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NCT Number: NCT01624311

Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants

This is a pilot study which will test the safety and feasibility of hypothermia treatment as adjunct therapy to conventional treatment of hyperammonemic encephalopathy (HAE) in neonates versus conventional treatment (dialysis, nutritional therapy, and ammonia scavenging drugs) only. The endpoint of the pilot study will be reached when either 24 patients have been enrolled and no serious adverse events were observed, when no patient has been enrolled in 5 years, or when serious adverse events occur which are clearly linked to the use of hypothermia. These would be serious complications not seen in patients on conventional therapy (dialysis , nutritional therapy, ammonia scavenging drugs) for HAE.

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Key information

Conditions

Urea Cycle Disorders Amino Acid Metabolism, Inborn Errors Argininosuccinic Aciduria Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Brain Edema Carbamoyl-Phosphate Synthase I Deficiency Disease Central Nervous System Diseases Citrullinemia Coma Congenital, Hereditary, and Neonatal Diseases and Abnormalities Consciousness Disorders Genetic Diseases, Inborn Genetic Diseases, X-Linked Hyperammonemia Lethargy Metabolic Diseases Metabolism, Inborn Errors Methylmalonic acidemia Mitochondrial Diseases Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutritional and Metabolic Diseases Organic Acidemias Ornithine Carbamoyltransferase Deficiency Disease Pathologic Processes Pathological Conditions, Signs and Symptoms Propionic Acidemia Seizures Signs and Symptoms Unconsciousness Urea Cycle Disorders, Inborn

Age range

1 day–30 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Children's National Medical Center, Washington D.C., District of Columbia, United States

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About this study

Children with neonatal onset Urea Cycle Disorders or Organic Acidemias develop hyperammonemia (high ammonia levels) and fall into coma often causing brain damage. For these children to be able to benefit maximally from available long-term treatment and solid organ transplant, outcome of the neonatal onset crisis must be improved. Animal experiments and small clinical trials have indicated that hypothermia protects the brain during hyperammonemia. This pilot study investigates whether adjunct hypothermia therapy in addition to standard of care treatment is feasible and safe in babies with high ammonia levels in coma.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Newborns >36 wks gestation and ≥2200g birth weight without co-morbidity (see exclusion criteria) that have clinical signs and symptoms of an Urea Cycle Disorders or Propionic , Methylmalonic, or Isovaleric acidemia and hyperammonemia and encephalopathy requiring renal replacement therapy.

Exclusion criteria

  • Patients with hyperammonemia that have clinical signs and symptoms of lysinuric protein intolerance, mitochondrial disorders, congenital lactic acidosis, and fatty acid oxidation disorders, patients with rare and unrelated serious comorbidities and other genetic diseases, e.g., Down syndrome, intraventricular hemorrhage in the newborn period, traumatic brain injury, and low birth weight (<2,200 g at >36 wks gestation).
  • Infants in extremis for which no additional intensive therapy will be offered by the attending neonatologist.

Treatment and study plan

Therapeutic hypothermia

Other

After obtaining written consent, patients are cooled to 33.5°C (+/- 1°C ) for 72 hours and and then rewarmed by 0.5°C per every 3 hours over 18 hours.

Other names: Hypothermia, Hypothermia Therapy, Cooling

Standard of Care Therapy

Other

Patients with hyperammonemia and encephalopathy requiring renal replacement therapy due to a urea cycle disorder or organic acidemia that were treated at Children's National Medical Center over the past 10 years.

Other names: Dialysis, Hemodialysis, CVVH, CVVHD

Primary outcomes

  1. Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability

    Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks

    The DSMB meets within 3 weeks of each case, no later than 5 weeks after initiation of hypothermia therapy and assesses the safety and feasibility of adjunct hypothermia treatment in this patient group. The treatment of neonates and very young infants in hyperammonemic coma is very complex and adding hypothermia therapy to this treatment could not be feasible, the pilot study therefore also assesses the feasibility of adding hypothermia therapy to the standard of care treatment.

  2. Feasibility of hypothermia therapy as adjunct therapy to the complex standard of care therapy

    Time frame: During the first 72h of treatment

    The standard of care therapy is very complex. It includes renal replacement therapy, metabolic diet intervention, and ammonia scavenger use. The pilot study will assess primarily for the first 72 hours of treatment and secondarily for the duration of the hospital stay, an expected average of 5 weeks, whether adding hypothermia to this already complex treatment is feasible.

Secondary outcomes

  1. Time to normalization of ammonia level

    Time frame: During the first 72 hours of treatment

    One of the effects of hypothermia treatment is an overall slowing of metabolism which should cause less ammonia to be produced. If this is correct this should lead to a faster normalization of the ammonia level by renal replacement therapy.

Sponsors and collaborators

Lead sponsor

Uta Lichter-Konecki

Other

Collaborators

  • Children's National Research Institute
  • Medical College of Wisconsin

Registry information

Official study title

Hypothermia Treatment in Hyperammonemia and Encephalopathy

Important dates

Study start
2007
Primary completion
2015
Study completion
2015
First posted
Jun 20, 2012
Registry last updated
Jun 1, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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