17 Clinical Trials for Various Conditions
The purpose of this study is to determine the efficacy of Mindfulness Based Stress Reduction (MBSR) to alleviate stress, anxiety, and depressive symptoms, and improve attention among patients aged 60 or older who suffer from HIV-associated neurocognitive disorders (HAND) and have maximized treatment options.
This study will test the effect of liraglutide on cognitive function in HIV-infected overweight or obese subjects with type 2 diabetes.
1. To determine, in the Quillen College of Medicine HIV+ outpatient clinic, the prevalence of * NC (normal cognition ) * ANI (asymptomatic neurocognitive impairment ) * MCD (mild cognitive disorder ) * HAD (HIV-associated dementia ) 2. To determine whether the following variables affect the three categories of HAND * Time since first diagnosis of HIV infection * Anti-viral medications used * Age * Gender
It is estimated that over 1 million people in the United States have HIV infection. While HIV is treatable, there are still high rates of HIV-associated neurocognitive disorder (HAND). HAND is defined by low scores on memory testing. To meet the criteria for HAND, an HIV-infected individual has to have a low score on at least two different memory tests. It is estimated that 20-50% of people living with HIV have HAND. It is therefore still a common problem. While individuals with HAND typically improve on antiretroviral therapy for HIV, often this improvement is incomplete. Also, there are over 20 antiretroviral medications approved for HIV in the US. It is not clear if the specific choice of antiretroviral medication makes a difference in the improvement of HAND. The investigators have designed a small preliminary study in which subjects with and without HAND who have never been on treatment for HIV or have been off treatment for at least 6 months are followed for the first 12 months after starting antiretroviral therapy.The investigators will enroll a maximum of 46 subjects (23 subjects in each arm). Subjects will also be followed by their primary HIV medical provider. For the study, subjects will be followed for 48 weeks. There are three followup visits: 12 weeks, 24 weeks, and 48 weeks. Memory testing will be performed at baseline and each followup visit. Blood will also be taken at baseline and the three followup visits to measure changes in inflammation. A lumbar puncture will be performed at baseline and at 24 weeks to measure changes in inflammation and amount of HIV virus in the spinal fluid. There is also an optional lumbar puncture at the last study visit of 48 weeks
The purpose of this study is to describe the radiologic findings on brain MRI after ferumoxytol administration in HIV-infected patients with cognitive impairment.
The purpose of this study is to see if paroxetine and fluconazole are safe and effective as a treatment for problems with memory, concentration, thinking, and judgment in people who are infected with HIV. Paroxetine is an antidepressant approved by the FDA to treat major depression. Fluconazole is an antifungal medication approved by the FDA to treat fungal infections.
The purpose of this study is to longitudinally characterize and evaluate changes in synaptic density in the brain using novel positron-emission tomography (PET) scans; magnetic resonance imaging (MRI), and clinical laboratory markers associated with HIV-related injury in the central nervous system. This study will test hypotheses relating to the presence and mechanisms of aberrant brain structure at the synaptic level in living humans with virologically controlled HIV on antiretroviral therapy. To evaluate associations between PET imaging radiotracers \[11C\]UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein expressed in synapses, and PET \[11C\]PBR28 a measure of microglia function in the brain, the Yale PET center has developed an advanced approach of combining multiple distinct ligands in coordinated same-day PET imaging. Additionally, the study will evaluate the associations of this novel synaptic density marker with well-established clinical measures of neurocognitive performance and laboratory measures of blood and cerebrospinal fluid (CSF).
The general purpose of this observational study is to examine biomarkers associated with the pathology of neurodegenerative diseases to potentially develop novel therapeutic approaches.
In this study investigators will use a multi-modal imaging approach of MRS and fMRI to comprehensively assess the biological changes in the brain associated with EFV-based regimen (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local neurochemistry, and their correlation with neuropsychological function.
