22 Clinical Trials for Various Conditions
The purpose of this pilot study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a 1-site, randomized, within subjects, counterbalanced double-blind study of a single dose (200mg) of Mavoglurant and placebo.
Cognitive impairment occurs in as many as 80% of lupus patients and affective disorders, depression and anxiety, are also common. Both of these problems contribute significantly to disease burden and disability. Associations between serum anti-NMDAR Aab and cognitive and behavioral changes in human SLE have remained controversial, however, elevated titers of these Aabs in cerebrospinal fluid (CSF) correlate with severe central nervous system manifestations, such as coma and psychosis. The aim is to study the progression of disease (cognitive and behavioral impairment) over a 2 year period in SLE subjects with neuropsychologic and behavioral testing and correlates of disease progression using resting FDG-PET and serum Anti-NMDAR Aab. The correlations between hippocampal hypermetabolism, Anti-NMDAR Aab and memory impairment observed in the cross-sectional studies will be validated by baseline measurements in the proposed studies.
Objective: Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain. This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, \[18F\]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine. Study Population: The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-50 years old.; N=40/group). Design: Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use. Outcome measures: Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
The metabotropic glutamate subtype five (mGluR5) receptor is a protein found in the brain and is the target for the excitatory chemical messenger glutimate. The purpose of this protocol is to measure mGluR5 receptors in the brain using positron emission tomography (PET) and a research drug called \[18F\]SP203.
This is a double-blind, placebo-controlled, parallel group study to compare the effects of STP7 (mavoglurant) vs placebo control on i.v. cocaine's physiological and subjective effects in non-treatment seeking, cocaine-experienced males or females participants between 18 and 59 years of age. The primary objective of this study is to determine if there are clinically meaningful interactions between oral STP7 (mavoglurant) treatment concurrent with 20 and 40 mg i.v. cocaine infusions by measuring adverse events and cardiovascular responses including heart rate, blood pressure, and electrocardiogram (including corrected QT interval). The secondary objectives are: * To evaluate whether administration of STP7 (mavoglurant) alters the pharmacokinetics of cocaine and/or its major metabolite, benzoylecgonine. * To determine the pharmacokinetic of STP7 (mavoglurant) administered at a dose of 200 mg twice a day. * To evaluate whether STP7 (mavoglurant) treatment alters the subjective effects of cocaine measured by Visual Analog Scales (VAS) and Brief Substance Craving Scale (BSCS).
Objective: Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum, hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increased intracellular calcium levels. Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would impact clinical management of brain disorders characterized by disruptions in glutamatergic transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been hindered by the lack of high affinity and selective ligands for this receptor subtype. The present protocol will evaluate the ability of a new PET ligand, \[18F\]FIMX, to image and quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases: 1. Phase 0: screening whole-body scan; 2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent measurement of the parent radioligand in arterial plasma; 3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed doses of \[18F\]FIMX by performing whole body imaging; 4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma. Study Population: Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or whole-body imaging.. Design: This study will begin with a screening whole-body scan to confirm that the radioactivity has fairly broad distribution in several organs. For absolute quantification of mGluR1, 22 healthy controls will have brain PET imaging using \[18F\]FIMX and an arterial line. Up to 12 of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry, which does not require an arterial line. \<TAB\> Outcome Measures To assess absolute quantitation of mGluR1 with \[18F\]FIMX, we will primarily use two outcome measures: the identifiability and time stability of distribution volume calculated with compartmental modeling. In test-retest study, we will calculate the retest variability. To assess whole-body biodistribution and dosimetry of \[18F\]FIMX we will use the organ time-activity curves....
