Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants
This study is currently recruiting participants.
Verified June 2012 by Children's Research Institute
Sponsor:
Children's Research Institute
Collaborator:
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Children's Research Institute
ClinicalTrials.gov Identifier:
NCT01624311
First received: June 13, 2012
Last updated: June 18, 2012
Last verified: June 2012
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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:
Genetics Home Reference related topics:
argininosuccinic aciduria
carbamoyl phosphate synthetase I deficiency
citrullinemia
methylmalonic acidemia
N-acetylglutamate synthase deficiency
ornithine transcarbamylase deficiency
ornithine translocase deficiency
succinic semialdehyde dehydrogenase deficiency
U.S. FDA Resources
Further study details as provided by Children's Research Institute:
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:
|
|
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:
|
Eligibility| Ages Eligible for Study: | up to 2 Months |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Newborns >36 wks gestation and ≥2200g birth weight and young infants up to 2 months of age both 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01624311
Contacts
| Contact: Uta Lichter-Konecki, MD, PhD | 202-476-5000 | ulichter@childrensnational.org |
| Contact: Geneticist On Call, MD | 202-476-5000 |
Locations
| United States, District of Columbia | |
| Children's National Medical Center | Recruiting |
| Washington, District of Columbia, United States, 20010 | |
| Contact: Uta Lichter-Konecki, MD, PhD 202-476-5000 ulichter@childrensnational.org | |
| Contact: Geneticist On Call, MD 202-476-5000 | |
| Principal Investigator: Uta Lichter-Konecki, MD, PhD | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104-4399 | |
| Contact: Vijay Srinivasan, MD 800-879-2467 SRINIVASAN@email.chop.edu | |
| Principal Investigator: Vijay Srinivasan, MD | |
Sponsors and Collaborators
Children's Research Institute
Children's Hospital of Philadelphia
Investigators
| Principal Investigator: | Uta Lichter-Konecki, MD, PhD | Children's Research Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Children's Research Institute |
| ClinicalTrials.gov Identifier: | NCT01624311 History of Changes |
| Other Study ID Numbers: | Pro00000259 |
| Study First Received: | June 13, 2012 |
| Last Updated: | June 18, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Children's Research Institute:
|
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 |
Additional relevant MeSH terms:
|
Hypothermia Urea Cycle Disorders, Inborn Hyperammonemia 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 Pathologic Processes |
ClinicalTrials.gov processed this record on May 16, 2013