People with HIV (PWH) often suffer from cognitive impairments known as HIV-Associated Neurocognitive Disorder (HAND). Cognitive impairments in PWH are not fully captured by traditional neurocognitive assessment; thus, we must examine cognitive performance both within a task (inconsistency) and across cognitive domains (dispersion), called Intra-Individual Variability (IIV). IIV predicts cognitive impairment/decline, altered brain morphology, and neuropathology in many clinical populations. Conceptually, IIV results from "executive dyscontrol" or the efficiency (or inefficiency) with which executive control processes coordinate other cognitive processes/domains. Based on the Executive Dyscontrol Hypothesis and underlying calculations of IIV, one way to improve cognition in PWH is through interventions that target improvements in their most severely impaired cognitive domains. We hypothesize such improvements, in turn, should reduce the strain placed on executive functioning resources, freeing up resources needed to compensate for impairments in any domain and, in turn, reducing IIV. Computerized cognitive training, widely used in the study team's prior work, is ideally suited to target impairments in select cognitive domains using computerized cognitive training. In our systematic review of 13 cognitive training studies in PWH, we found cognitive training improved performance in the targeted domain. In this feasibility study, we will assess 150 PWH at baseline with the expectation to recruit 120 PWH with HAND. Then we will use a two-group pre-post experimental design of 120 adults with HAND including: 1) a Targeted Neurocognitive Training (TNT) group (n=60) to train each participant's two most impaired cognitive domains (e.g., attention \& memory) assessed from a neurocognitive battery at baseline, and 2) a no-contact control group (n=60). Aim 1 - Feasibility: To determine feasibility and acceptability of the intervention. Exploratory Aim 1 - Cognition: Compare adults who receive TNT to those who receive no training to determine whether they improve on the cognitive domains trained, show less cognitive IIV across domains and within a task, and demonstrate improved executive functioning. Exploratory Hypothesis 1: TNT will improve cognitive functioning in the targeted impaired cognitive domains. Exploratory Hypothesis 2: TNT will reduce cognitive IIV (both overall dispersion \& inconsistency). Exploratory Hypothesis 3: TNT will improve executive functioning. Exploratory Hypothesis 4: TNT will improve global cognition and reduce HAND severity. Innovation 1 - This is the first study to use IIV to guide cognitive training to target the most impaired cognitive domains to reduce cognitive IIV in HIV. Innovation 2 - This will be one of the first studies to prospectively include both types of cognitive IIV - dispersion and inconsistency - allowing us to examine the relationship between dispersion and inconsistency. Innovation 3 - The epicenter of HIV is in the Deep South where this study will occur.
Infection with HIV (the virus that causes AIDS) can lead to problems with brain function, such as memory, concentration, judgment, and the speed or control of hands and legs. Neurologists have called this condition HIV-associated neurocognitive disorder (HAND). This research is being done to see if insulin taken through the nose as a spray (intranasal insulin) can help people with HIV who are having problems with memory and brain function, or HAND. Participants will be given either insulin or placebo. A placebo is an inactive substance that looks like the study drug, but does not contain study drug. For this research study, the placebo will be a clear, saline-based liquid spray that looks like the insulin spray but has no insulin. Participants will not be told whether they receive insulin or placebo during the study. All participants will take the intranasal spray twice a day, about 30 minutes after a meal. Participants will use a specialized intranasal drug administration device. The total daily dose of insulin is 40 IU split between 20 IU in the morning and 20 IU in the evening. Participants will take the intranasal spray for 24 weeks. The researchers will record symptoms and side effects during the study. Procedures include neurocognitive testing of memory and brain function, two optional lumbar punctures ("spinal taps"), two MRI brain scans, monthly blood draws, and clinical assessments.
People infected with HIV often have cognitive dysfunction even if they are on antiretroviral therapy (ART) and have undetectable viral loads. The study evaluated if the addition of maraviroc (MVC) and dolutegravir (DTG) (which are two antiretroviral \[ARV\] medications) to participants' existing ART regimens improved participants' neurocognitive performance.
This study is being done to see if a drug called long acting methylphenidate (Concerta) is safe and effective as a treatment for problems with mental function in adults infected with HIV. A subset of patients with HIV-associated memory loss have a defect in the speed with which they learn and process information. Methylphenidate drugs, such as Ritalin or Concerta, have been shown on tests to improve the ability to rapidly absorb information; these tests are called "reaction time tests". These drugs are already FDA-approved to treat Attention Deficit Disorders: ADD or ADHD. At baseline, all subjects get tests of memory and brain function; then they are split into two groups. One group on this study will receive Concerta for 2 weeks, and a second group will receive a placebo x 2 weeks. After that period both groups will receive memory and other tests of brain function, and then the groups will switch. The first group will receive placebo and the second will receive Concerta x 2 weeks, followed by more memory and neurological tests. After that all subjects will have the option to receive Concerta for free for 8 more weeks. At the last visit all subjects get memory and brain tests again.
