline, 4-months, 8-months, and 12-months. After completing the baseline assessment, those who are in the experimental group will participate in the 16-week long HHL group intervention.

The treatment of generalized anxiety disorder (GAD) in an accessible manner represents an unmet need for those with cardiovascular disease (CVD), given that patients with CVD experience numerous barriers for in-person treatment engagement. The research plan for the proposed pilot project will entail: (1) open study of the acceptability of the digital intervention (N=5), followed by (2) recruitment and randomization of 90 individuals with a history of acute CVD events and clinical levels of GAD symptoms to dCBT or a waitlist (Control) condition, using a 1.5:1 allocation (dCBT:Control).

Spatial navigation is a fundamental human behavior, and deficits in navigational functions are among the hallmark symptoms of severe neurological disorders such as Alzheimer's disease. Understanding how the human brain processes and encodes spatial information is thus of critical importance for the development of therapies for affected patients. Previous studies have shown that the brain forms neural representations of spatial information, via spatially-tuned activity of single neurons (e.g., place cells, grid cells, or head direction cells), and by the coordinated oscillatory activity of cell populations. The vast majority of these studies have focused on the encoding of self-related spatial information, such as one's own location, orientation, and movements. However, everyday tasks in social settings require the encoding of spatial information not only for oneself, but also for other people in the environment. At present, it is largely unknown how the human brain accomplishes this important function, and how aspects of human cognition may affect these spatial encoding mechanisms. This project therefore aims to elucidate the neural mechanisms that underlie the encoding of spatial information and awareness of others. Specifically, the proposed research plan will determine how human deep brain oscillations and single-neuron activity allow us to keep track of other individuals as they move through our environment. Next, the project will determine whether these spatial encoding mechanisms are specific to the encoding of another person, or whether they can be used more flexibly to support the encoding of moving inanimate objects and even more abstract cognitive functions such as imagined navigation. Finally, the project will determine how spatial information is encoded in more complex real-world scenarios, when multiple information sources (e.g., multiple people) are present. To address these questions, intracranial medial temporal lobe activity will be recorded from two rare participant groups: (1) Participants with permanently implanted depth electrodes for the treatment of focal epilepsy through responsive neurostimulation (RNS), who provide a unique opportunity to record deep brain oscillations during free movement and naturalistic behavior; and (2) hospitalized epilepsy patients with temporarily implanted intracranial electrodes in the epilepsy monitoring unit (EMU), from whom joint oscillatory and single-neuron activity can be recorded.

HIV transmission remains a significant public health concern, especially among men who have sex with men (MSM). Condomless anal intercourse (CAI) continues to be the major route of transmission for MSM. Thus, to reduce the incidence of HIV, it is critical to identify how contextual risk factors influence CAI and develop behavioral strategies that modify risk factors directly or reduce their influence on behavior. This study will examine the mechanisms through which one of the central contextual risk factors, heavy drinking, influences sexual decision processes in the natural environment and test the benefit of a brief intervention designed to reduce sexual risk behavior among those who engage in heavy drinking.

The goal of this clinical trial is to learn if non-invasive brain stimulation (called transcranial stimulation) can enhance the benefits from auditory training in people who struggle to understand one talker when many people are talking at the same time. The main questions it aims to answer are: * Does transcranial stimulation improve speech-on-speech understanding in people who struggle with this task? * Does transcranial stimulation enhance the benefits of a commercially available auditory training program? Researchers will compare transcranial stimulation to sham stimulation (no stimulation is applied during the listening task). Participants will: * Receive login information to an online auditory training program to complete at home over 2 weeks * Visit the laboratory 4 times to receive transcranial stimulation while listening to speech-on-speech: once before at-home training, two times during the at-home training period, and once after at-home training has ended