Thiamine and Acute Decompensated Heart Failure: Pilot Study

Targeting Myocardial Energy Metabolism for the Treatment of Acute Heart Failure: The Effect of Thiamine on Biochemical, Electrocardiographic and Respiratory Parameters in Hospitalized Patients.

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Diabetes
• Intervention / Treatment: Drug: Thiamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Drug: Placebo; D5W (50 ml)
Experimental: Thiamine; Receives thiamine	Drug: Thiamine; Thiamine (100 mg) in 50 ml D5W, x 2.; Other Names: Vitamin B1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	8-Hour

Collaborators and Investigators

• Sponsor: Baystate Medical Center
• Collaborators: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Howard Smithline, MD, Baystate Medical Center

Publications and helpful links

General Publications

• Smithline HA, Donnino M, Blank FSJ, Barus R, Coute RA, Knee AB, Visintainer P. Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial. BMC Complement Altern Med. 2019 May 6;19(1):96. doi: 10.1186/s12906-019-2506-8.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 16, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (Estimate): May 20, 2008

Study Record Updates

• Last Update Posted (Estimate): August 21, 2013
• Last Update Submitted That Met QC Criteria: August 12, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 07-059