Thiamine and Acute Decompensated Heart Failure: Pilot Study

• Sponsor: Baystate Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00680706
• Collaborator: Beth Israel Deaconess Medical Center (Other)
• Enrollment: 131
• Locations: 2
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 65.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Diabetes	Drug: Thiamine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Targeting Myocardial Energy Metabolism for the Treatment of Acute Heart Failure: The Effect of Thiamine on Biochemical, Electrocardiographic and Respiratory Parameters in Hospitalized Patients.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. Effect of Thiamine Supplementation on Dyspnea [8-Hour]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

1. Taking a daily thiamine supplementation (any multivitamin or specific thiamine supplementation within the past 2 weeks. Fortified foods, such as cereals, are acceptable

2. Taking a daily fatty acid supplement.

3. Pregnancy as determined by standard serum or urine b-HCG assay.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
2	Baystate Medical Center	Springfield	Massachusetts	United States	01199

Sponsors and Collaborators

• Baystate Medical Center
• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Howard Smithline, MD, Baystate Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Howard Smithline, Chief, Emergency Medicine Research, Baystate Medical Center
• ClinicalTrials.gov Identifier: NCT00680706
• Other Study ID Numbers: 07-059
• First Posted: May 20, 2008
• Last Update Posted: Aug 21, 2013
• Last Verified: Aug 1, 2013

• Additional relevant MeSH terms: Heart Failure; Thiamine

Study Results

Participant Flow

Recruitment Details	Recruitment: January 2008 to February 2010 Location: Emergency Department
Pre-assignment Detail	One subject was dropped by the PI after consent but before randomization because the subject did not meet the inclusion/exclusion criteria.

Arm/Group Title	Thiamine	Control
Arm/Group Description	Receives thiamine, 100 mg intravenously at baseline (time 0-hour) and again at time 24-hour.	Receives placebo
Period Title: Overall Study
STARTED	70	60
COMPLETED	63	55
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Thiamine	Control	Total
Arm/Group Description	Receives thiamine	Receives placebo	Total of all reporting groups
Overall Participants	70	60	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (13)	73 (13)	73 (13)
Sex/Gender, Customized (participants) [Number]
Male	34 48.6%	33 55%	67 51.5%
Female	33 47.1%	27 45%	60 46.2%
Unknown	3 4.3%	0 0%	3 2.3%

Outcome Measures

1. Primary Outcome

Title	Effect of Thiamine Supplementation on Dyspnea
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Thiamine
Arm/Group Description	Placebo
Measure Participants	55	63
Mean (95% Confidence Interval) [mm]	34	32

2. Primary Outcome

Title	Effect of Thiamine Supplementation on Dyspnea
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Thiamine
Arm/Group Description	Placebo
Measure Participants	55	63
Mean (95% Confidence Interval) [mm]	19	28

Adverse Events

Arm/Group Title	Thiamine		Control
Arm/Group Description	Receives thiamine		Receives placebo
All Cause Mortality
	Thiamine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Thiamine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Thiamine		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/55 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.