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

Uta Lichter-Konecki

Status and phase: Completed; Phase 2

Conditions: Urea Cycle Disorders; Organic Acidemias

Treatments: Other: Standard of Care Therapy; Other: Therapeutic Hypothermia

Study type: Interventional

Funder types: Other

Identifiers

NCT01624311

AAAN6104

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 1 to 30 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 2 patient groups

Adjunct Hypothermia Arm

Experimental group

Description:

Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy

Treatment:

Other: Therapeutic Hypothermia

Historic Controls

Other group

Description:

Patients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years.

Treatment:

Other: Standard of Care Therapy