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

NCT ID: NCT01624311

Last Updated: 2015-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2015-05-31

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.

Conditions

Urea Cycle Disorders; Organic Acidemias

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjunct Hypothermia Arm

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

Group Type: EXPERIMENTAL

Therapeutic Hypothermia

Intervention Type: 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.

Historic Controls

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

Group Type: OTHER

Standard of Care Therapy

Intervention Type: 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.

Interventions

Therapeutic Hypothermia

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.

Intervention Type: OTHER

Standard of Care Therapy

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.

Intervention Type: OTHER

Other Intervention Names

Hypothermia; Hypothermia Therapy; Cooling; Dialysis; Hemodialysis; CVVH; CVVHD

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 30 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's National Research Institute

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

Uta Lichter-Konecki

OTHER

Sponsor Role: lead

Responsible Party

Uta Lichter-Konecki

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Uta Lichter-Konecki, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Children's National Medical Center

Washington D.C., District of Columbia, United States

Columbia University, Morgan Stanley Children's Hospital

New York, New York, United States

Medical College Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Related Links

http://www.nucdf.org/

National Urea Cycle Disorders Foundation (Family Organisation)

Other Identifiers

AAAN6104

Identifier Type: -

Identifier Source: org_study_id