Trial Outcomes & Findings for Neurologic Injuries in Adults With Urea Cycle Disorders (NCT NCT00472732)

Last Updated: 2015-06-24

Results Overview

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).

Recruitment status

COMPLETED

Target enrollment

46 participants

Primary outcome timeframe

one time measurement at study baseline

Results posted on

2015-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD	Healthy Males or Females Without Known Medical or Metabolic di Healthy males or females without known medical or metabolic disorder (control group)
Overall Study STARTED	24	22
Overall Study COMPLETED	24	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neurologic Injuries in Adults With Urea Cycle Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Female Carriers of Ornithine Transcarbamylase Deficiency (OTCD n=24 Participants Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD	Healthy Males or Females Without Known Medical or Metabolic di n=22 Participants Healthy males or females without known medical or metabolic disorder (control group)	Total n=46 Participants Total of all reporting groups
Age, Customized Age	32.55 years n=5 Participants	32.38 years n=7 Participants	32.46 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	15 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	22 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: one time measurement at study baseline

Outcome measures

Outcome measures
Measure	OTCD Patients n=24 Participants Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD	Healthy Controls n=22 Participants Healthy males or females without known medical or metabolic disorder (control group)
Concentration of Glutamine and Myoinositol by MRS Myoinositol in PCGM	3.78 mM Standard Deviation 0.82	4.50 mM Standard Deviation 0.43
Concentration of Glutamine and Myoinositol by MRS Glutamine in PWM	2.13 mM Standard Deviation 1.22	1.09 mM Standard Deviation 0.75
Concentration of Glutamine and Myoinositol by MRS Glutamine in PCGM	4.97 mM Standard Deviation 2.08	3.66 mM Standard Deviation 1.36
Concentration of Glutamine and Myoinositol by MRS Myoinositol in PWM	2.27 mM Standard Deviation 0.77	2.86 mM Standard Deviation 0.38

PRIMARY outcome

Timeframe: one time measurement at study baseline

Population: Five OTCD patients and one healthy control were excluded due to excessive head motion.

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.

Outcome measures

Outcome measures
Measure	OTCD Patients n=19 Participants Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD	Healthy Controls n=21 Participants Healthy males or females without known medical or metabolic disorder (control group)
Functional MRI Activation in N-Back Tast Dorsolateral prefrontal cortex (BA 10)	0.21 percent signal change	0.04 percent signal change
Functional MRI Activation in N-Back Tast Dorsolateral prefrontal cortex (BA 46)	0.22 percent signal change	0.15 percent signal change
Functional MRI Activation in N-Back Tast Anterior cingulate cortex (BA 32)	0.515 percent signal change	0.28 percent signal change

PRIMARY outcome

Timeframe: one time measurement at study baseline

Population: Five OTCD Patients and four healthy controls were excluded due to excessive head motion.

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.

Outcome measures

Outcome measures
Measure	OTCD Patients n=19 Participants Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD	Healthy Controls n=18 Participants Healthy males or females without known medical or metabolic disorder (control group)
Fractional Anisotropy	0.247 units on a scale Standard Deviation 0.016	0.274 units on a scale Standard Deviation 0.015

Adverse Events

OTCD Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Andrea Gropman, M.D.

Children's Research Institute

Phone: 202-476-2120

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place