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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Columbia University
Sponsor:
Collaborators:
Children's Research Institute
Medical College of Wisconsin
Information provided by (Responsible Party):
Uta Lichter-Konecki, Columbia University
ClinicalTrials.gov Identifier:
NCT01624311
First received: June 13, 2012
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Urea Cycle Disorders
Organic Acidemias
Other: Therapeutic Hypothermia
Other: Standard of care therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hypothermia Treatment in Hyperammonemia and Encephalopathy

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Feasibility of hypothermia therapy as adjunct therapy to the complex standard of care therapy [ Time Frame: During the first 72h of treatment ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Time to normalization of ammonia level [ Time Frame: During the first 72 hours of treatment ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: August 2007
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjunct Hypothermia Arm
Patients that receive adjunct hypothermia in addition to standard of care therapy
Other: 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.
Other Names:
  • Hypothermia
  • Hypothermia therapy
  • Cooling
Historic Controls
Patients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years.
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.
Other Names:
  • Dialysis
  • Hemodialysis
  • CVVH
  • CVVHD

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624311

Contacts
Contact: Uta Lichter-Konecki, MD, PhD 212-305-6731 ul2118@cumc.columbia.edu

Locations
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: An Massaro, MD    202-476-5448    ANguyenM@childrensnational.org   
Contact: , MD         
Sub-Investigator: An Massaro, MD         
United States, New York
Columbia University, Morgan Stanley Children's Hospital Recruiting
New York, New York, United States, 10027
Contact: Uta Lichter-Konecki, MD, PhD    212-305-6731    ul2118@cumc.columbia.edu   
Principal Investigator: Uta Lichter-Konecki, MD PhD         
United States, Wisconsin
Medical College Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: David Dimmok, MD    414-266-2979    ddimmock@mcw.edu   
Contact: Michael Meyer, MD    (414) 266-3360    mtmeyer@mcw.edu   
Sponsors and Collaborators
Uta Lichter-Konecki
Children's Research Institute
Medical College of Wisconsin
Investigators
Principal Investigator: Uta Lichter-Konecki, MD, PhD Columbia University
  More Information

Additional Information:
No publications provided

Responsible Party: Uta Lichter-Konecki, MD, Columbia University
ClinicalTrials.gov Identifier: NCT01624311     History of Changes
Other Study ID Numbers: Pro00000259
Study First Received: June 13, 2012
Last Updated: September 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Coma
High ammonia level
Hyperammonemia
Poor suck
Lethargy
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

Additional relevant MeSH terms:
Hypothermia
Urea Cycle Disorders, Inborn
Body Temperature Changes
Signs and Symptoms
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on October 19, 2014