Objective Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the excitatory neurotransmission in the mammalian central nervous system (CNS). Based on pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent years it has become apparent that the receptors do not function alone, but in the company of auxiliary proteins that regulate their activity \[1\]. Some of these have been shown to modulate AMPA receptor trafficking, gating and pharmacology and are classified as transmembrane AMPA receptor regulatory proteins, or TARPs ( \>=-2, \>=-3, \>=-4, \>=-5, \>=-7, and \>=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy, neuropathic pain, and bipolar disorder \[1\]. In a preclinical collaboration with Eli Lilly, we developed a promising radioligand, 18F-TARP252 to image TARP \>=-8 using positron emission tomography (PET). This protocol covers three phases: * Phase 1: kinetic brain imaging to quantify TARP \>=-8 in brain relative to concurrent measurement of the parent radioligand in arterial plasma; * Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the radiation-absorbed doses by performing whole body imaging; * Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma. Study Population Healthy adult female and male volunteers (n=22, ages 18 - 55) will undergo brain imaging. An additional eight healthy volunteers will undergo whole body dosimetry analysis. Design For quantification of TARP \>=-8, 22 healthy controls will have brain PET imaging using 18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used. Outcome Measures To assess quantitation of TARP \>=-8 with 18F-TARP252, we will primarily use two outcome measures: the identifiability and time stability of distribution volume calculated with compartmental modeling. In test-retest study, we will calculate the retest variability. We will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to organs and effective dose to the body.
Background: - A small brain protein called the metabotropic glutamate receptor subtype 5 (mGluR5) may affect several brain diseases such as autism and depression. Researchers will use 2 radioactive chemicals (\[11C\]SP203 and \[11C\]FPEB) and a research drug (STX107) that can attach to the receptor, to figure out the best way to use positron emission tomography (PET) to see the mGluR5 receptor. They will use scans to monitor where the radioactivity goes. Objectives: - To find the best way to image the mGluR5 receptor in the brain. Eligibility: - Healthy volunteers ages 18 to 55. Design: * All participants will be screened with a medical exam at visit 1. In later visits, they may have a PET scan, when two small tubes are placed under the skin and they lie down in a scanner. They may have an MRI scan, when they lie down in a scanner. * Part 1 participants will have 2 more visits. They will have a PET brain scan using \[11C\]FPEB and will have blood drawn. Then they will have an MRI brain scan. * Part 2 participants will have 1 more visit, with a whole body PET scan using \[11C\]FPEB and blood drawn. * Part 3 participants will have 4 more visits, including 1 overnight stay at a hospital. Over all the visits, they will have 4 PET scans and 1 MRI brain scan. They will receive the research drug and injections of both chemicals. Blood will be drawn during the scans.
The purpose of this study is to assess the effect and safety of AZD6765 in patients with major depressive disorder who exhibit inadequate response to antidepressants. AZD6765 is a channel blocker of the N-methyl-D-aspartate (NMDA) class of glutamate receptors.
Background: - (11C)mGlu1 is a new drug that helps to show where a protein, mGluR1, is found in the brain. The drug contains a small amount of radioactivity that can be detected by imaging studies like positron emission tomography (PET) scans. By looking at the mGluR1 receptors, researchers hope to better understand how they are involved in general health, brain disorders, and addiction. Objectives: * To test how (11C)mGlu1 is distributed in the brain and body. * To measure how mGluR1 receptors display (11C)mGlu1 during imaging studies. Eligibility: - Healthy volunteers between 18 and 50 years of age. Design: * Participants will be screened with a medical history, physical exam, and blood and urine tests. This study requires four visits to the NIH Clinical Center. * Participants will have an initial evaluation, a magnetic resonance imaging (MRI) scan, a PET scan, and a final blood sample after the PET scan, all at different visits. * The MRI and PET scans will focus on the brain. Participants will receive (11C)mGlu1, and have scans to see how it shows up in the brain. * Some participants will have whole body imaging studies to see how (11C)mGlu1 shows up in the body.
In 2004, acamprosate was approved in the U.S. for abstinence maintenance, by decreasing craving, in alcoholic patients who have undergone detoxification. while a new anti-craving drug was encouraging, only 36.1% of the subjects treated with acamprosate remained abstinent for 6 months. Having the ability to identify treatment responsive individuals would have a major impact on the use of acamprosate.
Rett syndrome (RTT) is a disorder in which the nervous system does not develop properly. RTT generally affects girls, but there are some boys who have been diagnosed with RTT. Symptoms of RTT include small brain size, poor language skills, repetitive hand movements, and seizures. This study will evaluate the effectiveness of two drugs in treating the symptoms of RTT.
To evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of GATE-101 in normal human volunteers
The purpose of this study is to determine whether vilazodone is more effective than citalopram for the treatment of anxious depression. We will use neuroimaging to see whether there are changes in the brains of patients receiving the drug vilazodone that are different from those of citalopram. These changes may show that vilazodone affects the brain differently than most other kinds of standard antidepressant medications.
