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| Sponsored by: |
National Institute of Mental Health (NIMH) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00362843 |
Purpose
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 diso...
| Condition |
|---|
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Fragile X Syndrome |
| Study Type: | Observational |
| Official Title: | PET Measurement of Regional Rates of Cerebral Protein Synthesis in Subjects With Fragile X Syndrome |
| Estimated Enrollment: | 98 |
| Study Start Date: | August 2006 |
| Estimated Primary Completion Date: | July 2008 (Final data collection date for primary outcome measure) |
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 24 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
Fragile X subjects:
Male subjects, 18-24 years of age, with diagnosis of fragile X syndrome will be considered. Diagnosis will be confirmed by molecular genetic testing. Subjects with CGG repeat sequences greater than 200 and methylation of FMR1 will be included.
Control:
Male subjects, 18-24 years of age will be considered.
EXCLUSION CRITERIA:
Fragile X subjects:
Fragile X subjects with either repeat size or methylation mosaicism will be excluded. Fragile X subjects on psychotropic medications will be excluded from the study. Fragile X subjects who have received radiation doses for research purposes exceeding 4 rem (whole body effective dose) in the previous 12 months will be excluded.
Fragile X subjects in whom MRI is contraindicated will be excluded. Subjects in whom propofol is contraindicated will be excluded. Fragile X subjects on medications that interfere with blood coagulation will be excluded. In addition, fragile X subjects with respiratory illnesses or cardiovascular diseases will be excluded as there might be increased risk of complications with sedation/anesthesia. Subjects positive for HIV will be excluded from the study.
Control:
Subjects with premutation alleles, i.e., repeat length between 55 and 200 will be excluded. Subjects with IQ less than 90 or subnormal language skills will be excluded. Subjects on psychotropic medication will be excluded from the study. Subjects who have received radiation doses for research purposes exceeding 3.5 rem (whole body effective dose) in the previous 12 months and subjects for whom MRI is contraindicated will be excluded. Subjects in whom propofol is contraindicated will be excluded from Part II. Subjects on medications that interfere with blood coagulation will be excluded. Subjects with any previous history of psychiatric or neurological disease, as assessed by the Structured Clinical Interview for DSM-IV (SCID), will be excluded. In addition, subjects with respiratory illnesses or cardiovascular diseases will be excluded from Part II as there might be increased risk of complications with sedation/anesthesia. Subjects positive for HIV will be excluded from the study.
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Study ID Numbers: | 060214, 06-M-0214 |
| Study First Received: | August 9, 2006 |
| Last Updated: | August 28, 2009 |
| ClinicalTrials.gov Identifier: | NCT00362843 History of Changes |
| Health Authority: | United States: Federal Government |
|
Brain Mapping Positron Emission Tomograhy FMRP (fragile X mental retardation protein) Mental Retardation Neurodevelopmental Disorders |
Cerebral Protein Synthesis Propofol PET Fragile X Fragile X Syndrome |
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Mental Retardation Heredodegenerative Disorders, Nervous System Genetic Diseases, Inborn X-linked Mental Retardation and Macro-orchidism Genetic Diseases, X-Linked Chromosome Disorders |
Neurologic Manifestations Fragile X Syndrome Propofol Congenital Abnormalities Mental Retardation, X-Linked Neurobehavioral Manifestations |
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Disease Nervous System Diseases Chromosome Disorders Fragile X Syndrome Mental Retardation Pathologic Processes Heredodegenerative Disorders, Nervous System Genetic Diseases, Inborn |
Syndrome Genetic Diseases, X-Linked Neurologic Manifestations Sex Chromosome Disorders Mental Retardation, X-Linked Congenital Abnormalities Neurobehavioral Manifestations |
