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Effect of EPA and HMB on Strength in ICU Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Kentucky
Sponsor:
Information provided by (Responsible Party):
Gerald Supinski, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01270516
First received: January 4, 2011
Last updated: August 29, 2014
Last verified: August 2014

January 4, 2011
August 29, 2014
January 2014
October 2015   (final data collection date for primary outcome measure)
Improvement of skeletal muscle strength for one of the drugs compared to placebo [ Time Frame: By the second strength measurement (11 days) ] [ Designated as safety issue: No ]
The primary outcome to be assessed is whether skeletal muscle strength (diaphragm and limb) is higher at the end of the administration trial (i.e. at 11 days) for patients given one or both of the active drugs (EPA or HMB) as compared to strength measurements at 11 days for patients given the placebo.
Improvement of skeletal muscle strength for one of the drugs compared to placebo [ Time Frame: By the second strength measurement (7 days) ] [ Designated as safety issue: No ]
The primary outcome to be assessed is whether skeletal muscle strength (diaphragm and limb) is higher at the end of the administration trial (i.e. at 7 days) for patients given one of the active drugs (EPA or HMB) as compared to strength measurements at 7 days for patients given the placebo.
Complete list of historical versions of study NCT01270516 on ClinicalTrials.gov Archive Site
duration of mechanical ventilation [ Time Frame: weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Effect of EPA and HMB on Strength in ICU Patients
Effect of EPA and HMB on Diaphragm and Limb Muscle Strength in Mechanically Ventilated Patients

The investigators will determine if administration of HMB (hydroxymethylbutyrate) or EPA (eicosapentaenoic acid) will increase diaphragm and limb muscle strength for patients on breathing machines in an intensive care unit. The investigators will first measure the strength of the diaphragm and a limb muscle (the quadriceps)using magnetic stimulators to activate these muscles. Muscle size will be measured by using an ultrasound to measure diaphragm thickness and quadriceps thickness. The investigators will also perform a vastus lateralis muscle biopsy. Patients will then be randomized to receive either placebo (saline 30 ml every 12 hours via the GI tract, EPA (1000 mg given every 12 hours via the GI tract), HMB (1500 mg given every 12 hours via the GI tract), or the combination of EPA (1000 mg given every 12 hours via the GI tract) and HMB (1500 mg given every 12 hours via the GI tract). Drugs will be given for 10 days; at the end of this time (on day 11), strength measurements, ultrasound muscle size measurements, and the vastus lateralis biopsy will be repeated. On day 21 an additional followup set of diaphragm and quadriceps strength and size measurements will be made (the biopsy will not be repeated for this last set of measurements). Patients will be followed clinically and patient outcomes (mortality, duration of mechanical ventilation after study entry) will be recorded.

Objectives. There is a single objective for this study, namely, to determine if early administration of either EPA or HMB can prevent or reverse the development of respiratory muscle weakness in critically ill, mechanically ventilated patients. The investigators plan to randomize patients accepted into this protocol to administration of either a control (saline enteral control solution), EPA administration (enteral EPA), HMB (enteral HMB), or a combination of EPA and HMB. Drugs will be administered for 10 days and measurements of diaphragm and quadriceps strength and size will be performed immediately before (day 0) and immediately after (day 11) the period of drug administration. A third set of measurements (diaphragm and quadriceps strength and size) will be performed on day 21. Vastus lateralis muscle biopsies will also be taken on days 0 and 11; no biopsy will be performed for day 21 assessments. The investigators will also perform a chart review and assess ventilator mechanics (respiratory system static compliance and inspiratory airway resistance) at the time of the initial strength assessment. Patient outcomes (time on mechanical ventilation and mortality) will also be recorded. The investigators would expect that mean diaphragm strength and limb muscle strength measurements will be similar for four groups immediately before initiation of drug administration. The hypothesis will be supported if, post drug administration, diaphragm and limb muscle strength are higher for patients receiving EPA and/or HMB than the control group receiving no active drug.

Study Design.

The basic study design is to:

  1. measure magnetic stimulated Pdi twitch and quadriceps strength and size, obtain a muscle biopsy from the vastus lateralis of the quadriceps, determine respiratory system compliance, determine airway resistance, and perform a chart review,
  2. randomize patients to treatment with either: control solutions (30 ml of enteral saline solution every 12 hours), EPA (30 ml of enteral solution containing 1000 mg of EPA every 12 hours), HMB (30 ml of enteral solution containing 1500 mg HMB every 12 hours) or both EPA (30 ml of enteral solution containing 1000 mg of EPA every 12 hours) and HMB (30 ml of enteral solution containing 1500 mg HMB every 12 hours).
  3. continue drugs for 10 days then
  4. on day 11 remeasure magnetic stimulated Pdi twitch and quadriceps strength, repeat measurements of diaphragm and quadriceps size (i.e. thickness), repeat the vastus lateralis muscle biopsy, determine respiratory system compliance, determine airway resistance, and perform a chart review.
  5. on day 21 remeasure magnetic stimulated Pdi twitch and quadriceps strength, and repeat measurements of diaphragm and quadriceps size (i.e. thickness), and perform another chart review.

