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

NCT01624311 | Completed Phase 2 DMC

• 1 other identifier: AAAN6104
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Participants will be followed for the duration of the hospital stay, an expected average of 5 weeks

• 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.

  During the first 72h of treatment

Secondary Outcomes (1)

• Time to normalization of ammonia level

  During the first 72 hours of treatment

Study Arms (2)

Adjunct Hypothermia Arm

EXPERIMENTAL

Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy

Other: Therapeutic Hypothermia

Historic Controls

OTHER

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

Interventions

Therapeutic Hypothermia OTHER

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.

Also known as: Hypothermia, Hypothermia Therapy, Cooling

Adjunct Hypothermia Arm

Standard of Care Therapy OTHER

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.

Also known as: Dialysis, Hemodialysis, CVVH, CVVHD

Historic Controls

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uta Lichter-Konecki: lead
• Children's National Research Institute: collaborator
• Medical College of Wisconsin: collaborator

Study Sites (3)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Columbia University, Morgan Stanley Children's Hospital

New York, New York, 10027, United States

Location

Medical College Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• National Urea Cycle Disorders Foundation (Family Organisation)

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Hyperammonemia; Lethargy; Coma; Brain Diseases; Seizures; Brain Edema; Ornithine Carbamoyltransferase Deficiency Disease; Carbamoyl-Phosphate Synthase I Deficiency Disease; Citrullinemia; Argininosuccinic Aciduria; Propionic Acidemia; Methylmalonic acidemia

Interventions

Hypothermia, Induced; Cryotherapy; Cool-Down Exercise; Dialysis; Renal Dialysis; Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Unconsciousness; Consciousness Disorders; Genetic Diseases, X-Linked; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Post-Exercise Recovery Techniques; Physical Therapy Modalities; Rehabilitation; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Chemistry Techniques, Analytical; Investigative Techniques; Chemical Phenomena; Renal Replacement Therapy; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Uta Lichter-Konecki, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 13, 2012
• First Posted: June 20, 2012
• Study Start: August 1, 2007
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 1, 2015

Record last verified: 2015-05

Locations

US (3)