Back to resultsPilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants
Primary Purpose
Urea Cycle Disorders, Organic Acidemias
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Therapeutic Hypothermia
Standard of Care Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Urea Cycle Disorders focused on measuring 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
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.
Sites / Locations
- Children's National Medical Center
- Columbia University, Morgan Stanley Children's Hospital
- Medical College Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Adjunct Hypothermia Arm
Historic Controls
Arm Description
Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy
Patients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years.
Outcomes
Primary Outcome Measures
Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability
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
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
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.
Full Information
NCT ID
NCT01624311
First Posted
June 13, 2012
Last Updated
May 28, 2015
Sponsor
Uta Lichter-Konecki
Collaborators
Children's National Research Institute, Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT01624311
Brief Title
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
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Uta Lichter-Konecki
Collaborators
Children's National Research Institute, Medical College of Wisconsin
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adjunct Hypothermia Arm
Arm Type
Experimental
Arm Description
Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy
Arm Title
Historic Controls
Arm Type
Other
Arm Description
Patients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years.
Intervention Type
Other
Intervention Name(s)
Therapeutic Hypothermia
Other Intervention Name(s)
Hypothermia, Hypothermia Therapy, Cooling
Intervention Description
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
Intervention Name(s)
Standard of Care Therapy
Other Intervention Name(s)
Dialysis, Hemodialysis, CVVH, CVVHD
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability
Description
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.
Time Frame
Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks
Title
Feasibility of hypothermia therapy as adjunct therapy to the complex standard of care therapy
Description
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.
Time Frame
During the first 72h of treatment
Secondary Outcome Measure Information:
Title
Time to normalization of ammonia level
Description
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.
Time Frame
During the first 72 hours of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
30 Days
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uta Lichter-Konecki, MD, PhD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Columbia University, Morgan Stanley Children's Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10027
Country
United States
Facility Name
Medical College Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.nucdf.org/
Description
National Urea Cycle Disorders Foundation (Family Organisation)
Learn more about this trial
Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants
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