Clinical Trial: Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI

Brief Summary: The purpose of this study is to use various types of MRI and cognitive testing to evaluate changes in the brain and cognitive function that occur in subjects with ornithine transcarbamylase deficiency (OTCD) relative to healthy individuals

Detailed Summary:

The overall goal of this project is to characterize metabolic, structural and cognitive changes in OTCD using 1H MRS, DTI, volumetric averaging and fMRI with cognitive testing of executive function measures to validate biomarkers for the effect of HA and its treatment on the brain.

The investigators will measure gln and mI in blood and brain (using 1H MRS) in affected participants, and mI in brain in controls, fractional anisotropy as a measure of white matter microstructural damage (by DTI) and brain activation pathways alterations with tasks probing working memory (fMRI). As a secondary outcome measure, the investigators will correlate the findings from neuroimaging with cognitive functioning. This protocol is based on the previous 5104 protocol, now includes children to evaluate the age and stage of disease on these indices in a cohort that is undergoing important developmental events against an age matched typically developing cohort.


Sponsor: Andrea Gropman

Current Primary Outcome:

  • Concentration of Glutamine and Myoinositol [ Time Frame: Baseline ]

    Concentration based on area under curve on 1H Magnetic Resonance Spectroscopy(MRS) and quantitated by LCModel (a method that allows automatic quantitation of spectroscopy data). A metabolite's tissue concentration is related to the integrated amplitude, the area under the curve of the MRS signal, it produces. While MRS signals are usually acquired in the time domain as free induction decays or echoes, they are usually viewed and analyzed in the frequency domain. The frequency domain representation is derived from the acquired time domain data by the Fourier Transform. The protocol we use selects 257 averages. The machine summates the data at each time point to generate one value for the area under the curve. Therefore, we don't have the measurement at each time point.

    Furthermore, we measured voxels in two different brain areas containing different kinds of brain matter: one voxel was located in posterior cingulate gray matter (PCGM) and the other in parietal white matter (PWM).

  • Functional Connectivity of Assessed by Resting-state fMRI [ Time Frame: Baseline ]
    Investigation of differences in functional connectivity of OTCD patients compared to healthy controls, particularly in the default-mode network (DMN) and the set-maintenance network (SMN). Participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, identified the nodes that comprised each network in each group, and assessed internodal connectivity. For each subject, this analysis generated a correlation value, whic

    Original Primary Outcome: Biomarker characterization [ Time Frame: Baseline ]

    To characterize metabolic, structural and cognitive changes in OTCD by 1H MRS, DTI, volumetric measures, and fMRI and to validate biomarkers for the effect of HA and its treatment on the brain.


    Current Secondary Outcome: Neuropsychological Assessment [ Time Frame: Baseline ]

    Testing consisted of the Wechsler Abbreviated Scale of Intelligence (WASI), Comprehensive Trail Making Test (CTMT) (range 17-87), and the Behavioral Rating Inventory of Executive Function (BRIEF) (range GEC: 70-210; BRI:39-82 ; MI:41-92). The WASI includes three measures of intelligence; including, performance IQ (sum of block design and matrices sub scales; range: 40-160), verbal IQ (sum of vocabulary and similarities sub scales; range 40-160), and total IQ (sum of all four subscales; range: 80-320). The CTMT measures simple attention and executive function, it consists of five dot to dots that increase with complexity and difficulty. Higher values indicate better outcomes for all scales.


    Original Secondary Outcome: Correlation of imaging markers with cognitive function [ Time Frame: Baseline ]

    To correlate the findings from neuroimaging with cognitive functioning and clinical parameters.


    Information By: Children's Research Institute

    Dates:
    Date Received: March 30, 2012
    Date Started: September 2010
    Date Completion:
    Last Updated: April 12, 2017
    Last Verified: April 2017