Active clinical trials for "Fragile X Syndrome"

The purpose of this trial is to investigate the use of metformin in the treatment of Fragile X syndrome (FXS) patients. Metformin is an FDA approved compound with an established safety profile and minimal side effects that specifically targets and normalizes multiple aspects of the pathophysiology in FXS. This is a randomized double-blind placebo-controlled 2-arm parallel group design study of the drug metformin and placebo in FXS subjects with a primary outcome measure of safety/tolerability and secondary outcome measures on cognition, attention, anxiety, sleep, and physiologic and biochemical biomarkers.

Fragile X Syndrome (FXS) and Williams-Beuren Syndrome (WBS) are relatively rare disorders characterized by developmental delay associated to socio-communicative deficit and autistic-like behaviours. WBS has been considered for a long time as the "polar opposite" of ASD, given their hypersociable phenotype. Nonetheless, recent researches have emphasized similarities between ASD and WBS phenotypes. By following some authors "social abnormalities in ASD and WS can be characterized in terms of analogous difficulties in social cognition), and distinct patterns of social motivation which appears to be reduced in ASD and enhanced in WBS". More than opposite condition, these authors suggests that WBS and ASD could share the same difficult in comprehension of social relationship, with opposite pattern of social engagement (enhanced in WBS and weakened ASD). Given, these similarities authors suggest testing the feasibility and validity of therapy for ASD in children with WBS. Parent Mediated Therapy (PMT) is a group of "technique-focused interventions where the parent is the agent of change and the child is the direct beneficiary of treatment". PMT demonstrated evidence of effectiveness in socio-communicational improvement for children with ASD in a randomized controlled trial (RCT). Some recent researchers have extended the use of PMT to children with genetic disorders and autistic features, such as FXS. While showing encouraging results, the samples of research were limited. They main aim of this research is to to verify effectiveness of Cooperative PMT (CMPT) for socio-communicative deficit in children with FXS and WBS. Our hypothesis is that CPMT, in addition to conventional rehabilitation therapies (mainly speech therapy and occupational therapies), could contribute to the enhancement of socio-communicative skills and the reduction of behavioural problems. We also expected also an improvement in family quality of life and a reduction of parental stress.

The purpose of the study is to evaluate a 2-3 day treatment probe targeted to improving social gaze behavior in children with fragile X syndrome (FXS). The investigators will use the principles of Applied Behavior Analysis (ABA) to shape appropriate social skills. Importantly, the investigators propose to examine the effects of this treatment probe on brain and behavior.

Background: In human DNA, the Fragile X (FMR1) gene helps to regulate the nervous and reproductive systems. If the gene is abnormal, it can cause different kinds of problems, such as abnormal menstrual periods, decreased fertility, muscle tremors, and mental retardation. An abnormal FMR1 gene can also make a person more susceptible to other medical conditions, such as thyroid problems, high blood pressure, seizures, and depression. More research is needed on how abnormalities in the FMR1 gene can lead to these problems, and how often these problems appear in individuals with an abnormal FMR1 gene. Researchers are interested in developing a patient registry of women who have an abnormality in the FMR1 gene. This registry will allow researchers to follow participants over time and study possible effects of this abnormality on their general and reproductive health. Objectives: - To develop a patient registry of women with an abnormal FMR1 gene and monitor their general and reproductive health. Eligibility: - Women at least 18 years of age who have an abnormal FMR1 gene on the X chromosome. Design: The following groups of women will be eligible for screening for this study: Those who have a family member with Fragile X Syndrome or mental retardation Those who have (or have a family member who has) primary ovarian insufficiency, also known as premature menopause Those who have (or have a family member who has) certain neurological problems such as tremors or Parkinson's disease. Eligible participants will be scheduled for an initial study visit at the National Institutes of Health Clinical Center. Participants who have regular menstrual periods should schedule the visit between days 3 and 8 of the menstrual cycle; those who do not have regular periods may have the visit at any time of the month. In addition, all estrogen-based treatments (such as birth control pills) must be stopped for 2 weeks prior to the study visit. Participants will have a full physical examination, provide a medical history, and provide blood samples for immediate and future testing. Participants will return for yearly visits for the same tests for as long as the study continues. Participants who have or develop primary ovarian insufficiency related to the FMR1 gene will also have tests to measure bone thickness and will have a vaginal ultrasound to examine the ovaries. These tests will be scheduled for a separate visit, and will be repeated every 5 years for the duration of the study.

Glutamatergic transmission exploration using PET (Positron Emission Tomography) imaging in autism compared to Fragile-X Syndrome ( FXS) and Healthy Volunteers

Measurement of metabotropic glutamate receptor type 5 (mGluR5) binding capacity in the brain, may be a valuable tool in the early detection, understanding, or evaluation of Parkinson disease (PD), Huntington disease (HD), Fragile X syndrome (FXS), Autism Spectrum Disorder(ASD), Alzheimer's Disease(AD), and subjects with mild cognitive impairment (MCI). The goal of this study is to assess [18F]F-PEB positron emission tomography (PET) imaging as a tool to detect mGluR5 density in the brain of PD, HD, FXS ASD, AD, and MCI research participants and similarly aged healthy subjects.

