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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Hypothermia Treatment in Hyperammonemia and Encephalopathy

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 Summary: 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.
Sponsor: Uta Lichter-Konecki

Current Primary Outcome:

  • 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 ]
    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 ]
    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.


Original Primary Outcome: Same as current

Current Secondary Outcome: Time to normalization of ammonia level [ Time Frame: 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.


Original Secondary Outcome: Same as current

Information By: Columbia University

Dates:
Date Received: June 13, 2012
Date Started: August 2007
Date Completion:
Last Updated: May 28, 2015
Last Verified: May 2015