Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis
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|ClinicalTrials.gov Identifier: NCT03717896|
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : January 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Diabetic Ketoacidosis||Drug: 200mg IV thiamine in 50mL 0.9% saline Drug: Placebo||Phase 2|
Thiamine (vitamin B1) is a water-soluble vitamin that plays a key role in aerobic glucose metabolism. Thiamine is a cofactor of pyruvate dehydrogenase (PDH), an enzyme that must be activated for entry into the Krebs Cycle for aerobic metabolism. PDH activity is reduced in thiamine deficient states, resulting in a shift in pyruvate metabolism to the anaerobic pathway. This leads to increased lactate production and acidosis. Thiamine loss in the urine, with consequent thiamine deficiency, is not uncommon in diabetes. The investigators' preliminary studies have found that thiamine deficiency in occurs in as many as 39% of patients with DKA, and that thiamine levels are inversely associated with lactate and acidosis. The investigator hypothesizes that treating DKA patients with intravenous thiamine will lead to faster resolution of acidosis and improved aerobic metabolism. The investigator's secondary hypothesis is that thiamine treatment will shorten stays in the ICU and hospital and lead to utilization of fewer hospital resources.
In this randomized, double-blind, placebo-controlled trial, patients admitted to the hospital with DKA who are enrolled in the study will be randomized to either intravenous thiamine (200mg in 0.9% saline) twice daily for two days or an identical volume of 0.9% saline on the same schedule. The investigator's primary outcome is change in bicarbonate over the 24 hours following enrollment, with measurements at 0, 6, 12, 18, 24 hours, using a linear mixed-effects model. Secondarily, patients will be stratified by Type I and Type II DM. Additionally, a pre-planned sub-analysis of thiamine deficient subjects will be performed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis|
|Actual Study Start Date :||November 21, 2018|
|Estimated Primary Completion Date :||April 21, 2023|
|Estimated Study Completion Date :||October 1, 2023|
200mg IV thiamine in 50mL 0.9% saline twice daily for 2 days
Drug: 200mg IV thiamine in 50mL 0.9% saline
Thiamine 200mg IV every 12 hours for 2 days
Other Name: Vitamin B1
Placebo Comparator: Placebo
100mL 0.9% saline twice daily for two days
50mL 0.9% saline
- plasma bicarbonate levels [ Time Frame: 24 hours ]Our primary outcome is change in bicarbonate over the 24 hours following enrollment with measurements at 0, 6, 12, 18, 24 hours using a linear-effects model
- anion gap [ Time Frame: 24 hours ]Our secondary outcomes include change in anion gap over the 24 hours following enrollment with measurements at 0, 6, 12, 18, 24 hours using a linear-effects model
- lactate [ Time Frame: 24 hours ]Another secondary outcome is change in lactate over the 24 hours following enrollment with measurements at 0, 6, 12, 18, 24 hours using a linear-effects model
- oxygen consumption by circulating mononuclear cells [ Time Frame: 24 hours ]Oxygen consumption by circulating mononuclear cells is an index of whole body oxidative glucose metabolism. It also reflects whole body thiamine status due to the critical cofactor role of thiamine in oxidative metabolism. Mononuclear cell oxygen consumption will be assessed by the investigators when the patient is admitted into the study and again after 24 hours to determine if there is a difference between the two groups.
- ICU length of stay [ Time Frame: 24 hours ]ICU length of stay reflects how rapidly the patient recovers from the most severe consequences of diabetic ketoacidosis. The investigators will record this parameter from hospital records.to determine if there is a difference between the two groups.
- hospital length of stay [ Time Frame: 24 hours ]Hospital length of stay reflects how long it takes a diabetic ketoacidosis patient to recover to the point where he/she can be released from the hospital. The investigators will record this parameter from hospital records to determine if there is a difference between the two groups.
- hospital resource usage [ Time Frame: 24 hours ]The investigators will record this parameter from hospital records to determine if there is a difference between the two groups
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717896
|Contact: Michael W Donnino, MD||(617) firstname.lastname@example.org|
|Contact: Francesca Montillo, MSemail@example.com|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Michael W Donnino, MD firstname.lastname@example.org|
|Contact: Jacob Boise 617-754-2881 email@example.com|
|Principal Investigator: Michael W Donnino, MD|
|Sub-Investigator: Chris Hansen, MD|