phenylacetic acid and Intracranial Hypertension studies

phenylacetic acid : A monocarboxylic acid that is toluene in which one of the hydrogens of the methyl group has been replaced by a carboxy group.

Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including HYDROCEPHALUS; BRAIN EDEMA; intracranial masses; severe systemic HYPERTENSION; PSEUDOTUMOR CEREBRI; and other disorders.

Research Excerpts

Excerpt	Relevance	Reference
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	7.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	3.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)

Research

Studies (1)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change in Ammonia

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (100.00)	29.6817
2010's	0 (0.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Ytrebø, LM	1
Kristiansen, RG	1
Maehre, H	1
Fuskevåg, OM	1
Kalstad, T	1
Revhaug, A	1
Cobos, MJ	1
Jalan, R	1
Rose, CF	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 2a Study to Evaluate the Safety and Tolerability of OCR-002 (Ornithine Phenylacetate) in the Treatment of Patients With Acute Liver Failure/Severe Acute Liver Injury[NCT01548690]	Phase 2	47 participants (Actual)	Interventional	2012-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To evaluate the effect of OCR-002 on ammonia levels in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: Baseline and 72 Hours

Measurement of OCR-002 Plasma Concentration

Intervention	Percent Change (Mean)
Maximum Dose Level 3.33 g/24h	41.2
Maximum Dose Level 6.65 g/24h	16.6
Maximum Dose Level 10 g/24h	41.8
Maximum Dose Level 20g/24h	38.4

To evaluate the steady state pharmacokinetic and pharmacodynamic profile of OCR-002 in patients with impaired and intact renal function using urinary phenylacetylglutamine (PAGN) as a surrogate marker (NCT01548690)
Timeframe: 24 Hours after last infusion

Neurological Function Measured by the Orientation Log (O-log)

Intervention	micrograms per millileter (Mean)
Maximum Dose Level 3.33 g/24h	65.6
Maximum Dose Level 6.65 g/24h	32.2
Maximum Dose Level 10 g/24h	33.4
Maximum Dose Level 20g/24h	104.9

The orientation log focuses on orientation to place, time, and circumstance. There are 10 items on the orientation log, which are scored 0-3. A spontaneous correct response is awarded 3 points. A spontaneous response that is lacking or incorrect, but a correct response is provided following a logical cue is awarded 2 points. A score of 1 is given if spontaneous and cued responses are lacking or incorrect, but a correct response is provided in a recognition format. A score of 0 is given if the spontaneous, cued, or recognition format does not generate a correct answer. Scores from the 10 items are summed and the final score ranges from 0 to 30. (NCT01548690)
Timeframe: 30 Days

Neurological Function Measured by the West Haven Criteria (WHC) for Hepatic Encephalopathy

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	23.8
Maximum Dose Level 6.65 g/24h	24.0
Maximum Dose Level 10 g/24h	24.0
Maximum Dose Level 20g/24h	24.0

The West Haven Criteria (WHC) for Hepatic Encephalopathy measures the severity of encephalopathy and patient's level of consciousness. The scale ranges from 0 to 4; a minimum score of 0 represents a better outcome, and a maximum total score of 4 represents a worse outcome. A score of 0 corresponds to normal consciousness and behavior and normal neurological examination. A score of 1 corresponds to mild lack of awareness, shortened attention span, and impaired addition or subtraction; mild asterixis or tremor. A score of 2 corresponds to lethargy, disorientated or inappropriate behavior, obvious asterixis; slurred speech. A score of 3 corresponds to somnolent but arousable, gross disorientation or bizarre behavior, muscle rigidity and clonus; hyperreflexia. A score of 4 corresponds to coma and decerebrate posturing. (NCT01548690)
Timeframe: 120 hours from start of infusion

Number of Participants That do Not Tolerate the Administered Dose and Had Grade 3 or 4 Treatment Emergent Adverse Events as a Measure of Safety and Tolerability

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	2.4
Maximum Dose Level 6.65 g/24h	3.2
Maximum Dose Level 10 g/24h	1.6
Maximum Dose Level 20g/24h	1.8

To evaluate the safety and tolerability of OCR-002 in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: 30 Days

phenylacetic acid and Intracranial Hypertension