Diabetic KetoacidosisNCT00629707
Cerebral Edema in Pediatric Diabetic Ketoacidosis
A study testing intravenous fluid treatment in people with Diabetic Ketoacidosis, run by University of California, Davis at 1 site in United States.
Trial summary
The purpose of this trial is to compare two different rates of fluid administration during diabetic ketoacidosis (DKA) treatment in children to determine which fluid administration rate is more beneficial for brain metabolism and for preventing or decreasing brain swelling during DKA. Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Diabetic Ketoacidosis
- What is being tested?
- intravenous fluid treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Jun 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- age 8-18 years
- diagnosis of diabetic ketoacidosis
- able to cooperate with MR scanning
Who cannot join
- pre-existing cerebral injury or brain structural abnormality
- dental hardware or other metal devices which would interfere with MR imaging
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Davis Medical Center, 2315 Stockton Blvd
Sacramento, California, 95817
About this study
The purpose of this trial is to compare two different rates of fluid administration during diabetic ketoacidosis (DKA) treatment in children to determine which fluid administration rate is more beneficial for brain metabolism and for preventing or decreasing brain swelling during DKA.
Read the detailed description
Cerebral edema (swelling of the brain) is the most frequent serious complication of diabetic ketoacidosis (DKA) in children. The cause of cerebral edema during DKA is not well understood. Recent studies suggest that it may result from lack of adequate blood flow to the brain during DKA, before treatment starts. Brain injury, resulting in edema, may occur before treatment because of lack of adequate blood flow to the brain and additional injury may occur when adequate blood flow is re-established during treatment (called reperfusion injury). Because additional injury may occur during treatment, it is important to understand whether the rate of administration of intravenous fluids, and, therefore, the speed of reperfusion of the brain, is related to the degree of brain swelling and injury. Most current treatment protocols indicate that intravenous fluids should be administered slowly, but it may be possible that brain injury and swelling might be lessened if adequate blood flow is established more quickly.
In this study, researchers will use magnetic resonance (MR) imaging to compare two different rates of fluid administration during DKA treatment in children. The investigators will use MR imaging to measure brain swelling and metabolism at three time points-twice during treatment and once after recovery from DKA-and will compare these measurements to determine which fluid administration rate has more beneficial effects on brain metabolism and brain swelling.
The study's researchers hypothesize that more rapid re-establishment of blood flow to the brain (via more rapid administration of intravenous fluids) will result in less brain swelling and injury than slower rehydration with delayed re-establishment of adequate brain blood flow will.
- Conditions
- Diabetic Ketoacidosis
- Being tested
- intravenous fluid treatment
- Keywords
- diabetic ketoacidosis, DKA, cerebral edema, brain edema
- Medical subject headings
- Diabetic Ketoacidosis, Brain Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intravenous fluid treatmentOther
infusion of intravenous fluids (0.9% saline and 0.45% saline)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Slower infusion rate: Patients in this arm will receive an initial intravenous fluid bolus of 10cc/Kg followed by rehydration calculated to replace a deficit of 7.5% of body weight over 48 hours. Receives: Other: intravenous fluid treatment |
| 2 | Active comparator | More rapid infusion: Patients in this arm will receive an initial bolus of 20 cc/Kg of intravenous fluids followed by replacement of an estimated deficit of 10% of body weight over 36 hours plus replacement of 1/2 of urine output volume. Receives: Other: intravenous fluid treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient)
In both groups, brain Apparent Diffusion Coefficient (ADC) measures at 3-6 hours and 9-12 hours after beginning DKA treatment were averaged to determine overall brain ADC during DKA treatment. The brain ADC indicates the distribution of water in the brain and is an indicator of brain swelling (edema). The overall brain ADC values during DKA treatment were compared with the brain ADC measured after recovery to assess the degree of brain edema formation during DKA treatment. The difference in brain ADC, calculated as the averaged treatment values minus the recovery value, was used as the main outcome measure to indicate the degree of brain edema formation
Measured: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
Secondary outcomes (1)
Brain NAA/Creatine Ratio & Brain Lactate Measured by MR Spectroscopy, Cerebral Blood Flow & Oxygen Saturation Measured by MR Perfusion Weighted Imaging & Near Infrared Spectroscopy, Mental Status Evaluated by Glasgow Coma Scale Scores.
Measured: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2008 (estimated)
- Study startJun 2008
- Primary completionMar 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetic KetoacidosisStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicole Glaser, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00629707
- Sponsor's protocol ID
- R01NS048610
- Other IDs
- R01NS052619-01, R01NS052592-01
- Status last verified
- Sep 2012
- First submitted
- 4 Mar 2008
- Last updated
- 18 Sep 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Trainor JL, Glaser NS, Tzimenatos L, Stoner MJ, Brown KM, McManemy JK, Schunk JE, Quayle KS, Nigrovic LE, Rewers A, Myers SR, Bennett JE, Kwok MY, Olsen CS, Casper TC, Ghetti S, Kuppermann N; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group. Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis. Ann Emerg Med. 2023 Aug;82(2):167-178. doi: 10.1016/j.annemergmed.2023.01.001. Epub 2023 Apr 5.
PubMed 37024382Rewers A, Kuppermann N, Stoner MJ, Garro A, Bennett JE, Quayle KS, Schunk JE, Myers SR, McManemy JK, Nigrovic LE, Trainor JL, Tzimenatos L, Kwok MY, Brown KM, Olsen CS, Casper TC, Ghetti S, Glaser NS; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group. Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis. Diabetes Care. 2021 Sep;44(9):2061-2068. doi: 10.2337/dc20-3113. Epub 2021 Jun 29.
