The Prevalence of Thiamin Deficiency in Ambulatory Patients With Heart Failure

This study has been completed.
Sponsor:
Collaborator:
Canadian Foundation for Dietetic Research (CFDR)
Information provided by (Responsible Party):
mary keith, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT00953823
First received: August 4, 2009
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

Patients with heart failure are at an increased risk for thiamin deficiency (TD), for many reasons such as malnutrition and the use of diuretic drugs. Thiamin is a B vitamin that plays an important role in the production of energy in body. Therefore, low levels of thiamin may limit the amount of energy available for the heart to pump blood. Recent thiamin supplementation trials have demonstrated significant improvements in heart function. However, while clinically important, the results of these studies are limited by their small sample sizes, indirect measurement of thiamin status and reliance on hospitalized patients. Therefore, the investigators' goal is to determine the prevalence of thiamin deficiency in ambulatory patients with heart failure by direct measurement of thiamin in red blood cells.


Condition
Heart Failure

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: The Prevalence of Thiamin Deficiency in Ambulatory Patients With Heart Failure

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • Prevalence of Thiamin deficiency as determined by Erythrocyte thiamin pyrophosphate (TPP) measured using a direct HPLC technique [ Time Frame: baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Eligible patients will be randomized to one of three commercially available doses of oral thiamin hydrochloride; 50 mg QD, 50 mg BID and 100 mg BID. They will take the supplements for 2 weeks. [ Time Frame: baseline to after two weeks of supplementation ] [ Designated as safety issue: No ]
  • Plasma samples will be analyzed for the plasma levels of NE, BNP, F2-isoprostanes [ Time Frame: baseline and after supplementation ] [ Designated as safety issue: No ]
  • Urinary excretion of thiamin following the 2 week supplementation period. [ Time Frame: by the end of two-week supplementation period ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood test


Enrollment: 110
Study Start Date: May 2009
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Detailed Description:

Thiamin is a water-soluble B-complex vitamin which is supplied primarily from cereals and enriched grains in the ordinary diet. The majority of absorbed thiamin combines with ATP in the body to form thiamin pyrophosphate (TPP). TPP is a coenzyme which is involved in a number of energy production reactions in the body (metabolism of carbohydrates and some amino acids) . Therefore, theoretically, TD reduces the release of metabolic energy in the tissues . The adverse effects of TD include biventricular myocardial failure, tachycardia, peripheral edema, and retention of sodium which occurs as a result of heart failure . Therefore, our assumption is that TD in CHF patients may result in depletion of cellular energy and subsequently impair cardiac function. Previous studies done on CHF patients with TD found that thiamin supplementation was associated with improvement in heart contractility.

Patients with heart failure are at an increased risk for TD, for many reasons such as malnutrition, anorexia and the use of diuretic drugs, such as furosemide. Several studies have demonstrated a high prevalence of TD in hospitalized patients with heart failure, ranging from 13 % to 91% depending on the population studied. This wide variation is due to differences in the underlying nutrition status of subjects, the concurrent use of medications including loop diuretics, the severity of disease, and the measurement technique used for the assessment of thiamin status. These studies however, while clinically important, are limited by their small sample size and indirect measurement of thiamin status. Also, these studies have focused exclusively on the hospitalized patients, whereas ambulatory HF patients have received little attention.

Therefore, our primary objective to conduct a prospective, cross-sectional study to investigate the prevalence of thiamin deficiency in a large group of ambulatory patients with heart failure using High-Performance Liquid Chromatography (HPLC). This method has many advantages including its high level of recovery (102% on average), high intra- and inter-day precisions within 5-9%, as well as having a considerably low elution time of 15 min.

Our secondary objective is to conduct a trial using oral thiamin supplements alone in three practical doses in order to estimate the minimum dose of oral thiamin required to effectively replete tissue stores. We also hypothesize that oral thiamin supplementation will reduce neurohormonal stimulation (NE, BNP,as well as oxidative stress(F2-Isoprostanes).

Therefore,this study will provide critical data on the prevalence of TD in ambulatory patients with HF as well as defining what factors are predictive of TD in this population. Furthermore, this study will determine an effective dose of oral thiamin supplementation that will restore red blood cell thiamin levels. Determining an effective dose will not only justify our choice of thiamin supplementation in future studies but will guide clinicians in recommending thiamin supplementation to their patients with heart failure in the community.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Cardiology Clinic (St Michael's Hospital)

Criteria

Inclusion Criteria:

  • Patients with the primary diagnosis of ischemic, dilated, idiopathic or valvular HF characterized by an ejection fraction of < 45% (echocardiography or radionuclide scan)
  • Patients with NYHA class I-IV symptoms

Exclusion Criteria:

  • Patients who are unable or unwilling to provide informed consent
  • Patients with any concurrent condition which would result in TD, namely, gastrointestinal disorders (Crohn's disease, ulcerative colitis), liver disease, prolonged diarrhoeal disease, dialysis, prolonged fever, infection or renal failure
  • Patients who are rapidly deteriorating, who are not on a stable medication regimen (≥ 2 months) or have been hospitalized for acute decompensated HF in the last 2 months
  • Patients who are on experimental medications
  • Patients who consume excessive alcohol (> 3 drinks per day), have a documented history of alcoholism or have documented alcoholic cardiomyopathy
  • Patients who are pregnant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00953823

Locations
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
St. Michael's Hospital, Toronto
Canadian Foundation for Dietetic Research (CFDR)
Investigators
Principal Investigator: Mary Keith, PhD, RD St. Michael's Hospital, Toronto
Principal Investigator: Andrew Yan, MD Cardiologist, St. Michael's Hospital
Principal Investigator: Abdul Al-Hesayen, MD Cardiologist, St. Michael's Hospital
  More Information

No publications provided

Responsible Party: mary keith, Coordinator of Nutrition and Dietetic Education/Research, St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT00953823     History of Changes
Other Study ID Numbers: REB 09-031
Study First Received: August 4, 2009
Last Updated: December 21, 2012
Health Authority: Canada: Health Canada

Keywords provided by St. Michael's Hospital, Toronto:
Thiamin supplementation
Thiamin deficiency
Heart failure
Heart function
Vitamin B1 supplementation

Additional relevant MeSH terms:
Heart Failure
Thiamine Deficiency
Beriberi
Heart Diseases
Cardiovascular Diseases
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Thiamine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014