Supplementation of Glutamine and Fish Oil Versus Placebo in Patients With Heart Failure

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to determine whether supplementation of glutamine and fish oil can improve peripheral skeletal muscle function and metabolism in patients with heart failure. The investigators propose a randomized, double-blind, placebo controlled study comparing the combined supplementation of fish oil and glutamine with placebo in patients with stable heart failure. 30 patients with heart failure will be randomized to either receiving 6.5 g fish oil/d and 8 g glutamine/d (n=15) or placebo (n=15) for 90 days. The primary outcome in this study is the change in muscle functional capacity measured as changes in maximum muscle strength and fatigability, peak VO2 and exercise time after supplementation. A secondary outcome is the measurement of systemic and local markers of inflammation.

Official Title
-----------------
Effects of Glutamine and Fish Oil on Muscle Function in Heart Failure (GlutFish-HF)

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Drug: Glutamine and Fish Oil Supplementation
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age greater than 18 years, left ventricular ejection fraction less than or equal to 35%, stable on standard HF medications, and optimal medical therapy. Exclusion Criteria: major cardiovascular events, procedures in the last 6 months, dementia, presence of cardiovascular diseases that may lead to harm if the patient took part in the study (congenital heart disease, long QT syndrome, hypertrophic cardiomyopathy, active myocarditis).

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The placebo for fish oil will be safflower oil. For glutamine, soy powder will serve as the placebo. | Drug: Placebo<br>* This is a prospective, randomized double-blind, placebo-controlled study design. 38 subjects will be randomized to two groups (19 patients in each group), one taking active fish oil and glutamine supplementation and the other taking placebo for 90 days.<br>|
| Active Comparator: Glutamine/Fishoil<br>3.285 g of EPA and 3.285 g of Docosahexaenoic acid (DHA) and L-alanyl-glutamine (8g/d). | Drug: Glutamine and Fish Oil Supplementation<br>* This is a prospective, randomized double-blind, placebo-controlled study design. 38 subjects will be randomized to two groups (19 patients in each group), one taking active fish oil and glutamine supplementation and the other taking placebo for 90 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Skeletal Muscle Function Capacity- Isometric Contractions (PKTQ/BW) | For isometric contractions, participants contracted against a constant 60-degree angle at the knee (dominant leg) and a constant 30 degree angle at the elbow (dominant arm) for 6 seconds. Participants alternated between flexion and extension, 3 repetitions each with a 30 second rest period between each. Data was collected to determine peak torque to body weight (peak torque (PKTQ)/ body weight (BW)). | Baseline | 
| 90 Day Skeletal Muscle Function Capacity- Isometric Contractions (PKTQ/BW) | For isometric contractions, participants contracted against a constant 60-degree angle at the knee (dominant leg) and a constant 30 degree angle at the elbow (dominant arm) for 6 seconds. Participants alternated between flexion and extension, 3 repetitions each with a 30 second rest period between each. Data was collected to determine peak torque to body weight (peak torque (PKTQ)/ body weight (BW)). | 90 Days | 
| Baseline Muscle Function Capacity- Isokinetic Contractions (PKTQ/BW) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | Baseline | 
| 90 Day Muscle Function Capacity- Isokinetic Contractions (PKTQ/BW) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | 90 Days | 
| Baseline Muscle Function Capacity- Isokinetic Contractions (Work (WK)/Body Weight (BW)) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | Baseline | 
| 90 Days Muscle Function Capacity- Isokinetic Contractions (Work (WK)/Body Weight (BW)) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | 90 Days | 
| Baseline Muscle Function Capacity- Isokinetic Contractions (Total Work) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | Baseline | 
| 90 Day Muscle Function Capacity- Isokinetic Contractions (Total Work) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | 90 Days | 
| Baseline Muscle Function Capacity- Isokinetic Contractions (Average Power) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | Baseline | 
| 90 Day Muscle Function Capacity- Isokinetic Contractions (Average Power) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | 90 Days | 
| Baseline Muscle Function Capacity- Isokinetic Contractions (Time to Peak Torque) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | Baseline | 
| 90 Day Muscle Function Capacity- Isokinetic Contractions (Time to Peak Torque) | For isokinetic contractions, subjects performed flexion and extension movements at the knee and elbow for 5 repetitions at a speed of 60 degrees/second. This was followed by a rest period of 2.5 minutes. For the second isokinetic protocol, subjects performed 25 repetitions of flexion and extension movements at the knee and elbow at a speed of 180 degrees/second. | 90 Days | 
| Percent Change in Peak Effort Oxygen Consumption | Peak effort oxygen consumption (VO2 max) is measured using Cardiopulmonary Exercise Testing (CPET). | Baseline to 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Systemic and Local Inflammation | Systemic and local marker of inflammation as measured by tumor necrosis factor-alpha, units pg/mL | Baseline | 
| 90 Day Systemic and Local Inflammation | Systemic and local marker of inflammation as measured by tumor necrosis factor-alpha, units pg/mL | 90 Days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart Failure, Skeletal Muscle Function, Metabolism, Inflammation, Glutamine, Fish oil, Muscle Function