Urea Cycle DisordersPhase 2NCT01624311
Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants
A Phase 2 study testing Therapeutic Hypothermia in people with Urea Cycle Disorders and Organic Acidemias, run by Uta Lichter-Konecki at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 30 days
- Conditions the study is for
- Urea Cycle Disorders, Organic Acidemias
- What is being tested?
- Therapeutic Hypothermia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2007to May 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 30 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Medical College Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University, Morgan Stanley Children's Hospital
New York, New York, 10027
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Hypothermia Treatment in Hyperammonemia and Encephalopathy
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.
Read the 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.
- Conditions
- Urea Cycle Disorders, Organic Acidemias
- Being tested
- Therapeutic Hypothermia, Standard of Care Therapy
- 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
- Medical subject headings
- Urea Cycle Disorders, Inborn, Hyperammonemia, Lethargy, Coma, Brain Diseases, Seizures, Brain Edema, Ornithine Carbamoyltransferase Deficiency Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic HypothermiaOther
Also called Hypothermia, Hypothermia Therapy, Cooling
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.
Standard of Care TherapyOther
Also called Dialysis, Hemodialysis, CVVH, CVVHD
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.
| Study group | Role | What they receive |
|---|---|---|
| Adjunct Hypothermia Arm | Experimental | Patients that receive adjunct therapeutic hypothermia in addition to standard of care therapy Receives: 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. Receives: Other: Standard of Care Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: During the first 72h of treatment
Secondary outcomes (1)
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.
Measured: During the first 72 hours of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2012 (estimated)
- Study startAug 2007
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urea Cycle DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uta Lichter-Konecki
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Uta Lichter-Konecki, Columbia University
- Investigators
- Uta Lichter-Konecki, MD, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01624311
- Sponsor's protocol ID
- AAAN6104
- Status last verified
- May 2015
- First submitted
- 13 Jun 2012
- Last updated
- 1 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypothermia Treatment in Hyperammonemia and Encephalopathy
- ClinicalTrials.gov ID
- NCT01624311
- Acronym / sponsor ID
- AAAN6104
- Conditions
- Urea Cycle Disorders, Organic Acidemias
- Keywords
- High ammonia level, Hyperammonemia, Poor suck, Lethargy, Coma, Encephalopathy, Seizures, Brain edema
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Uta Lichter-KoneckiUniversity, hospital or other
- Collaborators
- Children's National Research Institute, Medical College of Wisconsin
- Study start
- Aug 2007
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 20 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adjunct Hypothermia Arm | Experimental | Other: Therapeutic HypothermiaPatients that receive adjunct therapeutic hypothermia in addition to standard of care therapy |
| Historic Controls | Other | Other: Standard of Care TherapyPatients that were treated with standard of care therapy for the same conditions at the sponsoring institution over the past 10 years. |
Who may qualify
- Ages
- 1 day to 30 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Therapeutic HypothermiaAlso: Hypothermia, Hypothermia Therapy, CoolingAfter 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 | Adjunct Hypothermia Arm |
| Standard of Care TherapyAlso: Dialysis, Hemodialysis, CVVH, CVVHDPatients 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 | Historic Controls |
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.
1 secondary outcome
Time to normalization of ammonia level
Time frame: During the first 72 hours of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2015.
- National Urea Cycle Disorders Foundation (Family Organisation)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Uta Lichter-Konecki, MD, PhD principal investigator
Columbia University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Therapeutic Hypothermia in people with Urea Cycle Disorders and Organic Acidemias, run by Uta Lichter-Konecki at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2015.