The subjects that meet the inclusion and exclusion criteria and consent to participate in protocol 22003 will be offered participation in 22003A which will evaluate secreted protein before and after treatment with STX209 and placebo to determine if they correlate with effectiveness of treatment or susceptibility to treatment with STX209. These same subjects will also be asked to contribute a blood sample for DNA (deoxyribonucleic acid) collection. The investigators will study the DNA to determine if STX209 works better in people with specific gene variations, or to find new gene variations that predict how well STX209 works.

Biosynthesis of proteins is essential for growth and continued maintenance of the entire neuron including axons, dendrites, and synaptic terminals, and it is clearly one of the important biochemical processes underlying adaptive changes in the nervous system. Studies in experimental animals with the quantitative autoradiographic L [1 (14)C]leucine method have demonstrated a number of the physiological and pathological conditions in which changes in regional rates of cerebral protein synthesis (rCPS) occur. We have recently developed the first fully quantitative method for determining rCPS with positron emission tomography (PET). The PET method was adapted from the autoradiographic L [1 (14)C]leucine method; it uses L [1 (11)C]leucine as the PET tracer, dynamic scanning, and a kinetic modeling approach for quantification. This method was validated in nonhuman primates by comparison of PET measurements with those based on established biochemical and autoradiographic techniques. The objective of the present study is to examine the degree to which changes in rCPS in human subjects can be quantified with the L [1 (11)C]leucine PET method. We propose three studies to be carried out sequentially. In Part I we will establish the L-[1-(11)C]leucine PET method in human subjects. In Part II we will measure rCPS in normal control subjects in two states: awake and under deep sedation/general anesthesia with propofol. A difference in rCPS between these two states may indicate that we can detect activity-dependent protein synthesis with the PET method. In Part III we will study subjects with fragile X syndrome. This patient group was chosen since the affected gene in fragile X syndrome codes for a protein that is thought to be a negative regulator of message translation. Thus an effect on protein synthesis may be very close to the underlying genetic abnormality in fragile X syndrome. Regionally selective increases in rCPS have been found in studies in a mouse model of this disease. The present study will establish the sensitivity of the L [1 (11)C]leucine PET method to detect changes in rCPS in human subjects. A quantitative and sensitive method to measure rCPS with PET will augment the tools available for investigating the brain and its regional adaptive responses. Ultimately the method may have widespread applications, not only for the study of normal development and plasticity but also in clinical medicine, e.g., in the investigation of disorders of brain development, recovery from brain injury, and neurodegenerative diseases. SPECIFIC AIMS <TAB>Establish the L-[1-(11)C]leucine PET method for measurement of rCPS in human subjects. Evaluate the optimal scan time and the variability of the measurement in an individual. <TAB>Determine the effect of deep sedation with propofol on rCPS in normal human subjects. We will use the [1-(11)C]leucine PET method to evaluate lambda, i.e., the fraction of the precursor pool for protein synthesis that is derived from arterial plasma, and rCPS in the same subjects under awake and deep sedation conditions. I)<TAB>Hypothesis 1a. Deep sedation with propofol has effects on rCPS. II)<TAB>Hypothesis 1b. Deep sedation with propofol has effects on values of lambda. <TAB>Assess the sensitivity of the [1-(11)C]leucine PET method to detect differences in rCPS in subjects with fragile X syndrome. I)<TAB>Hypothesis 3a. There are regionally selective changes in rCPS in subjects with fragile X syndrome compared with age-matched healthy controls. Regions affected include hippocampus, thalamus, hypothalamus, amygdala, and frontal and parietal cortex. II)<TAB>Hypothesis 3b. In centrum semiovale, cerebellum, striatum and occipital and temporal cortex rCPS are unchanged in subjects with fragile X syndrome compared with age-matched healthy controls. III)<TAB>Hypothesis 3c. Values of lambda in the brain as a whole and in the regions examined are unchanged in subjects with fragile X syndrome compared with age-matched healthy controls. IV) Hypothesis 3d. The average rate of protein synthesis in the brain as a whole is unchanged in subjects with fragile X syndrome compared with age-matched healthy controls. ...

The aim of this study is to utilize neurophysiologic assessments, behavioral measures and clinical measures to assess how much deficits associated with Fragile X Syndrome from pre-dose to post-dose using pharmacology.

The subjects that meet the inclusion and exclusion criteria and consent to participate in protocol 22001 will be offered participation in 22001A which will evaluate secreted protein before and after treatment with STX209 and placebo to determine if they correlate with effectiveness of treatment or susceptibility to treatment with STX209. These same subjects will also be asked to contribute a blood sample for DNA (deoxyribonucleic acid) collection. The investigators will study the DNA to determine if STX209 works better in people with specific gene variations, or to find new gene variations that predict how well STX209 works.