HIV associated neurological disorders (HAND), are a major problem even in ART treated people. HAND results from chronic inflammation which is largely attributed to expansion and activation of monocytes. These activated monocytes, some of which also carry virus to the brain, invade the CNS and release cytokines / chemokines resulting in further recruitment of monocytes, as well as release viral proteins which injure neurons and cause activation of other brain cells. Persistent monocyte/macrophage activation is thus a potential critical target for adjunctive therapy to treat or prevent HAND. The investigators therefore propose to study the effects of a statin drug (Atorvastatin), which has anti-inflammatory functions, on the monocyte activation status in ART treated HIV+ individuals. The investigators objectives are based on the hypothesis that Atorvastatin treatment will reduce the inflammatory and activated phenotype and function of monocytes which have been linked to HIV associated neuropathogenesis and occur in HIV infected subjects despite ART. In this study the investigators propose to 1) define the effect of Atorvastatin on monocyte activation in HIV infected / ART treated subjects in a double blind, placebo controlled crossover study
Background: - Human immunodeficiency virus (HIV) infection appears to cause problems with blood vessel function. These problems may add to some thinking and mood disorders found in people with HIV infection. Researchers want to evaluate HIV infected patients to see if blood vessel function contributes to thinking and mood disorders, such as early dementia and depression. To do so, they will compare study results between people with and people without HIV infection. Objectives: * To compare the thickness of blood vessel walls between people with and without HIV infection. * To study the relationship between blood vessel thickness and thinking and mood disorders. Eligibility: * Individuals between 25 and 55 years of age who have HIV infection. * Healthy individuals between 25 and 55 years of age. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Participants will have imaging studies of the brain and major blood vessels in the head and neck. * Participants will also have neuropsychological testing. These tests will look at memory, learning and thinking ability, attention, and mood. * Participants will have the option of coming back for repeat blood tests every six months and repeat imaging studies and neuropsychological tests every year, over 1- 4 years period.
Background: - Some people with human immunodeficiency virus (HIV) develop problems with thinking and concentration when the virus affects the brain. This is known as mild neurocognitive disorder (MND). Research has shown that some HIV medications do not get through the blood brain barrier very well. P-glycoprotein (P-gp) is a brain protein that is part of the blood brain barrier. Differences in the activity of P-gp may help explain why some people with HIV develop MND. It is also possible that MND is partly due to inflammation in the brain. Researchers want to study P-gp and its effect on MND and HIV infection. Objectives: - To study P-gp and brain inflammation related to HIV infection. Eligibility: * Individuals between 18 and 60 years of age who have HIV and either do or do not have MND. * Healthy volunteers between 18 and 60 years of age. Design: * Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected. * Participants will have one outpatient visit and one 3-day inpatient stay. * At the outpatient visit, participants will provide blood samples and have a lumbar puncture (spinal tap). The spinal tap will collect cerebrospinal fluid for study. * At the inpatient visit, participants will have two positron emission tomography (PET) scans of the brain. These scans will study brain activity and possible inflammation. One scan will involve a study drug called tariquidar, which blocks the activity of P-gp. A second lumbar puncture will be done before the first PET scan. Blood and urine samples will be collected daily.
In this study we will use a multi-modal imaging approach of MRS and fMRI to comprehensively assess the biological changes in the brain associated with EFV-based regimen (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local neurochemistry, and their correlation with neuropsychological function. In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, we propose to replace the EFV component with a new integrase inhibitor, elvitegravir (EVG) boosted with cobicistat (COBI), given as the EVG/COBI/FTC/TDF Single Tablet Regimen (STR) to evaluate the EFV-related neural alterations. This is a multidisciplinary study which involves a team of infectious disease experts in the field of HIV, neuroradiologists with expertise in fMRI and MRS techniques to study various central nervous system and psychiatric disorders and a psychiatrist with experience and expertise in research on abnormalities of affective and motivational processing in the context of neuropsychiatric disorders. We will utilize the established clinical research platform in the Infectious Disease outpatient clinical practice at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related studies and a large panel of HIV-infected patients motivated to be involved in clinically relevant research. We propose to use advanced neuroimaging to measure biologically changes in the brain associated with long-term EFV use with the following specific aims: 1. Determine changes in neurometabolites measured by MRS in the brain associated with long-term EFV use 2. Assess for alterations in neural activity correlated with affective symptoms associated with EFV vs STR use using fMRI, and their associations with changes in neurometabolites assessed by MRS, and with changes in cognition assessed by Trail Making and Digit Substitution Tests. 3. Determine changes in emotion, cognition and sleep quality after switching from EFV to STR, and how they correlate with subject treatment preference. This clinical study will extend our current understanding of EFV neurotoxicity by further defining the nature of these biological changes. Further elucidation of the neurobiological underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the quality of life and drug adherence of HIV-infected patients on ART, especially among older patients or those with baseline neuropsychiatric disorders, whom at baseline are more vulnerable to neurocognitive decline from long-term HIV infection.