PubMed 34187840Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816.
PubMed 29897851
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral Edema in Pediatric Diabetic Ketoacidosis
- ClinicalTrials.gov ID
- NCT00629707
- Acronym / sponsor ID
- R01NS048610
- Conditions
- Diabetic Ketoacidosis
- Keywords
- diabetic ketoacidosis, DKA, cerebral edema, brain edema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jun 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 6 Mar 2008 (estimated)
- Results
- Posted 12 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to compare two different rates of fluid administration during diabetic ketoacidosis (DKA) treatment in children to determine which fluid administration rate is more beneficial for brain metabolism and for preventing or decreasing brain swelling during DKA.
Detailed description
Cerebral edema (swelling of the brain) is the most frequent serious complication of diabetic ketoacidosis (DKA) in children. The cause of cerebral edema during DKA is not well understood. Recent studies suggest that it may result from lack of adequate blood flow to the brain during DKA, before treatment starts. Brain injury, resulting in edema, may occur before treatment because of lack of adequate blood flow to the brain and additional injury may occur when adequate blood flow is re-established during treatment (called reperfusion injury). Because additional injury may occur during treatment, it is important to understand whether the rate of administration of intravenous fluids, and, therefore, the speed of reperfusion of the brain, is related to the degree of brain swelling and injury. Most current treatment protocols indicate that intravenous fluids should be administered slowly, but it may be possible that brain injury and swelling might be lessened if adequate blood flow is established more quickly.
In this study, researchers will use magnetic resonance (MR) imaging to compare two different rates of fluid administration during DKA treatment in children. The investigators will use MR imaging to measure brain swelling and metabolism at three time points-twice during treatment and once after recovery from DKA-and will compare these measurements to determine which fluid administration rate has more beneficial effects on brain metabolism and brain swelling.
The study's researchers hypothesize that more rapid re-establishment of blood flow to the brain (via more rapid administration of intravenous fluids) will result in less brain swelling and injury than slower rehydration with delayed re-establishment of adequate brain blood flow will.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Other: intravenous fluid treatmentSlower infusion rate: Patients in this arm will receive an initial intravenous fluid bolus of 10cc/Kg followed by rehydration calculated to replace a deficit of 7.5% of body weight over 48 hours. |
| 2 | Active comparator | Other: intravenous fluid treatmentMore rapid infusion: Patients in this arm will receive an initial bolus of 20 cc/Kg of intravenous fluids followed by replacement of an estimated deficit of 10% of body weight over 36 hours plus replacement of 1/2 of urine output volume. |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- age 8-18 years
- diagnosis of diabetic ketoacidosis
- able to cooperate with MR scanning
Key exclusion criteria (2 listed)
- pre-existing cerebral injury or brain structural abnormality
- dental hardware or other metal devices which would interfere with MR imaging
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 |
|---|---|---|
| intravenous fluid treatmentinfusion of intravenous fluids (0.9% saline and 0.45% saline) | Other | 1, 2 |
Primary outcome
Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient)
Time frame: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
In both groups, brain Apparent Diffusion Coefficient (ADC) measures at 3-6 hours and 9-12 hours after beginning DKA treatment were averaged to determine overall brain ADC during DKA treatment. The brain ADC indicates the distribution of water in the brain and is an indicator of brain swelling (edema). The overall brain ADC values during DKA treatment were compared with the brain ADC measured after recovery to assess the degree of brain edema formation during DKA treatment. The difference in brain ADC, calculated as the averaged treatment values minus the recovery value, was used as the main outcome measure to indicate the degree of brain edema formation
1 secondary outcome
Brain NAA/Creatine Ratio & Brain Lactate Measured by MR Spectroscopy, Cerebral Blood Flow & Oxygen Saturation Measured by MR Perfusion Weighted Imaging & Near Infrared Spectroscopy, Mental Status Evaluated by Glasgow Coma Scale Scores.
Time frame: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37024382Trainor JL, Glaser NS, Tzimenatos L, Stoner MJ, Brown KM, McManemy JK, Schunk JE, Quayle KS, Nigrovic LE, Rewers A, Myers SR, Bennett JE, Kwok MY, Olsen CS, Casper TC, Ghetti S, Kuppermann N; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group. Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis. Ann Emerg Med. 2023 Aug;82(2):167-178. doi: 10.1016/j.annemergmed.2023.01.001. Epub 2023 Apr 5.
- Derived from this study: PubMed 34187840Rewers A, Kuppermann N, Stoner MJ, Garro A, Bennett JE, Quayle KS, Schunk JE, Myers SR, McManemy JK, Nigrovic LE, Trainor JL, Tzimenatos L, Kwok MY, Brown KM, Olsen CS, Casper TC, Ghetti S, Glaser NS; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group. Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis. Diabetes Care. 2021 Sep;44(9):2061-2068. doi: 10.2337/dc20-3113. Epub 2021 Jun 29.
- Derived from this study: PubMed 29897851Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816.
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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.
Nicole Glaser, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intravenous fluid treatment in people with Diabetic Ketoacidosis, run by University of California, Davis at 1 site 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 3 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 18 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cerebral Edema Measured by MR Imaging (Apparent Diffusion Coefficient) (time frame: twice during DKA treatment, once at 3-6 hours and at 9-12 after treatment. A normal comparison measurement will be done after recovery from DKA, at least 72 hours after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00629707, which also lists 3 linked publications.
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 18 Sep 2012.