Thiamine As Adjunctive Therapy for Diabetic Ketoacidosis

Beth Israel Lahey Health

Status and phase: Completed; Phase 2

Conditions: Diabetic Ketoacidosis

Treatments: Drug: Placebo; Drug: 200mg IV thiamine in 50mL 0.9% saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03717896

1R01DK112886-01A1 (U.S. NIH Grant/Contract)

2018P000475

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled trial to determine if administration of intravenous thiamine will lead to quicker resolution of acidosis in patients admitted to the hospital with diabetic ketoacidosis. The investigators will secondarily investigate whether thiamine improves cellular oxygen consumption, shortens intensive care unit (ICU) and hospital stay or decreases hospital resource utilization.

Full description

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.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Bicarbonate ≤15 mEq/L
• Anion gap > 12 mEq/L
• Blood pH≤ 7.24 (if already obtained by clinical team)
• Urine ketones (qualitative) or serum ketones (β-hydroxybutyric acid) > 3 mmol/L
• Enrollment within 6 hours of presentation

Exclusion criteria

• Current thiamine supplementation ≥ 6 milligrams per day (i.e., more than a multivitamin)
• Competing causes of severe acidosis including seizure, carbon monoxide poisoning, cyanide toxicity, cardiac arrest, liver dysfunction (specifically defined as known cirrhosis)
• Known allergy to thiamine
• Competing indication for thiamine administration as judged by the clinical team (e.g., significant alcohol use)
• Research-protected populations (pregnant women and prisoners)
• Patient enrolled previously in same study
• Code status of Do Not Resuscitate/Do Not Intubate (DNR/DNI) or Comfort Measures Only (CMO)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

100 participants in 2 patient groups, including a placebo group

Thiamine

Experimental group

Description:

200mg IV thiamine in 50mL 0.9% saline twice daily for 2 days

Treatment:

Drug: 200mg IV thiamine in 50mL 0.9% saline

Placebo

Placebo Comparator group

Description:

100mL 0.9% saline twice daily for two days

Treatment:

Drug: Placebo