Diabetes, Heart Failure
Conditions
Brief summary
Heart failure remains an increasing cause of morbidity and mortality in the United States even in the face of recent advances in the treatment of cardiovascular disease. There is an urgent need to reevaluate the treatment of heart failure. Shifting substrate utilization used in energy metabolism from fatty acids to glucose is beneficial to the heart presumably by increasing the efficiency of ATP production. Several new drugs for the treatment of cardiac ischemia work by this mechanism. There is increasing evidence that patients with heart failure may also benefit by the same type of intervention. Patients with heart failure are known to have low serum thiamine levels because of poor dietary intake and increased urinary excretion. Inadequate thiamine will deleteriously shift substrate utilization from glucose to fatty acids. We hypothesize that thiamine supplementation will be beneficial for patients with heart failure by increasing glucose and decreasing fatty acid utilization. This will be initially tested in a pilot double-blinded placebo controlled study of thiamine supplementation in diabetic and non-diabetic patients presenting to the emergency department with acute decompensated heart failure.
Interventions
DRUGThiamine
Thiamine (100 mg) in 50 ml D5W, x 2.
DRUGPlacebo
D5W (50 ml)
Sponsors
Beth Israel Deaconess Medical Center
Baystate Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. History of heart failure on a loop diuretic. 2. Worsening dyspnea over the past 24 hours. 3. Currently dyspneic sitting or supine, on or off oxygen. 4. Radiographic cephalization of vessels. This criteria is not needed if the patient has no other reason for being dyspneic after being evaluated in the emergency department. 5. Elevated NT pro-BNP (\>450). 6. Able to communicate in English or Spanish. 7. Able and willing to provide informed consent. 8. Age \> 18 years. 9. A primary admitting diagnosis of acute decompensated heart failure.
Exclusion criteria
1. Renal failure on dialysis. 2. Severe valvular disease. 3. EKG criteria for acute myocardial infarction (ST segment elevation \> 1mm on two contiguous leads). 4. Initial troponin elevated. 5. Ventricular arrhythmia (ventricular tachycardia or fibrillation). 6. Supraventricular arrhythmia (atrial fibrillation / flutter) with a ventricular rate \>120 beats per minute. 7. Taking a daily thiamine supplementation (any multivitamin or specific thiamine supplementation within the past 2 weeks. Fortified foods, such as cereals, are acceptable 8. Taking a daily fatty acid supplement. 9. Pregnancy as determined by standard serum or urine b-HCG assay.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Thiamine Supplementation on Dyspnea | Baseline | Sitting Upright on Oxygen. Measured using a 10-centimeter visual analog scale (VAS). Measures are in units of millimeters (mm). A smaller number should be interpreted as a less dyspnea. A larger number should be interpreted as a more dyspnea. Less dyspnea is a better clinical outcome than more dyspnea. |
Countries
United States
Participant flow
Recruitment details
Recruitment: January 2008 to February 2010 Location: Emergency Department
Pre-assignment details
One subject was dropped by the PI after consent but before randomization because the subject did not meet the inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Thiamine Receives thiamine | 70 |
| Control Receives placebo | 60 |
| Total | 130 |
Baseline characteristics
| Characteristic | Thiamine | Control | Total |
|---|---|---|---|
| Age Continuous | 73 years STANDARD_DEVIATION 13 | 73 years STANDARD_DEVIATION 13 | 73 years STANDARD_DEVIATION 13 |
| Sex/Gender, Customized Female | 33 participants | 27 participants | 60 participants |
| Sex/Gender, Customized Male | 34 participants | 33 participants | 67 participants |
| Sex/Gender, Customized Unknown | 3 participants | 0 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 63 | 0 / 55 |
| serious Total, serious adverse events | 0 / 63 | 0 / 55 |
Outcome results
Primary
Effect of Thiamine Supplementation on Dyspnea
Sitting Upright on Oxygen. Measured using a 10-centimeter visual analog scale (VAS). Measures are in units of millimeters (mm). A smaller number should be interpreted as a less dyspnea. A larger number should be interpreted as a more dyspnea. Less dyspnea is a better clinical outcome than more dyspnea.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Effect of Thiamine Supplementation on Dyspnea | 34 mm |
| Thiamine | Effect of Thiamine Supplementation on Dyspnea | 32 mm |
Primary
Effect of Thiamine Supplementation on Dyspnea
Sitting Upright on Oxygen. Measured using a 10-centimeter visual analog scale (VAS). Measures are in units of millimeters (mm). A smaller number should be interpreted as a less dyspnea. A larger number should be interpreted as a more dyspnea. Less dyspnea is a better clinical outcome than more dyspnea.
Time frame: 8-Hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Effect of Thiamine Supplementation on Dyspnea | 19 mm |
| Thiamine | Effect of Thiamine Supplementation on Dyspnea | 28 mm |