Recruiting

Observational Study

Sponsor:

Children's National Research Institute

Code:

NCT04602325

Conditions

Urea Cycle Disorder

Organic Acidemia

Maple Syrup Urine Disease

Glutaric Acidemia I

Fatty Acid Oxidation Disorder

Eligibility Criteria

Sex: All

Age: 7 - 18

Healthy Volunteers: Not accepted

Study Details

Brief summary:

Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. The following aims are proposed:

Aim 1 of this study will be to determine the chronology of biomarkers of brain injury in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder.

Aim 2 will be to determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).

Conditions

Urea Cycle Disorder

Organic Acidemia

Maple Syrup Urine Disease

Glutaric Acidemia I

Fatty Acid Oxidation Disorder

Study ID

NCT04602325

Start date

Jul 9, 2020

Status verified date

Feb, 2024

Completion date

May, 2027

Anticipated

Primary completion date

Jul, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 7 - 18

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Inherited Hyperammonemias:

1. A clinical diagnosis of 1 of 7 diagnosed urea cycle disorders:

  • N-acetylglutamate Synthetase Deficiency (NAGS)
  • Carbamyl Phosphate Synthetase Deficiency (CPSD)
  • Ornithine Transcarbamylase Deficiency (OTCD)
  • Argininosuccinate Synthetase Deficiency (ASD)
  • Argininosuccinate Lyase Deficiency (ALD)
  • Arginase Deficiency (AD)
  • Hyperammonemia-Hyperornithinemia-Homocitrullinuria (HHH)
2. A clinical diagnosis of 1 of 2 organic acidemias:

  • Propionic Acidemia (PA)
  • Methylmalonic Acidemia (MMA)
2. Acute metabolic disorder without hyperammonemia, with neurological sequelae

1. Maple Syrup Urine Disease (MSUD)
2. Glutaric Acidemia (GA1)
3. Acute metabolic disorder without hyperammonemia and without neurological sequelae

  • Fatty Acid Oxidation Disorders:
  • Medium Chain-Acyl CoA Dehydrogenase Deficiency
  • Very Long Chain-Acyl CoA Dehydrogenase Deficiency
  • Trifunctional Protein Deficiency
  • Long Chain Hydroxyacyl-CoA Dehydrogenase Deficiency
  • Carnitine Palmitoyltransferase I or II Deficiency
  • Carnitine/Acylcarnitine Translocase Deficiency
  • Primary Carnitine Transport Deficiency
4. Hypoxic-Ischemic Encephalopathy

Exclusion Criteria:

  • Prior Solid-Organ Transplant
  • Use of any other investigational drug, biologic, or therapy or any clinical or laboratory abnormality or medical condition that, as determined by the investigator, may interfere with or obscure the biomarker measurements

Study Design

Enrollment

24 participants

Anticipated

Interventions and Outcome Measures

Arms

Inherited Hyperammonemias

A clinical diagnosis of 1 of 7 diagnosed urea cycle disorders:

1. N-acetylglutamate Synthetase Deficiency (NAGS)
2. Carbamyl Phosphate Synthetase Deficiency (CPSD)
3. Ornithine Transcarbamylase Deficiency (OTCD)
4. Argininosuccinate Synthetase Deficiency (ASD)
5. Argininosuccinate Lyase Deficiency (ALD)
6. Arginase Deficiency (AD)
7. Hyperammonemia-Hyperornithinemia-Homocitrullinuria (HHH)

A clinical diagnosis of 1 of 2 organic acidemias:

1. Propionic Acidemia (PA)
2. Methylmalonic Acidemia (MMA)

Acute Metabolic Disorder + Neurological Sequelae

Acute metabolic disorder without hyperammonemia but with neurological sequelae:

1. Maple Syrup Urine Disease (MSUD)
2. Glutaric Acidemia (GA1)

Fatty Acid Oxidation Disorders

Acute metabolic disorder without hyperammonemia and without neurological sequelae:

1. Medium Chain-Acyl CoA Dehydrogenase Deficiency
2. Very Long Chain-Acyl CoA Dehydrogenase Deficiency
3. Trifunctional Protein Deficiency
4. Long Chain Hydroxyacyl-CoA Dehydrogenase Deficiency
5. Carnitine Palmitoyltransferase I or II Deficiency
6. Carnitine/Acylcarnitine Translocase Deficiency
7. Primary Carnitine Transport Deficiency

Hypoxic-Ischemic Encephalopathy

Patients with hypoxic-ischemic encephalopathy

Primary outcome measure

  • Biomarker Brain Injury Chronology [ Time Frame: 2 Years ]

Central Contacts and Locations

Central contacts

Katie Rice, MPH, CCRP

202-476-6191krice3@childrensnational.org

Nicholas Ah Mew, MD

202-476-5863nahmew@childrensnational.org

Locations

Children's National Research Institute

Recruiting

Washington, District of Columbia, United States, 20010

Contacts

Katie Rice, MPH, CCRP

krice3@childrensnational.org

Principal Investigator:

Nicholas Ah Mew, MD

More Information

Sponsor

Children's National Research Institute

Last update posted

Feb 7, 2024

Last verified

Feb, 2024

Keywords

  • N-acetylglutamate Synthetase Deficiency
  • Carbamyl Phosphate Synthetase Deficiency
  • Ornithine Transcarbamylase Deficiency
  • Argininosuccinate Synthetase Deficiency
  • Argininosuccinate Lyase Deficiency
  • Arginase Deficiency
  • Hyperammonemia-Hyperornithinemia-Homocitrullinuria
  • Medium Chain-Acyl CoA Dehydrogenase Deficiency
  • Very Long Chain-Acyl CoA Dehydrogenase Deficiency
  • Trifunctional Protein Deficiency
  • Long Chain Hydroxyacyl-CoA Dehydrogenase Deficiency
  • Carnitine Palmitoyltransferase I or II Deficiency
  • Carnitine/Acylcarnitine Translocase Deficiency
  • Primary Carnitine Transport Deficiency

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Children's National Research Institute on 2024-02-07.