Supplementation of Glutamine and Fish Oil Versus Placebo in Patients With Heart Failure (GLUTFISH-HF)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: Glutamine and Fish Oil Supplementation

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

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: Placebo; The placebo for fish oil will be safflower oil. For glutamine, soy powder will serve as the placebo.	Drug: Placebo; 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.
Active Comparator: Glutamine/Fishoil; 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; 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.

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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Paolo C. Colombo, MD, Columbia University

Publications and helpful links

General Publications

• Shahzad K, Chokshi A, Schulze PC. Supplementation of glutamine and omega-3 polyunsaturated fatty acids as a novel therapeutic intervention targeting metabolic dysfunction and exercise intolerance in patients with heart failure. Curr Clin Pharmacol. 2011 Nov;6(4):288-94. doi: 10.2174/157488411798375958.
• Wu C, Kato TS, Ji R, Zizola C, Brunjes DL, Deng Y, Akashi H, Armstrong HF, Kennel PJ, Thomas T, Forman DE, Hall J, Chokshi A, Bartels MN, Mancini D, Seres D, Schulze PC. Supplementation of l-Alanyl-l-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure. Circ Heart Fail. 2015 Nov;8(6):1077-87. doi: 10.1161/CIRCHEARTFAILURE.115.002073. Epub 2015 Aug 12.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 14, 2012
• First Submitted That Met QC Criteria: February 16, 2012
• First Posted (Estimate): February 17, 2012

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Heart Failure; Inflammation; Fish oil; Glutamine; Metabolism; Muscle Function; Skeletal Muscle Function
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: AAAE8356