Urea Cycle Disorders, Organic Acidemias
Conditions
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
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.
Interventions
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.
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.
Sponsors
Children's National Research Institute
Medical College of Wisconsin
Uta Lichter-Konecki
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 30 Days
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with unexpected Serious Adverse Events as a Measure of Safety and Tolerability | Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks | 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 | During the first 72h of treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to normalization of ammonia level | During the first 72 hours of treatment | 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. |
Countries
United States
Outcome results
None listed