Fragile X Syndrome (FXS)
Conditions
Keywords
FXS
Brief summary
Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). The investigators wish to examine brain distribution of sigma-1 receptors in young adult males with FXS using 18F-FTC-146 PET. This project will study the distribution of sigma-1 receptors in 15 young (18-30 years) male adults with FXS compared to 5 healthy adult volunteers.
Detailed description
In this study, we measured sigma-1 receptor density in the regions of interest in brain known to be involved in executive functioning and cognition using 18F-FTC-146 PET. We then compared S1R density in areas ROIs not involved in executive functioning and cognition. This provided a framework for predicting functional impairment based on brain-behavior relationships. The study had two aims. The first aim was to evaluate the reliability of 18F-FTC-146 brain uptake in healthy controls under test and retest conditions to establish a baseline measure of S1R density and quantify regional brain uptake of radiotracer in five healthy adults. The second aim was to characterize S1R density in brains of young adult males with FXS which will then be compared to healthy volunteers. This was the very first PET study to image sigma-1 receptor density in participants with fragile X syndrome, thereby testing whether altered receptor density is present in brain in fragile X syndrome patients when compared to healthy volunteers. If confirmed, the current study would have provided compelling clinical-translational support for an important pathophysiological mechanism of cognition and executive function. The study had considerable potential for advancing the neurobiological understanding of fragile X syndrome in humans.
Interventions
DRUG18F-FTC-146
18F-FTC-146 is a PET radiopharmaceutical that can be used to determine sigma-1 receptor density.
Sponsors
Guido A. Davidzon, MD, SM
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
15 male subjects with FXS will be compared to 5 healthy volunteers who will be the control group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for healthy volunteers: 1. Ages 18-65 2. Either gender and all ethno-racial categories 3. Capacity to provide informed consent 4. Female participants are expected to use an effective method of birth control throughout the study which includes: hormonal methods (birth control pills, patches, injections, vaginal ring or implants), barrier method (condom or diaphragm) used with spermicide, intrauterine device (IUD), or abstinence (no sex) 5. Can travel to Stanford for 2 scan days. Inclusion criteria for individuals with FXS: 1. Males who are physically healthy 2. Aged between 18 and 30 years inclusive 3. Can travel to Stanford for a 2-day visit. 4. IQ between 40 and 80 points. 5. Ability to remain seated for more than 10 minutes. 6. Have an established genetic diagnosis of FXS (full mutation with evidence of aberrant methylation of the FMR1 gene, confirmed by genetic testing).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of concordant readings of regional brain uptake of radiotracer [18F]FTC-146 as a measure of reliability under test-retest conditions | Up to 6 hours per scan performed on Day 0 (Test) and Day 7 (Retest) | Regional brain uptake of \[18F\]FTC-146 will be analyzed by kinetic modeling with metabolite-corrected arterial input functions to establish stability and reproducibility of \[18F\] FTC-146 in humans under test and retest conditions. This outcome will be assessed in healthy volunteers only. |
| Difference in Non-displaceable Binding Potential (BPND) of [18F]FTC-146 in fragile X syndrome (FXS) patients relative to healthy volunteers | Up to 6 hours per scan performed on Day 0 (both groups) and Day 7 (healthy volunteers) | Binding potential provides an estimate of the S1R receptor distribution and affinity of \[18F\]FTC-146 to the S1R receptors. Binding potential measurements will be compared between participants with fragile X syndrome and control group with healthy volunteers to assess if there is a difference. Binding Potential (BPND) is estimated as the distribution volume ratio (DVR) -1. DVR's of tracers are used in PET receptor studies where the radiopharmaceutical can be specifically bound to receptors; nonspecifically bound to other macromolecular components, or free in tissue (FT). DVR is calculated using a Logan Plot, which uses the dynamic PET images obtained during imaging and compartment modeling to graphically analyze by linear regression pharmacokinetic data for radiopharmaceuticals that undergo 'reversible' uptake. Healthy volunteers will have scans at Day 0 and Day 7, and FXS patients will have a single scan on day 0. All scans will be analyzed. |
Countries
United States
Outcome results
None listed