An open-label, long-term, safety study of AXS-05 in patients with major depressive disorder (MDD), including treatment resistant depression.
A Phase 3, randomized, double-blind, placebo-controlled, multicenter trial of AXS-05 in patients with major depressive disorder (MDD).
The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.
This a Phase 2a, multicenter, randomized, double-blind, placebo controlled 3 arm study to assess the safety and tolerability of multiple oral doses of REL-1017 25 mg and 50 mg as adjunctive therapy in the treatment of patients diagnosed with major depressive disorder (MDD). The patients will be adults with MDD who are diagnosed with a current MDE who have experienced an inadequate response to 1 to 3 courses of treatment with an antidepressant medication. This population will provide the opportunity to compare the safety and efficacy effects of treatment with an approved antidepressant in conjunction with REL-1017 versus the effects of an antidepressant alone. This study includes in-patient and out-patient periods.
There is an urgent need, therefore, to identify well-tolerated, orally available compounds that target the NMDA receptor as a novel treatment approach for TRD. The current project aims to test the safety, tolerability and efficacy of Nuedexta - containing the NMDA antagonist dextromethorphan.
The objective of the current study is to investigate the safety and efficacy of a single dose of intranasal (IN) ketamine in treatment-resistant depression (TRD).
NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is based on the observation that PCP, which blocks the NMDA receptor, produces symptoms and cognitive impairments similar to schizophrenia. Efforts to enhance the function of the NMDA receptor with glycine and D-cycloserine have met with limited success. An alternative approach would be to use the drug acamprosate. Acamprosate, FDA-approved for maintenance of sobriety after detoxification from alcohol, seems to act through modulation of the NMDA receptor. In the lab, acamprosate has been noted to act as an antagonist when the NMDA receptors are maximally stimulated but as an agonist when NMDA receptor stimulation is minimal. This "smart drug" action makes acamprosate appealing for use in schizophrenia. If acamprosate works as a smart drug in patients, then we would predict that it would enhance the function of NMDA receptors in schizophrenia and improve cognition and the symptoms of the illness. Additionally, acamprosate seems to modulate the NMDA receptor in novel ways distinct from glycine and D-cycloserine. We will also see if the response to acamprosate differs based on whether participants do or do not have a past history of alcohol use disorders.
This study will evaluate the effectiveness of the experimental drug, Org 24448, for short-term treatment of depression. It will examine the effects of the drug on symptoms, such as low mood and persistent sadness, poor sleep and appetite, poor motivation and lack of enjoyment of things people normally enjoy, negative thinking, and feeling slowed down or having trouble concentrating. It will also assess whether the drug improves cognitive function, especially memory. Patient with major depression who do not have a serious, unstable medical illness and who are 21 to 55 years of age may be eligible for this study. Candidates are screened with a psychiatric and medical history, diagnostic interview, physical examination, electrocardiogram, blood tests and, for women, a pregnancy test. Participants are tapered off anti-depression drugs (and any other medications not allowed on the study) over a 3-week period and then begin a 2-week drug-free period. During these 2 weeks they have an electroencephalogram (EEG) with light stimulation, and those whose EEG indicates a seizure disorder are excluded from the study. Also at the beginning of the drug-free period they begin taking a placebo ("sugar pill") twice a day. After 2 weeks on placebo, some patients begin treatment with Org 24448, while others remain on placebo. They continue the medication for 8 weeks, during which time they have a weekly check of vital signs, blood and urine tests, and rating scales for depression and anxiety. Level of functioning is evaluated twice during the study. After 8 weeks of treatment, patients have a physical exam, electrocardiogram (ECG), EEG, blood tests, and begin to come off the study drug, tapering the medication over a week. In addition to the above procedures, some patients undergo the following tests during the 2-week drug-free period and again toward the end of the 8-week medication phase: * Neuropsychological testing, including measurements of cognitive abilities such as memory, attention, problem-solving, and language skills. * Positron emission tomography (PET): This nuclear medicine test provides information about different brain regions. The patient lies on a table in the PET scanner (similar to a computed tomography (CT) scanner), with a mask placed over his or her face that helps keep the head still. A sugar fluid with a radioactive material attached to it is injected into a catheter (plastic tube) that has been inserted into a vein in the patient's arm. The scanner detects ...