For each chart review the investigators will obtain the following information: age, sex, diagnoses, reason for institution of mechanical ventilation, vital signs, bedside parameters of mechanical ventilation use (including mode of ventilation, duration of ventilation, level of oxygen, breath volume and rate, % triggered breaths), most recent arterial blood gas values, chest radiograph readings, recorded assessments of limb muscle strength and mental status.

Study Population. Adult patients requiring mechanical ventilation for more than 24 hours in one of the University of Kentucky adult ICU's will be asked to participate. Patients will be excluded if: (a) the physician caring for the patient determines that the patient is too unstable to tolerate these measurements, (b) if the patient requires high dose pressors (more than 15 mcg/min of norepinephrine or more than 15 mg/kg/min of dopamine), (c) if the patient requires more than 80% FiO2 or more than 15 cm H2O of PEEP, (d) if the patient has a cardiac pacemaker or implanted defibrillator, (e) if the patient has received neuromuscular blocking agents within the 48 hours preceding testing or has a known preexisting muscular disease, (f) if the patient has a recent history of variceal bleeding, and (g) if the patient is excessively sedated or mentally obtunded as judged by an inability to follow verbal commands. The investigators will also not study pregnant females, prisoners, or institutionalized decisionally impaired patients.

The goals are to recruit 80 patients into the study over a 24 month period (5 patients/month, 20 patients per experimental group). The investigators will study patients regardless of sex, race, or adult age. It is hoped that sufficient minorities and women will be studied so that the subject population is representative of the general patient population, but the investigators will be somewhat constrained by the numbers of available patients and the day to day makeup of the patient population in the UK ICU's. Inclusion of minorities and women will make the study results more generally applicable.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Muscle Weakness
  • Drug: HMB, hydroxymethylbutyrate
    Hydroxymethylbutyrate will be given as 1500 mg powder dissolved in 30 ml saline given enterally every 12 hours for 7 days
    Other Name: This agent is an over the counter biopharmaceutical
  • Drug: EPA, eicosapentaenoic acid
    EPA given as 1000 mg solution in saline (30 ml) administered enterally every 12 hours for 7 days
    Other Name: This is an over the counter biopharmaceutical
  • Placebo Comparator: Control, to be given saline solution
    Intervention: This group will be given saline (30 ml every 12 hours) for 10 days
  • Experimental: EPA, eicosapentaenoic acid
    This group will be given 1000 mg EPA every 12 hours for 10 days
    Intervention: Drug: EPA, eicosapentaenoic acid
  • Experimental: HMB, hydroxymethylbutyrate
    This arm will be given HMB (1500 mg) every 12 hours for 10 days.
    Intervention: Drug: HMB, hydroxymethylbutyrate
  • Experimental: EPA and HMB
    This group will be given EPA (1000 mg every 12 hours given via the GI tract) and HMB (1500 mg every 12 hours given via the GI tract) for 10 days.
    Interventions:
    • Drug: HMB, hydroxymethylbutyrate
    • Drug: EPA, eicosapentaenoic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
May 2016
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult patients requiring mechanical ventilation for more than 24 hours in one of the University of Kentucky adult ICU's

Exclusion Criteria:

  • The physician caring for the patient determines that the patient is too unstable to tolerate these measurements,
  • If the patient requires high dose pressors (more than 15 mcg/min of norepinephrine or more than 15 mg/kg/min of dopamine),
  • If the patient requires more than 80% FiO2 or more than 15 cm H2O of PEEP,
  • If the patient has a cardiac pacemaker or implanted defibrillator,
  • If the patient has received neuromuscular blocking agents within the 48 hours preceding testing or has a known preexisting muscular disease,
  • If the patient has a recent history of variceal bleeding,
  • If the patient is excessively sedated or mentally obtunded as judged by an inability to follow verbal commands.
  • We will not study pregnant females, prisoners, or institutionalized decisionally impaired patients.
Both
18 Years and older
No
Contact: Gerald Supinski, MD 859-494-3480 gsupi2@email.uky.edu
Contact: Leigh Ann Callahan, MD 7062311769 lacall2@email.uky.edu
United States
 
NCT01270516
Diaphragm EPA HMB
Yes
Gerald Supinski, University of Kentucky
University of Kentucky
Not Provided
Principal Investigator: Gerald Supinski, MD University of Kentucky
University of Kentucky
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP