Clinical trial NCT01624311: Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants
Official title: Hypothermia Treatment in Hyperammonemia and Encephalopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urea Cycle Disorders
Organic Acidemias
Keywords: High ammonia level
Hyperammonemia
Poor suck
Lethargy
Coma
Encephalopathy
Seizures
Brain edema
Urea Cycle Disorder
Ornithine Transcarbamylase Deficiency
Carbamoyl Phosphate Synthetase Deficiency
Citrullinemia
Argininosuccinic Aciduria
Organic Acidemia
Propionic Aciduria
Methylmalonic Aciduria
Isovaleric Aciduria
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Children's National Research Institute
name: Medical College of Wisconsin
First posted: 2012-06-20
Enrollment: 5
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability
timeFrame: Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks
measure: Feasibility of hypothermia therapy as adjunct therapy to the complex standard of care therapy
timeFrame: During the first 72h of treatment
Secondary outcomes:
measure: Time to normalization of ammonia level
timeFrame: During the first 72 hours of treatment
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: New York
country: United States
facility: Columbia University, Morgan Stanley Children's Hospital
state: New York
city: Milwaukee
country: United States
facility: Medical College Wisconsin
state: Wisconsin
Study officials:
affiliation: Columbia University
name: Uta Lichter-Konecki, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: