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Neurologic Injuries in Adults With Urea Cycle Disorders

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ClinicalTrials.gov Identifier: NCT00472732
Recruitment Status : Completed
First Posted : May 14, 2007
Results First Posted : May 29, 2015
Last Update Posted : June 24, 2015
Sponsor:
Collaborators:
Office of Rare Diseases (ORD)
Rare Diseases Clinical Research Network
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Andrea Gropman, Children's Research Institute

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Conditions Brain Diseases, Metabolic, Inborn
Urea Cycle Disorder
Ornithine Transcarbamylase Deficiency
Enrollment 46
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD Healthy Males or Females Without Known Medical or Metabolic di
Hide Arm/Group Description Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD Healthy males or females without known medical or metabolic disorder (control group)
Period Title: Overall Study
Started 24 22
Completed 24 22
Not Completed 0 0
Arm/Group Title Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD Healthy Males or Females Without Known Medical or Metabolic di Total
Hide Arm/Group Description Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD Healthy males or females without known medical or metabolic disorder (control group) Total of all reporting groups
Overall Number of Baseline Participants 24 22 46
Hide Baseline Analysis Population Description
Half of the subjects were affected and half were normal controls age 18-60
Age, Customized  
Mean (Full Range)
Unit of measure:  Years
Age Number Analyzed 24 participants 22 participants 46 participants
32.55
(18 to 58)
32.38
(18 to 59)
32.46
(18 to 59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Female
17
  70.8%
19
  86.4%
36
  78.3%
Male
7
  29.2%
3
  13.6%
10
  21.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Hispanic or Latino
1
   4.2%
1
   4.5%
2
   4.3%
Not Hispanic or Latino
23
  95.8%
21
  95.5%
44
  95.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   4.2%
2
   9.1%
3
   6.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
5
  22.7%
5
  10.9%
White
23
  95.8%
15
  68.2%
38
  82.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants 22 participants 46 participants
24 22 46
1.Primary Outcome
Title Concentration of Glutamine and Myoinositol by MRS
Hide Description

Concentration based on area under curve on 1H MRS and quantitated by LCModel. A metabolite’s tissue concentration is related to the integrated amplitude of the MRS signal it produces. Integrated amplitude is the area under the MRS signal curve. 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. This means, 257 free induction decays. 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).

Time Frame one time measurement at study baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title OTCD Patients Healthy Controls
Hide Arm/Group Description:
Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD
Healthy males or females without known medical or metabolic disorder (control group)
Overall Number of Participants Analyzed 24 22
Mean (Standard Deviation)
Unit of Measure: mM
Glutamine in PCGM 4.97  (2.08) 3.66  (1.36)
Myoinositol in PCGM 3.78  (0.82) 4.50  (0.43)
Glutamine in PWM 2.13  (1.22) 1.09  (0.75)
Myoinositol in PWM 2.27  (0.77) 2.86  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments The null hypothesis predicted that the concentration of myoinositol in posterior cingulate gray matter will be the same in OTCD patients as in controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments The Bonferroni-corrected a priori p-value was 0.007 (a priori alpha=0.05/number of tests=7).
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments The null hypothesis predicted that the concentration of myoinositol in parietal white matter will be the same in OTCD patients as in controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Bonferroni-corrected a priori p-value was 0.007 (a priori alpha=0.05/number of tests=7).
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments The null hypothesis predicted that the concentration of glutamine in posterior cingulate gray matter would be the same for OTCD patients as for controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments The Bonferroni-corrected a priori p-value was 0.007 (a priori alpha=0.05/number of tests=7).
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments The null hypothesis predicted that the concentration of glutamine in parietal white matter would be the same for OTCD patients as for controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Bonferroni-corrected a priori p-value was 0.007 (a priori alpha=0.05/number of tests=7).
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Functional MRI Activation in N-Back Tast
Hide Description Measure of blood oxygen level dependent (BOLD) signal of OTCD patients and healthy controls during an N-Back task comparing 2-back and 1-back conditions. This contrast was created for each participant using SPM and then entered into a group analysis in which we compare percent signal change between groups. Therefore, we never see BOLD signal change at the individual level, which is why we never see "scores" or numbers at the individual level and we cannot calculate a measure of dispersion for this data.
Time Frame one time measurement at study baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Five OTCD patients and one healthy control were excluded due to excessive head motion.
Arm/Group Title OTCD Patients Healthy Controls
Hide Arm/Group Description:
Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD
Healthy males or females without known medical or metabolic disorder (control group)
Overall Number of Participants Analyzed 19 21
Measure Type: Number
Unit of Measure: percent signal change
Dorsolateral prefrontal cortex (BA 10) 0.21 0.04
Dorsolateral prefrontal cortex (BA 46) 0.22 0.15
Anterior cingulate cortex (BA 32) 0.515 0.28
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments Two-way between-group t-tests restricted to the prefrontal cortex were performed to compare activation during for the 2-Back> 1-Back contrast between OTCD patients and controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments This p-value is adjusted for family wise error rate correction.
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Fractional Anisotropy
Hide Description Measure of white matter integrity in OTCD Patients and Controls in frontal white matter. Fractional anisotropy values fall on a scale of 0 to 1, with 0 meaning that the diffusion of water is isotropic and unrestricted, or equally restricted, in all directions and with 1 meaning that diffusion occurs along only one axis and is fully restricted along all other directions. Scores closer to 1 are associated with intact white matter while scores closer to 0 are associated with white matter damage.
Time Frame one time measurement at study baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Five OTCD Patients and four healthy controls were excluded due to excessive head motion.
Arm/Group Title OTCD Patients Healthy Controls
Hide Arm/Group Description:
Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD
Healthy males or females without known medical or metabolic disorder (control group)
Overall Number of Participants Analyzed 19 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.247  (0.016) 0.274  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OTCD Patients, Healthy Controls
Comments The null hypothesis predicted that fractional anisotropy, a marker of white matter integrity, would be the same for OTCD patients as for controls.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Entire study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OTCD Patients Healthy Controls
Hide Arm/Group Description Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD Healthy males or females without known medical or metabolic disorder (control group)
All-Cause Mortality
OTCD Patients Healthy Controls
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
OTCD Patients Healthy Controls
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/22 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
OTCD Patients Healthy Controls
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/22 (0.00%) 
This study examined the neurobiological differences between OTCD patients and controls. This was, however, not a clinical trial, since participants received no form of drug therapy or treatment as part of this study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Andrea Gropman, M.D.
Organization: Children's Research Institute
Phone: 202-476-2120
Responsible Party: Andrea Gropman, Children's Research Institute
ClinicalTrials.gov Identifier: NCT00472732     History of Changes
Other Study ID Numbers: RDCRN 5104
U54RR019453 ( U.S. NIH Grant/Contract )
First Submitted: May 11, 2007
First Posted: May 14, 2007
Results First Submitted: April 22, 2015
Results First Posted: May 29, 2015
Last Update Posted: June 24, 2015